Marcia L. Stefanick, Ph.D.

All Publications

• Stratified Probabilistic Bias Analysis for Body Mass Index-related Exposure Misclassification in Postmenopausal Women EPIDEMIOLOGY Banack, H. R., Stokes, A., Fox, M. P., Hovey, K. M., Feliciano, E., LeBlanc, E. S., Bird, C., Caan, B. J., Kroenke, C. H., Allison, M. A., Going, S. B., Snetselaar, L., Cheng, T., Chlebowski, R. T., Stefanick, M. L., LaMonte, M. J., Wactawski-Wende, J. 2018; 29 (5): 604–13

  Abstract

  There is widespread concern about the use of body mass index (BMI) to define obesity status in postmenopausal women because it may not accurately represent an individual's true obesity status. The objective of the present study is to examine and adjust for exposure misclassification bias from using an indirect measure of obesity (BMI) compared with a direct measure of obesity (percent body fat).We used data from postmenopausal non-Hispanic black and non-Hispanic white women in the Women's Health Initiative (n=126,459). Within the Women's Health Initiative, a sample of 11,018 women were invited to participate in a sub-study involving dual-energy x-ray absorptiometry scans. We examined indices of validity comparing BMI-defined obesity (≥30 kg/m), with obesity defined by percent body fat. We then used probabilistic bias analysis models stratified by age and race to explore the effect of exposure misclassification on the obesity-mortality relationship.Validation analyses highlight that using a BMI cutpoint of 30 kg/m to define obesity in postmenopausal women is associated with poor validity. There were notable differences in sensitivity by age and race. Results from the stratified bias analysis demonstrated that failing to adjust for exposure misclassification bias results in attenuated estimates of the obesity-mortality relationship. For example, in non-Hispanic white women 50-59 years of age, the conventional risk difference was 0.017 (95% confidence interval = 0.01, 0.023) and the bias-adjusted risk difference was 0.035 (95% simulation interval = 0.028, 0.043).These results demonstrate the importance of using quantitative bias analysis techniques to account for nondifferential exposure misclassification of BMI-defined obesity. See video abstract at, http://links.lww.com/EDE/B385.

  View details for DOI 10.1097/EDE.0000000000000863

  View details for Web of Science ID 000441143500010

  View details for PubMedID 29864084

• 27-hydroxycholesterol, an endogenous SERM, and risk of fracture in postmenopausal women: A nested case-cohort study in the Women's Health Initiative. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Chang, P., Feldman, D., Stefanick, M. L., McDonnell, D. P., Thompson, B. M., McDonald, J. G., Lee, J. S. 2018

  Abstract

  27-hydroxycholesterol (27HC) is a purported, novel endogenous SERM. In animal models, 27HC has an anti-estrogen effect in bone, and 17beta-estradiol mitigates this effect. 27HC in relation to fracture risk has not been investigated in humans. Depending on the level of bioavailable 17beta-estradiol (bioE2), 27HC may increase fracture risk in postmenopausal women and modify the fracture risk reduction from menopausal hormone therapy (MHT). To test these a priori hypotheses, we conducted a nested case-cohort study of 868 postmenopausal women within the Women's Health Initiative Hormone Therapy trials (WHI-HT). The WHI-HT tested conjugated equine estrogens versus placebo and separately conjugated equine estrogens plus progestin versus placebo. Fracture cases were 442 women who had an adjudicated incident hip or clinical vertebral fracture during the WHI-HT follow-up. The sub-cohort included 430 women randomly selected at WHI-HT baseline, 4 of whom had a subsequent fracture. Of 868 women, 266 cases and 219 non-cases were assigned to the placebo arms. Cox models estimated hazard ratios for incident fracture in relation to pre-randomization circulating levels of 27HC and 27HC/bioE2 molar ratio. Models adjusted for age, race/ethnicity, total cholesterol, bioE2, sex hormone-binding globulin, 25-hydroxyvitamin D, diabetes, osteoporosis, prior MHT use, BMI, falls history and prior fracture. In women assigned to placebo arms, those in the middle and the highest tertiles of 27HC/bioE2 had an up to 1.9-fold (95% confidence intervals: 1.25-2.99) greater risk of fracture than women in the lowest tertile. In women assigned to MHT arms, fracture risk increased with continuous 27HC/bioE2 levels but not with categorical levels. 27HC levels alone were not associated with fracture risk. 27HC and 27HC/bioE2 did not modify the fracture risk reduction from MHT. In postmenopausal women, circulating levels of 27HC relative to bioE2 may identify those at increased risk of fracture. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbmr.3576

  View details for PubMedID 30138538

• Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women INTERNATIONAL JOURNAL OF CANCER Kabat, G. C., Kim, M. Y., Stefanick, M., Ho, G. F., Lane, D. S., Odegaard, A. O., Simon, M. S., Bea, J. W., Luo, J., Wassertheil-Smoller, S., Rohan, T. E. 2018; 143 (3): 543–51

  Abstract

  Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2 ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.

  View details for DOI 10.1002/ijc.31345

  View details for Web of Science ID 000436110100011

  View details for PubMedID 29488210

• Association between physical health and cardiovascular diseases: Effect modification by chronic conditions SAGE OPEN MEDICINE Saquib, N., Brunner, R., Desai, M., Allison, M., Garcia, L., Stefanick, M. L. 2018; 6: 2050312118785335

  Abstract

  This study assessed whether the physical component summary score of the RAND-36 health-related quality-of-life survey was associated with incidence of coronary heart disease, stroke, congestive heart failure, angina, or peripheral arterial disease, and whether baseline chronic conditions modified these associations.Analysis was limited to 69,155 postmenopausal women (50-79 years) in the Women's Health Initiative Study who had complete data on the RAND-36, the outcomes, and covariates. Chronic conditions were defined as blood pressure ⩾140/90 mm or self-reported heart disease, diabetes, hypertension, arthritis, asthma, emphysema, cancer, and/or cholesterol-reducing medication use. Outcomes data were ascertained during follow-up (1993-2005) with medical records.There were 2451 coronary heart disease, 1896 stroke, 1533 congestive heart failure, 1957 angina, and 502 peripheral arterial disease events during follow-up (median 8.2 years). Participants in the lowest physical component summary quintile, compared to the highest, had a significantly higher risk of developing coronary heart disease (hazard ratio (95% confidence interval) 2.0 (1.7, 2.3)), stroke (1.8 (1.5, 2.2)), angina (2.4(2.0, 2.9)), and peripheral arterial disease (3.0 (2.0, 4.4)), irrespective of chronic conditions. Interactions between physical component summary and existing chronic conditions were not significant for any outcome except congestive heart failure (p = 0.005); after adjustment, participants in the lowest physical component summary quintile and with any chronic condition had nearly a twofold higher risk of congestive heart failure (Yes = 4.4 (3.3, 5.8) vs No = 2.4 (1.2, 4.3)).We found a low physical component summary score was a significant risk factor for individual cardiovascular disease incidence in postmenopausal women.

  View details for DOI 10.1177/2050312118785335

  View details for Web of Science ID 000438397500001

  View details for PubMedID 30013784

  View details for PubMedCentralID PMC6041849

• Association of 25-hydroxyvitamin D levels and cutaneous melanoma: A nested case-control study of the Women's Health Initiative Observation Study. Journal of the American Academy of Dermatology Kwon, G. P., Gamba, C. S., Stefanick, M. L., Swetter, S. M., Li, S., Shi, R. Z., Clarke, C. A., Feldman, D., Millen, A. E., Messina, C., Shikany, J. M., Manson, J. E., Chlebowski, R. T., Tang, J. Y. 2018; 79 (1): 145–47

  View details for DOI 10.1016/j.jaad.2017.05.037

  View details for PubMedID 29908819

• Effects of oral conjugated equine estrogens with or without medroxyprogesterone acetate on incident hypertension in the Women's Health Initiative hormone therapy trials MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Swica, Y., Warren, M. P., Manson, J. E., Aragaki, A. K., Bassuk, S. S., Shimbo, D., Kaunitz, A., Rossouw, J., Stefanick, M. L., Womack, C. R. 2018; 25 (7): 753–61

  Abstract

  The aim of the study was to determine the effect of menopausal hormone therapy on incident hypertension in the two Women's Health Initiative hormone therapy trials and in extended postintervention follow-up.A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. This analysis includes the subsample of 18,015 women who did not report hypertension at baseline and were not taking antihypertensive medication. Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 5,994) or placebo (n = 5,679). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 3,108) or placebo (n = 3,234). The intervention lasted a median of 5.6 years in the CEE plus MPA trial and 7.2 years in the CEE-alone trial with 13 years of cumulative follow-up until September 30, 2010. The primary outcome for these analyses was self-report of a new diagnosis of hypertension and/or high blood pressure requiring treatment with medication.During the CEE and CEE plus MPA intervention phase, the rate of incident hypertension was 18% higher for intervention than for placebo (CEE: hazard ratio [HR], 1.18; 95% CI, 1.09-1.29; CEE plus MPA: HR, 1.18; 95% CI, 1.09-1.27). This effect dissipated postintervention in both trials (CEE: HR, 1.06; 95% CI, 0.94-1.20; CEE plus MPA: HR, 1.02; 95% CI, 0.94-1.10).CEE (0.625 mg/d) administered orally, with or without MPA, is associated with an increased risk of hypertension in older postmenopausal women. Whether lower doses, different estrogen formulations, or transdermal route of administration offer lower risks warrant further study.

  View details for DOI 10.1097/GME.0000000000001067

  View details for Web of Science ID 000442315700008

  View details for PubMedID 29381666

  View details for PubMedCentralID PMC6014860

• Cognitive Function and Changes in Cognitive Function as Predictors of Incident Cardiovascular Disease: The Women's Health Initiative Memory Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Leng, X., Espeland, M. A., Manson, J. E., Stefanick, M. L., Gower, E. W., Hayden, K. M., Limacher, M. C., Vaughan, L., Robinson, J., Wallace, R., Wassertheil-Smoller, S., Yaffe, K., Shumaker, S. A. 2018; 73 (6): 779–85

  Abstract

  Cognitive impairment and decline may signal the increased risk of incident cardiovascular disease (CVD). We examined associations of global cognitive function, as measured by the Modified Mini-Mental State Examination (3MS) and changes in 3MS over time, with incident CVD, individual CVD outcomes, CVD death, and all-cause mortality.A total of 5,596 women (≥ 60) from the Women's Health Initiative Memory Study free of CVD at baseline were followed for an average of 7.1 years. The 3MS was measured at baseline and annually thereafter. Cox proportional hazards regressions were used to model associations between baseline 3MS and changes in 3MS and time to events.In the fully-adjusted models for every 5-point lower baseline 3MS score, the risk was 12% greater for incident CVD, 37% for HF, 35% for CVD death, and 24% for all-cause mortality. No significant relationships were found for coronary heart disease (CHD), angina, stroke/transient ischemic attack (TIA), or coronary revascularization. When change in 3MS was added as a time-varying covariate in the fully-adjusted models, for every 1-point/year greater decline in 3MS, the risk was 4% greater for incident CVD, 10% for CHD, 9% for Stroke/TIA, 17% for CVD death, and 13% for all-cause mortality.In older women free of prevalent CVD at baseline, lower baseline global cognitive function or decline in global cognitive function over time, increased risk of incident CVD, CVD death, and all-cause mortality.

  View details for DOI 10.1093/gerona/glx138

  View details for Web of Science ID 000432279700010

  View details for PubMedID 28977360

  View details for PubMedCentralID PMC5946937

• Predictors of vasomotor symptoms among breast cancer survivors JOURNAL OF CANCER SURVIVORSHIP Reeves, K. W., Pennell, M., Foraker, R. E., Crandall, C. J., Stefanick, M., Paskett, E. D. 2018; 12 (3): 379–87

  Abstract

  Vasomotor symptoms (VMS) are a common side effect of breast cancer treatment, yet modifiable factors that may predict VMS among breast cancer survivors are unknown.We estimated multivariable-adjusted odds ratios and 95% confidence intervals (aOR, 95% CI) for predictors of VMS among 3595 breast cancer survivors enrolled in the Life and Longevity after Cancer (LILAC) study, an ancillary study of the Women's Health Initiative (WHI).VMS post-diagnosis were reported by 790 (22.0%) participants. Risk of VMS after diagnosis was positively associated with prior chemotherapy (aOR 1.80, 95% CI 1.21-2.68) and adjuvant hormone therapy (aOR 2.73, 95% CI 2.08-3.58), postmenopausal hormone therapy use (aOR 1.67, 95% CI 1.30-2.13), prior VMS (aOR 2.20, 95% CI 1.73-2.80), bilateral oophorectomy (aOR 1.77, 95% CI 1.37-2.27), and baseline antidepressant use (aOR 1.49, 1.06-2.09). VMS post-diagnosis were less likely among younger women (aOR 0.94, 95% CI 0.93-0.96), women younger at menopause (aOR 0.98, 95% CI 0.97-1.00), women with more time since diagnosis (aOR 0.92, 95% CI 0.90-0.94), and diabetics (aOR 0.45, 95% CI 0.21-0.95). Metabolic syndrome was not associated with post-diagnosis VMS (aOR 0.76, 95% CI 0.45-1.28).VMS following breast cancer diagnosis was related to a number of modifiable factors, but was unrelated to metabolic syndrome.Identification of factors that predispose women to VMS following a breast cancer diagnosis may allow clinicians to recognize and address VMS in the subset of women who are most likely to experience such symptoms.

  View details for DOI 10.1007/s11764-018-0677-9

  View details for Web of Science ID 000432533200010

  View details for PubMedID 29427202

  View details for PubMedCentralID PMC5955842

• Accelerometer-Measured Physical Activity and Mortality in Women Aged 63 to 99 JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LaMonte, M. J., Buchner, D. M., Rillamas-Sun, E., Di, C., Evenson, K. R., Bellettiere, J., Lewis, C. E., Lee, I., Tinker, L. F., Seguin, R., Zaslovsky, O., Eaton, C. B., Stefanick, M. L., LaCroix, A. Z. 2018; 66 (5): 886–94

  Abstract

  To prospectively examine associations between accelerometer-measured physical activity (PA) and mortality in older women, with an emphasis on light-intensity PA.Prospective cohort study with baseline data collection between March 2012 and April 2014.Women's Health Initiative cohort in the United States.Community-dwelling women aged 63 to 99 (N = 6,382).Minutes per day of usual PA measured using hip-worn triaxial accelerometers, physical functioning measured using the Short Physical Performance Battery, mortality follow-up for a mean 3.1 years through September 2016 (450 deaths).When adjusted for accelerometer wear time, age, race-ethnicity, education, smoking, alcohol, self-rated health, and comorbidities, relative risks (95% confidence intervals) for all-cause mortality across PA tertiles were 1.00 (referent), 0.86 (0.69, 1.08), 0.80 (0.62, 1.03) trend P = .07, for low light; 1.00, 0.57 (0.45, 0.71), 0.47 (0.35, 0.61) trend P < .001, for high light; and, 1.00, 0.63 (0.50, 0.79), 0.42 (0.30, 0.57) trend P < .001, for moderate-to-vigorous PA (MVPA). Associations remained significant for high light-intensity PA and MVPA (P < .001) after further adjustment for physical function. Each 30-min/d increment in light-intensity (low and high combined) PA and MVPA was associated, on average, with multivariable relative risk reductions of 12% and 39%, respectively (P < .01). After further simultaneous adjusting for light intensity and MVPA, the inverse associations remained significant (light-intensity PA: RR = 0.93, 95% CI = 0.89-0.97; MVPA: RR = 0.67, 95% CI = 0.58-0.78). These relative risks did not differ between subgroups for age or race and ethnicity (interaction, P ≥ .14, all).When measured using accelerometers, light-intensity and MVPA are associated with lower mortality in older women. These findings suggest that replacing sedentary time with light-intensity PA is a public health strategy that could benefit an aging society and warrants further investigation.

  View details for DOI 10.1111/jgs.15201

  View details for Web of Science ID 000433585500009

  View details for PubMedID 29143320

  View details for PubMedCentralID PMC5955801

• Impact of hormone therapy on Medicare spending in the Women's Health Initiative randomized clinical trials AMERICAN HEART JOURNAL Shreibati, J. B., Manson, J. E., Margolis, K. L., Chlebowski, R. T., Stefanick, M. L., Hlatky, M. A. 2018; 198: 108–14

  Abstract

  Randomized trials can compare economic as well as clinical outcomes, but economic data are difficult to collect. Linking clinical trial data with Medicare claims could provide novel information on health care utilization and cost.We linked data from Medicare claims of women ≥65 years old who had Medicare fee-for-service coverage with their clinical data from the Women's Health Initiative trials of conjugated equine estrogens plus medroxyprogesterone acetate (CEE+MPA) versus placebo and of CEE-alone versus placebo. The primary outcome was total Medicare spending during the intervention phase of the trial, and the secondary outcomes were spending on diseases hypothesized a priori to be sensitive to the effects of hormone therapy.In the CEE+MPA trial, 4,557 participants ≥65 years old were included. Women randomly assigned to CEE+MPA had 4% higher mean Medicare spending overall ($45,690 vs $43,920, P = .08) but 0.5% lower spending for hormone-sensitive diseases ($3,526 vs $3,547, P = .07), with 73% higher spending for coronary heart disease (P = .045) and 122% higher spending for pulmonary embolism (P = .026). In the CEE-alone trial, 3,107 participants were included. Total spending among women randomly assigned to CEE was 3.3% higher ($75,411 vs $72,997, P = .16), and 1.7% higher spending for hormone-sensitive diseases ($5,213 vs $5,127, P = .57), but with 39% lower spending for hip fracture (p<0.03).Menopausal hormone therapy increased spending for some diseases, but decreased spending for others. These offsetting effects led to modest (3%-4%), nonsignificant increases in overall spending among women aged 65 years and older.

  View details for DOI 10.1016/j.ahj.2017.12.016

  View details for Web of Science ID 000430004300014

  View details for PubMedID 29653631

  View details for PubMedCentralID PMC5901884

• 36-Item Short Form Survey (SF-36) Versus Gait Speed As Predictor of Preclinical Mobility Disability in Older Women: The Women's Health Initiative JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Laddu, D. R., Wertheim, B. C., Garcia, D. O., Woods, N. F., LaMonte, M. J., Chen, B., Anton-Culver, H., Zaslavsky, O., Cauley, J. A., Chlebowski, R., Manson, J. E., Thomson, C. A., Stefanick, M. L., Womens Hlth Initiative Investigato 2018; 66 (4): 706–13

  Abstract

  To compare the value of clinically measured gait speed with that of the self-reported Medical Outcomes Study 36-item Short-Form Survey Physical Function Index (SF-36 PF) in predicting future preclinical mobility disability (PCMD) in older women.Prospective cohort study.Forty clinical centers in the United States.Women aged 65 to 79 enrolled in the Women's Health Initiative Clinical Trials with gait speed and SF-36 assessed at baseline (1993-1998) and follow-up Years 1, 3, and 6 (N = 3,587).Women were categorized as nondecliners or decliners based on changes (from baseline to Year 1) in gait speed and SF-36 PF scores. Logistic regression models were used to estimate incident PCMD (gait speed <1.0 m/s) at Years 3 and 6. Area under the receiver operating characteristic curve (AUC) was used to compare the predictive value of SF-36 PF with that of measured gait speed.Slower baseline gait speed and lower SF-36 PF scores were associated with higher adjusted odds of PCMD at Years 3 and 6 (all P < .001). For gait speed, decliners were 2.59 times as likely to have developed PCMD as nondecliners by Year 3 and 2.35 times as likely by Year 6. Likewise, for SF-36, decliners were 1.42 times as likely to have developed PCMD by Year 3 and 1.49 times as likely by Year 6. Baseline gait speed (AUC = 0.713) was nonsignificantly better than SF-36 (AUC = 0.705) at predicting PCMD over 6 years (P = .21); including measures at a second time point significantly improved model discrimination for predicting PCMD (all P < .001).Gait speed identified PCMD risk in older women better than the SF-36 PF did, although the results may be limited given that gait speed served as a predictor and to define the PCMD outcome. Nonetheless, monitoring trajectories of change in mobility are better predictors of future mobility disability than single measures.

  View details for DOI 10.1111/jgs.15273

  View details for Web of Science ID 000430300800012

  View details for PubMedID 29427503

  View details for PubMedCentralID PMC5906155

• Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project BRITISH JOURNAL OF CANCER Petrick, J. L., Campbell, P. T., Koshiol, J., Thistle, J. E., Andreotti, G., Beane-Freeman, L. E., Buring, J. E., Chan, A. T., Chong, D. Q., Doody, M. M., Gapstur, S. M., Gaziano, J., Giovannucci, E., Graubard, B. I., Lee, I., Liao, L. M., Linet, M. S., Palmer, J. R., Poynter, J. N., Purdue, M. P., Robien, K., Rosenberg, L., Schairer, C., Sesso, H. D., Sinha, R., Stampfer, M. J., Stefanick, M., Wactawski-Wende, J., Zhang, X., Zeleniuch-Jacquotte, A., Freedman, N. D., McGlynn, K. A. 2018; 118 (7): 1005–12

  Abstract

  While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression.Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR≥7 drinks/day = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR≥5 drinks/day = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR>0-<0.5 drinks/day = 0.77, 95% CI: 0.67-0.89; HR>0.5-<1 drinks/day = 0.57, 95% CI: 0.44-0.73; HR1-<3 drinks/day = 0.71, 95% CI: 0.58-0.87), but not ICC.These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

  View details for DOI 10.1038/s41416-018-0007-z

  View details for Web of Science ID 000429279300011

  View details for PubMedID 29520041

  View details for PubMedCentralID PMC5931109

• Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort. Journal of the American Academy of Dermatology Cho, H. G., Ransohoff, K. J., Yang, L., Hedlin, H., Assimes, T., Han, J., Stefanick, M., Tang, J. Y., Sarin, K. Y. 2018

  Abstract

  BACKGROUND: Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk.OBJECTIVE: We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.METHODS: Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset.RESULTS: Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma.LIMITATIONS: Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort.CONCLUSION: Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.

  View details for DOI 10.1016/j.jaad.2018.02.052

  View details for PubMedID 29499294

• Osteoarthritis and Reproductive History in the Women's Health Initiative. Wang, A., Zawadzki, N., Hedlin, H., Desai, M., Westphal, L., Stefanick, M. L. SAGE PUBLICATIONS INC. 2018: 87A

  View details for Web of Science ID 000429928200092

• Weight change in postmenopausal women and breast cancer risk in the women's health initiative observational study Chlebowski, R. T., Luo, J., Anderson, G. L., Simon, M., Barrington, W., Reding, K., Manson, J. E., Rohan, T., Wactawki-Wende, J., Lane, D., Strickler, H., Mossavar-Rahmani, Y., Freudenheim, J., Saquib, A., Stefanick, M. AMER ASSOC CANCER RESEARCH. 2018

  View details for Web of Science ID 000425489400035

• Menopausal Hormone Therapy and Long-Term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials OBSTETRICAL & GYNECOLOGICAL SURVEY Manson, J. E., Aragaki, A. K., Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Chlebowski, R. T., Howard, B. V., Thomson, C. A., Margolis, K. L., Lewis, C. E., Stefanick, M. L., Jackson, R. D., Johnson, K. C., Martin, L. W., Shumaker, S. A., Espeland, M. A., Wactawski-Wende, J., WHI Investigators 2018; 73 (1): 22–24

  View details for DOI 10.1097/01.ogx.0000527868.87744.14

  View details for Web of Science ID 000423437700012

• Potential Reporting Bias in Neuroimaging Studies of Sex Differences. Scientific reports David, S. P., Naudet, F., Laude, J., Radua, J., Fusar-Poli, P., Chu, I., Stefanick, M. L., Ioannidis, J. P. 2018; 8 (1): 6082

  Abstract

  Numerous functional magnetic resonance imaging (fMRI) studies have reported sex differences. To empirically evaluate for evidence of excessive significance bias in this literature, we searched for published fMRI studies of human brain to evaluate sex differences, regardless of the topic investigated, in Medline and Scopus over 10 years. We analyzed the prevalence of conclusions in favor of sex differences and the correlation between study sample sizes and number of significant foci identified. In the absence of bias, larger studies (better powered) should identify a larger number of significant foci. Across 179 papers, median sample size was n = 32 (interquartile range 23-47.5). A median of 5 foci related to sex differences were reported (interquartile range, 2-9.5). Few articles (n = 2) had titles focused on no differences or on similarities (n = 3) between sexes. Overall, 158 papers (88%) reached "positive" conclusions in their abstract and presented some foci related to sex differences. There was no statistically significant relationship between sample size and the number of foci (-0.048% increase for every 10 participants, p = 0.63). The extremely high prevalence of "positive" results and the lack of the expected relationship between sample size and the number of discovered foci reflect probable reporting bias and excess significance bias in this literature.

  View details for DOI 10.1038/s41598-018-23976-1

  View details for PubMedID 29666377

• Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Crandall, C. J., Hovey, K. M., Andrews, C. A., Chlebowski, R. T., Stefanick, M. L., Lane, D. S., Shifren, J., Chen, C., Kaunitz, A. M., Cauley, J. A., Manson, J. E. 2018; 25 (1): 11–20

  View details for DOI 10.1097/GME.0000000000000956

  View details for Web of Science ID 000429318200005

• Risk of cardiovascular disease among women with endometrial cancer compared to cancer-free women in the Women's Health Initiative CANCER EPIDEMIOLOGY Felix, A. S., Lehman, A., Foraker, R. E., Naughton, M. J., Bower, J. K., Kuller, L., Sarto, G. E., Stefanick, M. L., Van Horn, L., Jackson, R. D., Paskett, E. D. 2017; 51: 62–67

  Abstract

  The majority of women diagnosed with endometrial cancer (EC) have low cancer-specific mortality; however, a high prevalence of cardiovascular disease (CVD) risk factors places EC patients at high risk of developing CVD. In the Women's Health Initiative (WHI), we assessed the hypothesis that CVD risk was higher among women who developed EC compared with women who did not develop EC.We compared the incidence of fatal and non-fatal CVD events among 1,179 women who developed Type I EC, 211 women who developed Type II EC, and 92,217 women who did not develop EC. We first estimated univariable cause-specific hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association between an EC diagnosis (overall and by EC type) with CVD risk using Cox proportional hazards regression. Potential confounders were examined using a risk factor modeling approach; final multivariable-adjusted models included covariates that changed univariable CHRs for EC diagnosis by≥5%.In multivariable-adjusted models, CVD risk did not significantly differ between women who developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87-1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98, 95% CI=0.84-1.14); however, there was a positive but statistically nonsignificant association for Type II EC (CHR=1.32, 95% CI=0.88-1.97).Despite our null findings, women with EC should still receive counseling and support to make lifestyle changes aimed at reducing weight as appropriate, given the high prevalence of CVD risk factors at diagnosis.

  View details for DOI 10.1016/j.canep.2017.10.009

  View details for Web of Science ID 000415839800011

  View details for PubMedID 29049937

  View details for PubMedCentralID PMC5700837

• Breast Cancer, Endometrial Cancer, and Cardiovascular Events in Participants who used Vaginal Estrogen in the WHI Observational Study Crandall, C. J., Hovey, K., Andrews, C., Chlebowski, R., Stefanick, M., Lane, D., Shifren, J., Chen, C., Kaunitz, A., Cauley, J., Manson, J. LIPPINCOTT WILLIAMS & WILKINS. 2017: 1423–24

  View details for Web of Science ID 000423298900039

• Sedentary time and postmenopausal breast cancer incidence CANCER CAUSES & CONTROL Nomura, S. O., Dash, C., Sheppard, V. B., Bowen, D., Allison, M., Barrington, W., Chlebowski, R., Coday, M., Hou, L., Howard, B., LaMonte, M., Manson, J. E., Neuhouser, M. L., Paskett, E., Sattari, M., Stefanick, M., Wactawski-Wende, J., Adams-Campbell, L. L. 2017; 28 (12): 1405–16

  Abstract

  The objective of this study was to evaluate the prospective association between sedentary time and postmenopausal breast cancer incidence, and whether associations differ by race/ethnicity, physical activity levels, and body measurements.The Women's Health Initiative Observational Study is a prospective cohort among women ages 50-79 years at baseline (1994-1998) (analytic cohort = 70,233). Baseline questionnaire data were used to estimate time spent sitting and total sedentary time. Associations between time spent sitting and invasive breast cancer incidence overall (n = 4,115 cases through September 2015), and by hormone receptor subtypes, were investigated using Cox proportional hazards regression. Analyses were replicated stratified by race/ethnicity, body measurements, and physical activity.Among women in this study, 34.5% reported ≤ 5 h/day sitting, 40.9% reported 6-9 h/day and 24.7% reported ≥ 10 h/day. Time spent sitting (≥ 10 vs. ≤5 h/day adjusted HR = 1.00, 95% CI 0.92-1.09) was not associated with breast cancer incidence, regardless of hormone receptor subtype. Associations did not differ by race/ethnicity, physical activity, or body measurements.Results from this study do not support an association between sedentary time and breast cancer incidence.

  View details for DOI 10.1007/s10552-017-0968-x

  View details for Web of Science ID 000415357700005

  View details for PubMedID 28975422

  View details for PubMedCentralID PMC5687985

• Associations of Biomarker-Calibrated Sodium and Potassium Intakes With Cardiovascular Disease Risk Among Postmenopausal Women AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Huang, Y., Neuhouser, M. L., Manson, J. E., Mossavar-Rahmani, Y., Thomas, F., Tinker, L. F., Allison, M., Johnson, K. C., Wassertheil-Smoller, S., Seth, A., Rossouw, J. E., Shikany, J., Carbone, L. D., Martin, L. W., Stefanick, M. L., Haring, B., Van Horn, L. 2017; 186 (9): 1035–43

  Abstract

  Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium.

  View details for DOI 10.1093/aje/kwx238

  View details for Web of Science ID 000414354000004

  View details for PubMedID 28633342

  View details for PubMedCentralID PMC5860327

• Accelerometer-Measured Moderate to Vigorous Physical Activity and Incidence Rates of Falls in Older Women JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Buchner, D. M., Rillamas-Sun, E., Di, C., LaMonte, M. J., Marshall, S. W., Hunt, J., Zhang, Y., Rosenberg, D. E., Lee, I., Evenson, K. R., Herring, A. H., Lewis, C. E., Stefanick, M. L., LaCroix, A. Z. 2017; 65 (11): 2480–87

  Abstract

  To examine whether moderate to vigorous physical activity (MVPA) measured using accelerometry is associated with incident falls and whether associations differ according to physical function or history of falls.Prospective study with baseline data collection from 2012 to 2014 and 1 year of follow-up.Women's Health Initiative participants living in the United States.Ambulatory women aged 63 to 99 (N = 5,545).Minutes of MVPA per day measured using an accelerometer, functional status measured using the Short Physical Performance Battery (SPPB), fall risk factors assessed using a questionnaire, fall injuries assessed in a telephone interview, incident falls ascertained from fall calendars.Incident rate ratios (IRRs) revealed greater fall risk in women in the lowest quartile of MVPA compared to those in the highest (IRR = 1.18, 95% confidence interval = 1.01-1.38), adjusted for age, race and ethnicity, and fall risk factors. Fall rates were not significantly associated with MVPA in women with high SPPB scores (9-12) or one or fewer falls in the previous year, but in women with low SPPB scores (≤ 8) or a history of frequent falls, fall rates were higher in women with lower MVPA levels than in those with higher levels (interaction P < .03 and < .001, respectively). Falls in women with MVPA above the median were less likely to involve injuries requiring medical treatment (9.9%) than falls in women with lower MVPA levels (13.0%) (P < .001).These findings indicate that falls are not more common or injurious in older women who engage in higher levels of MVPA. These findings support encouraging women to engage in the amounts and types of MVPA that they prefer. Older women with low physical function or frequent falls with low levels of MVPA are a high-risk group for whom vigilance about falls prevention is warranted.

  View details for DOI 10.1111/jgs.14960

  View details for Web of Science ID 000417766900024

  View details for PubMedID 28755415

  View details for PubMedCentralID PMC5681400

• Both Light Intensity and Moderate-to-Vigorous Physical Activity Measured by Accelerometry Are Favorably Associated With Cardiometabolic Risk Factors in Older Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study JOURNAL OF THE AMERICAN HEART ASSOCIATION LaMonte, M. J., Lewis, C. E., Buchner, D. M., Evenson, K. R., Rillamas-Sun, E., Di, C., Lee, I., Bellettiere, J., Stefanick, M. L., Eaton, C. B., Howard, B. V., Bird, C., LaCroix, A. Z. 2017; 6 (10)

  View details for DOI 10.1161/JAHA.117.007064

  View details for Web of Science ID 000418940300076

• Metabolic Syndrome Does Not Modify the Association between Obesity and Hip Osteoarthritis Cheng, K., Ball, S., Schenk, S., Strotmeyer, E., Schousboe, J., Stefanick, M., Barrett-Connor, E., Kado, D., Nevitt, M., Lane, N. E., Orwoll, E., Hughes-Austin, J. M. WILEY. 2017

  View details for Web of Science ID 000411824105022

• Obesity and Falls in a Prospective Study of Older Men: The Osteoporotic Fractures in Men Study JOURNAL OF AGING AND HEALTH Hooker, E. R., Shrestha, S., Lee, C. G., Cawthon, P. M., Abrahamson, M., Ensrud, K., Stefanick, M. L., Dam, T., Marshall, L. M., Orwoll, E. S., Nielson, C. M., Osteoporotic Fractures Men MrOS St 2017; 29 (7): 1235–50

  Abstract

  The aim of this study is to evaluate fall rates across body mass index (BMI) categories by age group, considering physical performance and comorbidities.In the Osteoporotic Fractures in Men (MrOS) study, 5,834 men aged ≥65 reported falls every 4 months over 4.8 (±0.8) years. Adjusted associations between BMI and an incident fall were tested using mixed-effects models.The fall rate (0.66/man-year overall, 95% confidence interval [CI] = [0.65, 0.67]) was lowest in the youngest, normal weight men (0.44/man-year, 95% CI = [0.41, 0.47]) and greatest in the oldest, highest BMI men (1.47 falls/man-year, 95% CI = [1.22, 1.76]). Obesity was associated with a 24% to 92% increased fall risk in men below 80 ( ptrend ≤ .0001, p for interaction by age = .03). Only adjustment for dynamic balance test altered the BMI-falls association substantially.Obesity was independently associated with higher fall rates in men 65 to 80 years old. Narrow walk time, a measure of gait stability, may mediate the association.

  View details for DOI 10.1177/0898264316660412

  View details for Web of Science ID 000418259500006

  View details for PubMedID 27469600

  View details for PubMedCentralID PMC5773405

• Associations Between Self-Reported Physical Activity and Physical Performance Measures Over Time in Postmenopausal Women: The Women's Health Initiative JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Laddu, D. R., Wertheim, B. C., Garcia, D. O., Brunner, R., Groessl, E., Shadyab, A. H., Going, S. B., LaMonte, M. J., Cannell, B., LeBoff, M. S., Cauley, J. A., Thomson, C. A., Stefanick, M. L. 2017; 65 (10): 2176–81

  Abstract

  To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women.Prospective cohort study.Forty clinical centers in the United States.Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993-98) and follow-up Years 1, 3, and 6 (N = 5,092).Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (<70, ≥70) were also tested.Significan, dose-response associations between PA and improvements in all PPMs were observed over the 6 years of follow-up after adjusting for important covariates. High PA groups (≥1,200 metabolic equivalent (MET)-min/wk) had stronger grip strength (0.48 kg greater; P < .01), more chair stands (0.35 more; P < .001), and faster gait speeds (0.06 m/s faster; P < .001) than sedentary women (<100 MET-min/wk). Higher PA levels were associated with a greater increase in chair stands over time in women aged 70 and older (P < .001) than in those younger than 70 (Pinteraction for age  = .01).In postmenopausal women, maintaining high PA levels over time is associated with better lower extremity function. These data support the view that regular PA plays an important role in maintaining functional status during aging in older women.

  View details for DOI 10.1111/jgs.14991

  View details for Web of Science ID 000417650000013

  View details for PubMedID 28675421

  View details for PubMedCentralID PMC5641229

• Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality The Women's Health Initiative Randomized Trials JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Manson, J. E., Aragaki, A. K., Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Chlebowski, R. T., Howard, B. V., Thomson, C. A., Margolis, K. L., Lewis, C. E., Stefanick, M. L., Jackson, R. D., Johnson, K. C., Martin, L., Shumaker, S. A., Espeland, M. A., Wactawski-Wende, J., WHI Investigators 2017; 318 (10): 927–38

  Abstract

  Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.clinicaltrials.gov Identifier: NCT00000611.

  View details for DOI 10.1001/jama.2017.11217

  View details for Web of Science ID 000410487100014

  View details for PubMedID 28898378

  View details for PubMedCentralID PMC5728370

• Trajectories of the relationships of physical activity with body composition changes in older men: the MrOS study. BMC geriatrics Laddu, D. R., Cawthon, P. M., Parimi, N., Hoffman, A. R., Orwoll, E., Miljkovic, I., Stefanick, M. L. 2017; 17 (1): 119-?

  Abstract

  Excess adiposity gains and significant lean mass loss may be risk factors for chronic disease in old age. Long-term patterns of change in physical activity (PA) and their influence on body composition decline during aging has not been characterized. We evaluated the interrelationships of PA and body composition at the outset and over longitudinal follow-up to changes in older men.Self-reported PA by the Physical Activity Scale for the Elderly (PASE), clinic body weight, and whole-body lean mass (LM) and fat mass, by dual-energy x-ray absorptiometry (DXA), were assessed in 5964 community-dwelling men aged ≥65 years at baseline (2000-2002) and at two subsequent clinic visits up until March 2009 (an average 4.6 and 6.9 years later). Group-based trajectory modeling (GBTM) identified patterns of change in PA and body composition variables. Relationships of PA and body composition changes were then assessed.GBTM identified three discrete trajectory patterns, all with declining PA, associated primarily with initial PA levelshigh-activity (7.2% of men), moderate-activity (50.0%), and low-activity (42.8%). In separate models, GBTM identified eight discrete total weight change groups, five fat mass change groups, and six LM change groups. Joint trajectory modeling by PA and body composition group illustrated significant declines in total weight and LM, whereas fat mass levels were relatively unchanged among high-activity and low-activity-declining groups, and significantly increased in the moderate-activity-declining group.Although patterns of change in PA and body composition were identified, groups were primarily differentiated by initial PA or body composition rather than by distinct trajectories of change in these variables.

  View details for DOI 10.1186/s12877-017-0506-4

  View details for PubMedID 28583069

• Association of physical activity and sitting time with incident colorectal cancer in postmenopausal women. European journal of cancer prevention Gorczyca, A. M., Eaton, C. B., LaMonte, M. J., Garcia, D. O., Johnston, J. D., He, K., Bidulescu, A., Goodman, D., Groessl, E., Lane, D., Stefanick, M. L., Newcomb, P., Mouton, C., Chomistek, A. K. 2017

  Abstract

  Findings from epidemiological studies have found that physical activity (PA) is associated with a lower risk of colorectal cancer (CRC). Recent studies have found an increased CRC risk with higher sitting time (ST); however, many studies did not include PA as a potential confounder. The objective of this project was to investigate the independent and combined associations of ST and PA with the risk of incident CRC, specifically colon and rectal cancer. Participants in the Women's Health Initiative Observational Study (n=74 870), 50-79 years of age self-reported ST and PA at baseline, years 3 and 6. Incident CRC was the primary outcome; colon and rectal cancers were the secondary outcomes, which were centrally adjudicated. Over a 13-year follow-up period, 1145 incident cases of CRC were documented. A positive age-adjusted association was found between higher ST (≥10 vs. <5 h/day) and CRC (P for trend=0.04) and colon cancer (P for trend=0.05); however, these associations were attenuated and no longer significant in multivariable-adjusted models. Compared with inactive women (≤1.7 MET-h/week), the multivariable risk of CRC in the high PA (>20 MET-h/week) group was 0.81 (95% confidence interval: 0.66-1.00; P for trend 0.04). Compared with inactive women with high ST (≥10 h/day), there was a trend toward reduced multivariable CRC risks with higher PA irrespective of ST level (interaction=0.64). We observed an inverse association between leisure time PA and the risk of CRC, particularly for rectal cancer. There was no association between ST and CRC in multivariable models.

  View details for DOI 10.1097/CEJ.0000000000000351

  View details for PubMedID 28538039

• Evaluation of diet pattern and weight gain in postmenopausal women enrolled in the Women's Health Initiative Observational Study. British journal of nutrition Ford, C., Chang, S., Vitolins, M. Z., Fenton, J. I., Howard, B. V., Rhee, J. J., Stefanick, M., Chen, B., Snetselaar, L., Urrutia, R., Frazier-Wood, A. C. 2017: 1-10

  Abstract

  It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49-81 years (mean 63·6 (sd 7·4) years) from the Women's Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture's Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.

  View details for DOI 10.1017/S0007114517000952

  View details for PubMedID 28509665

• Change in Physical Activity and Sitting Time After Myocardial Infarction and Mortality Among Postmenopausal Women in the Women's Health Initiative-Observational Study. Journal of the American Heart Association Gorczyca, A. M., Eaton, C. B., LaMonte, M. J., Manson, J. E., Johnston, J. D., Bidulescu, A., Waring, M. E., Manini, T., Martin, L. W., Stefanick, M. L., He, K., Chomistek, A. K. 2017; 6 (5)

  Abstract

  How physical activity (PA) and sitting time may change after first myocardial infarction (MI) and the association with mortality in postmenopausal women is unknown.Participants included postmenopausal women in the Women's Health Initiative-Observational Study, aged 50 to 79 years who experienced a clinical MI during the study. This analysis included 856 women who had adequate data on PA exposure and 533 women for sitting time exposures. Sitting time was self-reported at baseline, year 3, and year 6. Self-reported PA was reported at baseline through year 8. Change in PA and sitting time were calculated as the difference between the cumulative average immediately following MI and the cumulative average immediately preceding MI. The 4 categories of change were: maintained low, decreased, increased, and maintained high. The cut points were ≥7.5 metabolic equivalent of task hours/week versus <7.5 metabolic equivalent of task hours/week for PA and ≥8 h/day versus <8 h/day for sitting time. Cox proportional hazard models estimated hazard ratios and 95% CIs for all-cause, coronary heart disease, and cardiovascular disease mortality. Compared with women who maintained low PA (referent), the risk of all-cause mortality was: 0.54 (0.34-0.86) for increased PA and 0.52 (0.36-0.73) for maintained high PA. Women who had pre-MI levels of sitting time <8 h/day, every 1 h/day increase in sitting time was associated with a 9% increased risk (hazard ratio=1.09, 95% CI: 1.01, 1.19) of all-cause mortality.Meeting the recommended PA guidelines pre- and post-MI may have a protective role against mortality in postmenopausal women.

  View details for DOI 10.1161/JAHA.116.005354

  View details for PubMedID 28507059

• Low Birth Weight and Risk of Later-Life Physical Disability in Women JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Spracklen, C. N., Ryckman, K. K., Robinson, J. G., Stefanick, M. L., Sarto, G. E., Anton, S. D., Wallace, R. B. 2017; 72 (4): 543–47

  Abstract

  There is strong evidence that low and high birth weight due to in-utero programming results in elevated risk for adult diseases, though less research has been performed examining the influence of birth weight and physical disability later in life.Baseline data from 76,055 postmenopausal women in the Women's Health Initiative, a large multi-ethnic cohort, were used to examine the association between self-reported birth weight category (<6 lbs, 6-7 lbs 15 oz, 8-9 lbs 15 oz, and ≥10 lbs) and the self-reported physical functioning score on the RAND 36-item Health Survey. Linear regression models were adjusted for age, education, race/ethnicity, body mass index, and a comorbidity score.Unadjusted models indicate that women born in the lowest and highest birth weight categories have significantly lower physical functioning scores as compared to women born in the normal weight category (β = -2.22, p < .0001 and β = -3.56, p < .0001, respectively). After adjustments, the relationship between the lowest birth weight category and physical functioning score remained significant (β = -1.52, p < .0001); however, the association with the highest birth weight category dissipated.Preconception and prenatal interventions aimed at reducing the incidence of low birth weight infants may subsequently reduce the burden of later-life physical disability.

  View details for DOI 10.1093/gerona/glw134

  View details for Web of Science ID 000402110100011

  View details for PubMedID 27440911

• The Associations of Atrial Fibrillation With the Risks of Incident Invasive Breast and Colorectal Cancers AMERICAN JOURNAL OF EPIDEMIOLOGY Wassertheil-Smoller, S., McGinn, A. P., Martin, L., Rodriguez, B. L., Stefanick, M. L., Perez, M. 2017; 185 (5): 372-384

  View details for DOI 10.1093/aje/kww185

  View details for Web of Science ID 000397245800007

• Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study JOURNAL OF BONE AND MINERAL RESEARCH Ensrud, K. E., Harrison, S. L., Cauley, J. A., Langsetmo, L., Schousboe, J. T., Kado, D. M., Gourlay, M. L., Lyons, J. G., Fredman, L., Napoli, N., Crandall, C. J., Lewis, C. E., Orwoll, E. S., Stefanick, M. L., Cawthon, P. M. 2017; 32 (3): 624-632

  View details for DOI 10.1002/jbmr.3020

  View details for Web of Science ID 000398055900022

• The Objective Physical Activity and Cardiovascular Disease Health in Older Women (OPACH) Study. BMC public health LaCroix, A. Z., Rillamas-Sun, E., Buchner, D., Evenson, K. R., Di, C., Lee, I., Marshall, S., LaMonte, M. J., Hunt, J., Tinker, L. F., Stefanick, M., Lewis, C. E., Bellettiere, J., Herring, A. H. 2017; 17 (1): 192-?

  Abstract

  Limited evidence exists to inform physical activity (PA) and sedentary behavior guidelines for older people, especially women. Rigorous evidence on the amounts, intensities, and movement patterns associated with better health in later life is needed.The Objective PA and Cardiovascular Health (OPACH) Study is an ancillary study to the Women's Health Initiative (WHI) Program that examines associations of accelerometer-assessed PA and sedentary behavior with cardiovascular and fall events. Between 2012 and 2014, 7048 women aged 63-99 were provided with an ActiGraph GT3X+ (Pensacola, Florida) triaxial accelerometer, a sleep log, and an OPACH PA Questionnaire; 6489 have accelerometer data. Most women were in their 70s (40%) or 80s (46%), while approximately 10% were in their 60s and 4% were age 90 years or older. Non-Hispanic Black or Hispanic/Latina women comprise half of the cohort. Follow-up includes 1-year of falls surveillance with monthly calendars and telephone interviews of fallers, and annual follow-up for outcomes with adjudication of incident cardiovascular disease (CVD) events through 2020. Over 63,600 months of calendar pages were returned by 5,776 women, who reported 5,980 falls. Telephone interviews were completed for 1,492 women to ascertain the circumstances, injuries and medical care associated with falling. The dataset contains extensive information on phenotypes related to healthy aging, including inflammatory and CVD biomarkers, breast and colon cancer, hip and other fractures, diabetes, and physical disability.This paper describes the study design, methods, and baseline data for a diverse cohort of postmenopausal women who wore accelerometers under free-living conditions as part of the OPACH Study. By using accelerometers to collect more precise and complete data on PA and sedentary behavior in a large cohort of older women, this study will contribute crucial new evidence about how much, how vigorous, and what patterns of PA are necessary to maintain optimal cardiovascular health and to avoid falls in later life.ClinicalTrials.gov identifier NCT00000611 . Registered 27 October 1999.

  View details for DOI 10.1186/s12889-017-4065-6

  View details for PubMedID 28193194

  View details for PubMedCentralID PMC5307783

• Intentional Weight Loss and Endometrial Cancer Risk. Journal of clinical oncology Luo, J., Chlebowski, R. T., Hendryx, M., Rohan, T., Wactawski-Wende, J., Thomson, C. A., Felix, A. S., Chen, C., Barrington, W., Coday, M., Stefanick, M., Leblanc, E., Margolis, K. L. 2017: JCO2016705822-?

  Abstract

  Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women's Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.

  View details for DOI 10.1200/JCO.2016.70.5822

  View details for PubMedID 28165909

• Metabolic Phenotype and Risk of Colorectal Cancer in Normal-Weight Postmenopausal Women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Liang, X., Margolis, K. L., Hendryx, M., Rohan, T. E., Groessl, E. J., Thomson, C. A., Kroenke, C. H., Simon, M. S., Lane, D., Stefanick, M., Luo, J. 2017; 26 (2): 155-161

  Abstract

  The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype.A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m(2) Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer.Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02-2.18) compared with those who were metabolically healthy.A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women.Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155-61. ©2017 AACR.

  View details for DOI 10.1158/1055-9965.EPI-16-0761

  View details for PubMedID 28148595

  View details for PubMedCentralID PMC5301805

• When a gold standard isn't so golden: Lack of prediction of subjective sleep quality from sleep polysomnography. Biological psychology Kaplan, K. A., Hirshman, J., Hernandez, B., Stefanick, M. L., Hoffman, A. R., Redline, S., Ancoli-Israel, S., Stone, K., Friedman, L., Zeitzer, J. M. 2017; 123: 37-46

  Abstract

  Reports of subjective sleep quality are frequently collected in research and clinical practice. It is unclear, however, how well polysomnographic measures of sleep correlate with subjective reports of prior-night sleep quality in elderly men and women. Furthermore, the relative importance of various polysomnographic, demographic and clinical characteristics in predicting subjective sleep quality is not known. We sought to determine the correlates of subjective sleep quality in older adults using more recently developed machine learning algorithms that are suitable for selecting and ranking important variables.Community-dwelling older men (n=1024) and women (n=459), a subset of those participating in the Osteoporotic Fractures in Men study and the Study of Osteoporotic Fractures study, respectively, completed a single night of at-home polysomnographic recording of sleep followed by a set of morning questions concerning the prior night's sleep quality. Questionnaires concerning demographics and psychological characteristics were also collected prior to the overnight recording and entered into multivariable models. Two machine learning algorithms, lasso penalized regression and random forests, determined variable selection and the ordering of variable importance separately for men and women.Thirty-eight sleep, demographic and clinical correlates of sleep quality were considered. Together, these multivariable models explained only 11-17% of the variance in predicting subjective sleep quality. Objective sleep efficiency emerged as the strongest correlate of subjective sleep quality across all models, and across both sexes. Greater total sleep time and sleep stage transitions were also significant objective correlates of subjective sleep quality. The amount of slow wave sleep obtained was not determined to be important.Overall, the commonly obtained measures of polysomnographically-defined sleep contributed little to subjective ratings of prior-night sleep quality. Though they explained relatively little of the variance, sleep efficiency, total sleep time and sleep stage transitions were among the most important objective correlates.

  View details for DOI 10.1016/j.biopsycho.2016.11.010

  View details for PubMedID 27889439

  View details for PubMedCentralID PMC5292065

• Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Shadyab, A. H., Macera, C. A., Shaffer, R. A., Jain, S., Gallo, L. C., Gass, M. L., Waring, M. E., Stefanick, M. L., LaCroix, A. Z. 2017; 24 (1): 35-44

  View details for DOI 10.1097/GME.0000000000000710

  View details for Web of Science ID 000391845600007

• Metabolic phenotypes of obesity: frequency, correlates and change over time in a cohort of postmenopausal women INTERNATIONAL JOURNAL OF OBESITY Kabat, G. C., Wu, W., Bea, J. W., Chen, C., Qi, L., Stefanick, M. L., Chlebowski, R. T., Lane, D. S., Wactawski-Wende, J., Wassertheil-Smoller, S., Rohan, T. E. 2017; 41 (1): 170-177

  Abstract

  The possibility that a subset of persons who are obese may be metabolically healthy-referred to as the 'metabolically healthy obese' (MHO) phenotype-has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS).We used repeated measurements available for a subcohort of participants enrolled in the Women's Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5-<25.0, 25.0-<30.0, ⩾30.0 kg m-2) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another.Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of 'regressing' to the metabolically healthy normal-weight phenotype was 52%.The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.

  View details for DOI 10.1038/ijo.2016.179

  View details for Web of Science ID 000394143100023

• No Increase in Fractures After Stopping Hormone Therapy: Results From the Women's Health Initiative JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Watts, N. B., Cauley, J. A., Jackson, R. D., LaCroix, A. Z., Lewis, C. E., Manson, J. E., Neuner, J. M., Phillips, L. S., Stefanick, M. L., Wactawski-Wende, J., Crandall, C. 2017; 102 (1): 302-308

  View details for DOI 10.1210/jc.2016-3270

  View details for Web of Science ID 000397071900035

• Maternal Age at Childbirth and Parity as Predictors of Longevity Among Women in the United States: The Women's Health Initiative. American journal of public health Shadyab, A. H., Gass, M. L., Stefanick, M. L., Waring, M. E., Macera, C. A., Gallo, L. C., Shaffer, R. A., Jain, S., LaCroix, A. Z. 2017; 107 (1): 113-119

  Abstract

  To examine associations of maternal age at childbirth and parity with survival to age 90 years (longevity).We performed a prospective study among a multiethnic cohort of postmenopausal US women in the Women's Health Initiative recruited from 1993 to 1998 and followed through August 29, 2014. We adjusted associations with longevity for demographic, lifestyle, reproductive, and health-related characteristics.Among 20 248 women (mean age at baseline, 74.6 years), 10 909 (54%) survived to age 90 years. The odds of longevity were significantly higher in women with later age at first childbirth (adjusted odds ratio = 1.11; 95% confidence interval = 1.02, 1.21 for age 25 years or older vs younger than 25 years; P for trend = .04). Among parous women, the relationship between parity and longevity was significant among White but not Black women. White women with 2 to 4 term pregnancies compared with 1 term pregnancy had higher odds of longevity.Reproductive events were associated with longevity among women. Future studies are needed to determine whether factors such as socioeconomic status explain associations between reproductive events and longevity.

  View details for PubMedID 27854529

  View details for PubMedCentralID PMC5308150

• No Increase in Fractures After Stopping Hormone Therapy: Results From the Women's Health Initiative. journal of clinical endocrinology and metabolism Watts, N. B., Cauley, J. A., Jackson, R. D., LaCroix, A. Z., Lewis, C. E., Manson, J. E., Neuner, J. M., Phillips, L. S., Stefanick, M. L., Wactawski-Wende, J., Crandall, C. 2017; 102 (1): 302-308

  Abstract

  The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT.The purpose of this study was to examine fractures after discontinuation of HT.Two placebo-controlled randomized trials served as the study setting.Study patients included WHI participants (N = 15,187) who continued active HT or placebo through the intervention period and who did not take HT in the postintervention period.Trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) in naturally menopausal women and CEE alone in women with prior hysterectomy.Total fractures and hip fractures through 5 years after discontinuation of HT were recorded.Hip fractures were infrequent (∼2.5 per 1000 person-years); this finding was similar between trials and in former HT and placebo groups. There was no difference in total fractures in the CEE + MPA trial for former HT vs former placebo users (28.9 per 1000 person-years and 29.9 per 1000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87 to 1.09; P = 0.63); however, in the CEE-alone trial, total fractures were higher in former placebo users (36.9 per 1000 person-years) compared with the former active group (31.1 per 1000 person-years), a finding that was suggestive of a residual benefit of CEE against total fractures (HR, 0.85; 95% CI, 0.73 to 0.98; P = 0.03).We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with former placebo users after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.

  View details for DOI 10.1210/jc.2016-3270

  View details for PubMedID 27820659

• Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative A Randomized Controlled Trial OBSTETRICS AND GYNECOLOGY Schnatz, P. F., Jiang, X., Aragaki, A. K., Nudy, M., O'Sullivan, D. M., Williams, M., LeBlanc, E. S., Martin, L. W., Manson, J. E., Shikany, J. M., Johnson, K. C., Stefanick, M. L., Payne, M. E., Cauley, J. A., Howard, B. V., Robbins, J. 2017; 129 (1): 121-129

  Abstract

  To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors.We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C).Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03).Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision.ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

  View details for DOI 10.1097/AOG.0000000000001774

  View details for Web of Science ID 000391951900016

  View details for PubMedID 27926633

  View details for PubMedCentralID PMC5177479

• Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LeBlanc, E. S., Kapphahn, K., Hedlin, H., Desai, M., Parikh, N. I., Liu, S., Parker, D. R., Anderson, M., Aroda, V., Sullivan, S., Woods, N. F., Waring, M. E., Lewis, C. E., Stefanick, M. 2017; 24 (1): 64-72

  Abstract

  The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk.Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes.In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment.Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

  View details for DOI 10.1097/GME.0000000000000714

  View details for Web of Science ID 000391845600010

  View details for PubMedID 27465714

• Reply to Comment on 'Statin use and all-cancer survival: prospective results from the Women's Health Initiative'. British journal of cancer Wang, A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Chlebowski, R. T., Simon, M., Desai, P., Wassertheil-Smoller, S., Liu, S., Kritchevsky, S., Wakelee, H. A., Stefanick, M. L. 2017; 116 (3)

  View details for DOI 10.1038/bjc.2016.396

  View details for PubMedID 27923034

• Protective Effects of Statins in Cancer: Should They Be Prescribed for High-Risk Patients? Current atherosclerosis reports Wang, A., Wakelee, H. A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Stefanick, M. L. 2016; 18 (12): 72-?

  Abstract

  Statins are one of the most widely prescribed drug classes in the USA. This review aims to summarize recent research on the relationship between statin use and cancer outcomes, in the context of clinical guidelines for statin use in patients with cancer or who are at high risk for cancer.A growing body of research has investigated the relationship between statins and cancer with mixed results. Cancer incidence has been more extensively studied than cancer survival, though results are inconsistent as some large meta-analyses have not found an association, while other studies have reported improved cancer outcomes with the use of statins. Additionally, two large studies reported increased all-cancer survival with statin use. Studies on specific cancer types in relation to cancer use have also been mixed, though the most promising results appear to be found in gastrointestinal cancers. Few studies have reported an increased risk of cancer incidence or decreased survival with statin use, though this type of association has been more commonly reported for cutaneous cancers. The overall literature on statins in relation to cancer incidence and survival is mixed, and additional research is warranted before any changes in clinical guidelines can be recommended. Future research areas include randomized controlled trials, studies on specific cancer types in relation to statin use, studies on populations without clinical indication for statins, elucidation of underlying biological mechanisms, and investigation of different statin types. However, studies seem to suggest that statins may be protective and are not likely to be harmful in the setting of cancer, suggesting that cancer patients who already take statins should not have this medication discontinued.

  View details for PubMedID 27796821

• Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative. International journal of cancer Wang, A., Qin, F., Hedlin, H., Desai, M., Chlebowski, R., Gomez, S., Eaton, C. B., Johnson, K. C., Qi, L., Wactawski-Wende, J., Womack, C., Wakelee, H. A., Stefanick, M. L. 2016; 139 (10): 2178-2192

  Abstract

  Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50-79 years between 1993-1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)-minutes/week: none <100 (reference), low 100-<500, medium 500-<1200, high 1200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow-up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared to no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p=0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76-0.96); medium, HR: 0.82 (0.73-0.93); and high, HR: 0.90 (0.79-1.03)], and mortality [p<0.0001; low, HR: 0.80 (0.69-0.92); medium, HR: 0.68 (0.59-0.80); and high, HR: 0.78 (0.66-0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p=0.01), with a stronger association in women with BMI<30 kg/m(2) . Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non-obese women. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ijc.30281

  View details for PubMedID 27439221

• Neighborhood Walkability and Adiposity in the Women's Health Initiative Cohort. American journal of preventive medicine Sriram, U., LaCroix, A. Z., Barrington, W. E., Corbie-Smith, G., Garcia, L., Going, S. B., LaMonte, M. J., Manson, J. E., Sealy-Jefferson, S., Stefanick, M. L., Waring, M. E., Seguin, R. A. 2016; 51 (5): 722-730

  Abstract

  Neighborhood environments may play a role in the rising prevalence of obesity among older adults. However, research on built environmental correlates of obesity in this age group is limited. The current study aimed to explore associations of Walk Score, a validated measure of neighborhood walkability, with BMI and waist circumference in a large, diverse sample of older women.This study linked cross-sectional data on 6,526 older postmenopausal women from the Women's Health Initiative Long Life Study (2012-2013) to Walk Scores for each participant's address (collected in 2012). Linear and logistic regression models were used to estimate associations of BMI and waist circumference with continuous and categorical Walk Score measures. Secondary analyses examined whether these relationships could be explained by walking expenditure or total physical activity. All analyses were conducted in 2015.Higher Walk Score was not associated with BMI or overall obesity after adjustment for sociodemographic, medical, and lifestyle factors. However, participants in highly walkable areas had significantly lower odds of abdominal obesity (waist circumference >88 cm) as compared with those in less walkable locations. Observed associations between walkability and adiposity were partly explained by walking expenditure.Findings suggest that neighborhood walkability is linked to abdominal adiposity, as measured by waist circumference, among older women and provide support for future longitudinal research on associations between Walk Score and adiposity in this population.

  View details for DOI 10.1016/j.amepre.2016.04.007

  View details for PubMedID 27211897

  View details for PubMedCentralID PMC5067165

• Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS). Journal of bone and mineral research Cauley, J. A., Cawthon, P. M., Peters, K. E., Cummings, S. R., Ensrud, K. E., Bauer, D. C., Taylor, B. C., Shikany, J. M., Hoffman, A. R., Lane, N. E., Kado, D. M., Stefanick, M. L., Orwoll, E. S. 2016; 31 (10): 1810-1819

  Abstract

  Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow-up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person-years (PY) was greatest in men with FNBMD T-scores <-2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age <70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.

  View details for DOI 10.1002/jbmr.2836

  View details for PubMedID 26988112

  View details for PubMedCentralID PMC5240502

• The associations of leptin, adiponectin and resistin with incident atrial fibrillation in women. Heart Ermakov, S., Azarbal, F., Stefanick, M. L., LaMonte, M. J., Li, W., Tharp, K. M., Martin, L. W., Nassir, R., Salmoirago-Blotcher, E., Albert, C. M., Manson, J. E., Assimes, T. L., Hlatky, M. A., Larson, J. C., Perez, M. V. 2016; 102 (17): 1354-1362

  Abstract

  Higher body mass index (BMI) is an important risk factor for atrial fibrillation (AF). The adipokines leptin, adiponectin and resistin are correlates of BMI, but their association with incident AF is not well known. We explored this relationship in a large cohort of postmenopausal women.We studied an ethnically diverse cohort of community-dwelling postmenopausal women aged 50-79 who were nationally recruited at 40 clinical centres as part of the Women's Health Initiative investigation. Participants underwent measurements of baseline serum leptin, adiponectin and resistin levels and were followed for incident AF. Adipokine levels were log transformed and normalised using inverse probability weighting. Cox proportional hazard regression models were used to estimate associations with adjustment for known AF risk factors.Of the 4937 participants included, 892 developed AF over a follow-up of 11.1 years. Those with AF had higher mean leptin (14.9 pg/mL vs 13.9 pg/mL), adiponectin (26.3 ug/mL vs 24.5 ug/mL) and resistin (12.9 ng/mL vs 12.1 ng/mL) levels. After multivariable adjustment, neither log leptin nor log adiponectin levels were significantly associated with incident AF. However, log resistin levels remained significantly associated with incident AF (HR=1.57 per 1 log (ng/mL) increase, p=0.006). Additional adjustment for inflammatory cytokines only partially attenuated the association between resistin and incident AF (HR=1.43, p=0.06 adjusting for C-reactive protein (CRP); HR=1.39, p=0.08 adjusting for IL-6). Adjusting for resistin partially attenuated the association between BMI and incident AF (HR=1.14 per 5 kg/m(2), p=0.006 without resistin; HR=1.12, p=0.02 with resistin).In women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.

  View details for DOI 10.1136/heartjnl-2015-308927

  View details for PubMedID 27146694

• Pet Ownership and Cancer Risk in the Women's Health Initiative. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Garcia, D. O., Lander, E. M., Wertheim, B. C., Manson, J. E., Volpe, S. L., Chlebowski, R. T., Stefanick, M. L., Lessin, L. S., Kuller, L. H., Thomson, C. A. 2016; 25 (9): 1311-1316

  Abstract

  Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers.This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders.There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons.Pet ownership had no association with overall cancer incidence.This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. ©2016 AACR.

  View details for DOI 10.1158/1055-9965.EPI-16-0218

  View details for PubMedID 27365150

  View details for PubMedCentralID PMC5010503

• Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women's Health Initiative: A Longitudinal Study from the United States PLOS MEDICINE Arnold, M., Jiang, L., Stefanick, M. L., Johnson, K. C., Lane, D. S., LeBlanc, E. S., Prentice, R., Rohan, T. E., Snively, B. M., Vitolins, M., Zaslavsky, O., Soerjomataram, I., Anton-Culver, H. 2016; 13 (8)

  Abstract

  High body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women.Participants from the observational study of the Women's Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06-1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much more pronounced in women who never used postmenopausal hormones. This study has limitations because some of the anthropometric information was obtained from retrospective self-reports. Furthermore, data from longitudinal studies with long-term follow-up and repeated anthropometric measures are typically subject to missing data at various time points, which was also the case in this study. Yet, this limitation was partially overcome by using growth curve models, which enabled us to impute data at missing time points for each participant.In summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.

  View details for DOI 10.1371/journal.pmed.1002081

  View details for Web of Science ID 000383357400010

  View details for PubMedID 27529652

  View details for PubMedCentralID PMC4987008

• Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative. Menopause (New York, N.Y.) Shadyab, A. H., Macera, C. A., Shaffer, R. A., Jain, S., Gallo, L. C., Gass, M. L., Waring, M. E., Stefanick, M. L., LaCroix, A. Z. 2016: -?

  Abstract

  The aim of the present study was to investigate associations between reproductive factors and survival to age 90 years.This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics.Participants were on average aged 74.7 years (range, 69-81 y) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% CI, 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend = 0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50 to 54 and at least 55 compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend = 0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend = 0.008). The odds of longevity were 13% (OR 1.13; 95% CI, 1.03-1.25) higher in women with more than 40 compared with less than 33 reproductive years.Reproductive characteristics were associated with late-age survival in older women.

  View details for PubMedID 27465713

  View details for PubMedCentralID PMC5177476

• Associations of total and free 25OHD and 1,25(OH)(2)D with serum markers of inflammation in older men OSTEOPOROSIS INTERNATIONAL Srikanth, P., Chun, R. F., Hewison, M., Adams, J. S., Bouillon, R., Vanderschueren, D., Lane, N., Cawthon, P. M., Dam, T., Barrett-Connor, E., Daniels, L. B., Shikany, J. M., Stefanick, M. L., Cauley, J. A., Orwoll, E. S., Nielson, C. M. 2016; 27 (7): 2291-2300

  Abstract

  Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.IL-6 was lower in men with higher 25OHD (-0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 μg/mL) and with higher 1,25(OH)2D (-0.20 μg/mL, 95 % CI -0.0004 to -0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D).Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

  View details for DOI 10.1007/s00198-016-3537-3

  View details for Web of Science ID 000378004800015

  View details for PubMedID 26905270

  View details for PubMedCentralID PMC4902735

• Sex differences in obesity, dietary habits, and physical activity among urban middle-class Bangladeshis. International journal of health sciences Saquib, J., Saquib, N., Stefanick, M. L., Khanam, M. A., Anand, S., Rahman, M., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2016; 10 (3): 363-372

  Abstract

  The sustained economic growth in Bangladesh during the previous decade has created a substantial middle-class population, who have adequate income to spend on food, clothing, and lifestyle management. Along with the improvements in living standards, has also come negative impact on health for the middle class. The study objective was to assess sex differences in obesity prevalence, diet, and physical activity among urban middle-class Bangladeshi.In this cross-sectional study, conducted in 2012, we randomly selected 402 adults from Mohammedpur, Dhaka. The sampling technique was multi-stage random sampling. We used standardized questionnaires for data collection and measured height, weight, and waist circumference.Mean age (standard deviation) was 49.4 (12.7) years. The prevalence of both generalized (79% vs. 53%) and central obesity (85% vs. 42%) were significantly higher in women than men. Women reported spending more time watching TV and spending less time walking than men (p<.05); however, men reported a higher intake of unhealthy foods such as fast food and soft drinks.We conclude that the prevalence of obesity is significantly higher in urban middle-class Bangladeshis than previous urban estimates, and the burden of obesity disproportionately affects women. Future research and public health efforts are needed to address this severe obesity problem and to promote active lifestyles.

  View details for PubMedID 27610059

  View details for PubMedCentralID PMC5003579

• Association of Leptin with Body Pain in Women. Journal of women's health (2002) Younger, J., Kapphahn, K., Brennan, K., Sullivan, S. D., Stefanick, M. L. 2016; 25 (7): 752-760

  Abstract

  Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

  View details for DOI 10.1089/jwh.2015.5509

  View details for PubMedID 27028709

  View details for PubMedCentralID PMC4939369

• Parity and Oral Contraceptive Use in Relation to Ovarian Cancer Risk in Older Women CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION McGuire, V., Hartge, P., Liao, L. M., Sinha, R., Bernstein, L., Canchola, A. J., Anderson, G. L., Stefanick, M. L., Whittemore, A. S. 2016; 25 (7): 1059-1063

  Abstract

  Several studies have suggested that the ovarian cancer risk reductions associated with parity and oral contraceptive use are weaker in postmenopausal than premenopausal women, yet little is known about the persistence of these reductions as women age. This question gains importance with the increasing numbers of older women in the population.We addressed the question using data from three large U.S. cohort studies involving 310,290 white women aged 50+ years at recruitment, of whom 1,815 developed subsequent incident invasive epithelial ovarian cancer. We used Cox regression, stratified by cohort, to examine age-related trends in the HRs per full-term pregnancy and per year of oral contraceptive use.The parity-associated risk reductions waned with age (Ptrend < 0.001 in HR with increasing age), particularly among women aged 75 years or more, for whom we observed no association with parity. However, we observed no such attenuation in the oral contraceptive-associated risk reductions (P = 0.79 for trend in HR with increasing age).These findings suggest that prior oral contraceptive use is important for ovarian cancer risk assessment among women of all ages, while the benefits of parity wane as women age.This information, if duplicated in other studies, will be useful to preventive counseling and risk prediction, particularly for women at increased ovarian cancer risk due to a personal history of breast cancer or a family history of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1059-63. ©2016 AACR.

  View details for DOI 10.1158/1055-9965.EPI-16-0011

  View details for Web of Science ID 000380072700007

  View details for PubMedID 27197274

  View details for PubMedCentralID PMC4930714

• Statin use and all-cancer survival: prospective results from the Women's Health Initiative BRITISH JOURNAL OF CANCER Wang, A., Aragaki, A. K., Tang, J. Y., Kurian, A. W., Manson, J. E., Chlebowski, R. T., Simon, M., Desai, P., Wassertheil-Smoller, S., Liu, S., Kritchevsky, S., Wakelee, H. A., Stefanick, M. L. 2016; 115 (1): 129-135

  Abstract

  This study aims to investigate the association between statin use and all-cancer survival in a prospective cohort of postmenopausal women, using data from the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT).The WHI study enrolled women aged 50-79 years from 1993 to 1998 at 40 US clinical centres. Among 146 326 participants with median 14.6 follow-up years, 23 067 incident cancers and 3152 cancer deaths were observed. Multivariable-adjusted Cox proportional hazards models were used to investigate the relationship between statin use and cancer survival.Compared with never-users, current statin use was associated with significantly lower risk of cancer death (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.71-0.86, P<0.001) and all-cause mortality (HR, 0.80; 95% CI, 0.74-0.88). Use of other lipid-lowering medications was also associated with increased cancer survival (P-interaction (int)=0.57). The lower risk of cancer death was not dependent on statin potency (P-int=0.22), lipophilicity/hydrophilicity (P-int=0.43), type (P-int=0.34) or duration (P-int=0.33). However, past statin users were not at lower risk of cancer death compared with never-users (HR, 1.06; 95% CI, 0.85-1.33); in addition, statin use was not associated with a reduction of overall cancer incidence despite its effect on survival (HR, 0.96; 95% CI, 0.92-1.001).In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications was associated with decreased cancer death, regardless of the type, duration, or potency of statin medications used.British Journal of Cancer advance online publication, 9 June 2016; doi:10.1038/bjc.2016.149 www.bjcancer.com.

  View details for DOI 10.1038/bjc.2016.149

  View details for Web of Science ID 000378880400020

  View details for PubMedID 27280630

• Racial and ethnic differences in atrial fibrillation risk factors and predictors in women: Findings from the Women's Health Initiative AMERICAN HEART JOURNAL Rodriguez, F., Stefanick, M. L., Greenland, P., Soliman, E. Z., Manson, J. E., Parikh, N., Martin, L. W., Larson, J. C., Hlatky, M., Nassir, R., Cene, C. W., Rodriguez, B. L., Albert, C., Perez, M. V. 2016; 176: 70-77

  Abstract

  The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women.We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims.Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups.In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians.

  View details for DOI 10.1016/j.ahj.2016.03.004

  View details for Web of Science ID 000377472000013

  View details for PubMedID 27264222

• Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian, postmenopausal women in the Women's Health Initiative CANCER CAUSES & CONTROL Ransohoff, K. J., Ally, M. S., Stefanick, M. L., Keiser, E., Spaunhurst, K., Kapphahn, K., Pagoto, S., Messina, C., Hedlin, H., Manson, J. E., Tang, J. Y. 2016; 27 (6): 817-823

  Abstract

  Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.Women were followed with yearly surveys throughout the duration of their participation in the Women's Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

  View details for DOI 10.1007/s10552-016-0730-9

  View details for Web of Science ID 000376619500011

  View details for PubMedID 27153844

• Lean body mass and risk of incident atrial fibrillation in post-menopausal women EUROPEAN HEART JOURNAL Azarbal, F., Stefanick, M. L., Assimes, T. L., Manson, J. E., Bea, J. W., Li, W., Hlatky, M. A., Larson, J. C., LeBlanc, E. S., Albert, C. M., Nassir, R., Martin, L. W., Perez, M. V. 2016; 37 (20): 1606-1613

  Abstract

  High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF.The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31).Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.

  View details for DOI 10.1093/eurheartj/ehv423

  View details for Web of Science ID 000376168100013

  View details for PubMedID 26371115

• Individual and Neighborhood Socioeconomic Status and the Association between Air Pollution and Cardiovascular Disease. Environmental health perspectives Chi, G. C., Hajat, A., Bird, C. E., Cullen, M. R., Griffin, B. A., Miller, K. A., Shih, R. A., Stefanick, M. L., Vedal, S., Whitsel, E. A., Kaufman, J. D. 2016: -?

  Abstract

  Long-term fine particulate matter (PM2.5) exposure is linked with cardiovascular disease, and disadvantaged status may increase susceptibility to air pollution-related health effects. In addition, there are concerns that this association may be partially explained by confounding by socioeconomic status (SES).We examined the roles that individual- and neighborhood-level SES (NSES) play in the association between PM2.5 exposure and cardiovascular disease.The study population comprised 51,754 postmenopausal women from the Women's Health Initiative Observational Study. PM2.5 concentrations were predicted at participant residences using fine-scale regionalized universal kriging models. We assessed individual-level SES and NSES (Census-tract level) across several SES domains including education, occupation, and income/wealth, as well as through an NSES score, which captures several important dimensions of SES. Cox proportional-hazards regression adjusted for SES factors and other covariates to determine the risk of a first cardiovascular event.A 5 μg/m3 higher exposure to PM2.5 was associated with a 13% increased risk of cardiovascular event [hazard ratio (HR) 1.13; 95% confidence interval (CI): 1.02, 1.26]. Adjustment for SES factors did not meaningfully affect the risk estimate. Higher risk estimates were observed among participants living in low-SES neighborhoods. The most and least disadvantaged quartiles of the NSES score had HRs of 1.39 (95% CI: 1.21, 1.61) and 0.90 (95% CI: 0.72, 1.07), respectively.Women with lower NSES may be more susceptible to air pollution-related health effects. The association between air pollution and cardiovascular disease was not explained by confounding from individual-level SES or NSES. Citation: Chi GC, Hajat A, Bird CE, Cullen MR, Griffin BA, Miller KA, Shih RA, Stefanick ML, Vedal S, Whitsel EA, Kaufman JD. 2016. Individual and neighborhood socioeconomic status and the association between air pollution and cardiovascular disease. Environ Health Perspect 124:1840-1847; http://dx.doi.org/10.1289/EHP199.

  View details for PubMedID 27138533

  View details for PubMedCentralID PMC5132637

• Medication use trajectories of postmenopausal breast cancer survivors and matched cancer-free controls BREAST CANCER RESEARCH AND TREATMENT Pan, K., Chlebowski, R. T., Simon, M. S., Ray, R. M., Livaudais-Toman, J., Sullivan, S. D., Stefanick, M. L., Wallace, R. B., Leboff, M., Bluhm, E. C., Paskett, E. D. 2016; 156 (3): 567-576

  Abstract

  While adverse medical sequelae are associated with breast cancer therapies, information on breast cancer impact on medication use is limited. Therefore, we compared medication use before and after diagnosis of early stage breast cancer to medication use in matched, cancer-free controls. Of 68,132 Women's Health Initiative participants, 3726 were diagnosed with breast cancer and, after exclusions, in 1731 breast cancer cases, medication use before and >3 years after diagnosis (mean 5.3 ± 2.1 SD) was compared to use in 1731 cancer-free matched controls on similar inventory dates. The medication category number at follow-up inventory was the primary study outcome. Medication category use (n, mean, SD) was comparable at baseline and significantly increased at follow-up in both cases (2.48 ± 1.66 vs. 4.15 ± 2.13, baseline vs follow-up, respectively, P < .0001) and controls (2.44 ± 1.67 vs. 3.95 ± 2.13, respectively, P < .0001), with clinically marginal but statistically significant additional medication category use by cases (0.20 ± 2.40, P < .0001). Tamoxifen users used somewhat more selected medication categories at follow-up assessment (mean 3.40 ± 1.89 vs. 3.21 ± 1.99, respectively, P = 0.05), while aromatase inhibitor users used more medication categories (mean 4.85 ± 2.10 vs. 4.44 ± 1.94, respectively, P = 0.02). No increase in medication category was seen in cases who were not current endocrine therapy users. Breast cancer survivors having only a clinically marginal increase in medication use compared to cancer-free controls. These findings highlight the importance of incorporation of control populations in studies of cancer survivorship.

  View details for DOI 10.1007/s10549-016-3773-4

  View details for Web of Science ID 000374666500018

  View details for PubMedID 27075917

• Sleep Disordered Breathing and Risk of Stroke in Older Community-Dwelling Men SLEEP Stone, K. L., Blackwell, T. L., Ancoli-Israel, S., Barrett-Connor, E., Bauer, D. C., Cauley, J. A., Ensrud, K. E., Hoffman, A. R., Mehra, R., Stefanick, M. L., Varosy, P. D., Yaffe, K., Redline, S. 2016; 39 (3): 531-540

  Abstract

  Men with sleep disordered breathing (SDB) may be at increased stroke risk, due to nocturnal hypoxemia, sleep loss or fragmentation, or other mechanisms. We examined the association of SDB with risk of incident stroke in a large cohort of older men.Participants were 2,872 community-dwelling men (mean age 76 years) enrolled in the MrOS Sleep Study, which gathered data from 2003 to 2005 at six clinical sites in the Unites States. SDB predictors (obstructive apnea-hypopnea index, apnea-hypopnea index, central apnea index, and nocturnal hypoxemia) were measured using overnight polysomnography. Incident stroke over an average follow-up of 7.3 years was centrally adjudicated by physician review of medical records.One hundred fifty-six men (5.4%) had a stroke during follow-up. After adjustment for age, clinic site, race, body mass index, and smoking status, older men with severe nocturnal hypoxemia (≥ 10% of the night with SpO2 levels below 90%) had a 1.8-fold increased risk of incident stroke compared to those without nocturnal hypoxemia (relative hazard = 1.83; 95% confidence interval 1.12-2.98; P trend = 0.02). Results were similar after further adjustment for other potential covariates and after excluding men with a history of stroke. Other indices of SDB were not associated with incident stroke.Older men with severe nocturnal hypoxemia are at significantly increased risk of incident stroke. Measures of overnight oxygen saturation may better identify older men at risk for stroke than measures of apnea frequency.

  View details for DOI 10.5665/sleep.5520

  View details for Web of Science ID 000371115800007

  View details for PubMedID 26943468

  View details for PubMedCentralID PMC4763364

• The Relationship of Cardiovascular Disease to Physical Functioning in Women Surviving to Age 80 and Above in the Women's Health Initiative. journals of gerontology. Series A, Biological sciences and medical sciences Stefanick, M. L., Brunner, R. L., Leng, X., Limacher, M. C., Bird, C. E., Garcia, D. O., Hogan, P. E., LaMonte, M. J., Mackey, R. H., Johnson, K. C., LaCroix, A., Robinson, J. G., Seguin, R. A., Tindle, H. A., Wassertheil-Smoller, S. 2016; 71: S42-53

  Abstract

  Cardiovascular disease (CVD) is highly prevalent at ages 80 and above. The association of physical functioning (PF), a key to an optimal aging trajectory, with CVD and specific CVD diagnosis in women who survive to age 80 and above has not been described previously and has important public health significance given our aging population.Women's Health Initiative participants aged 80 years or older at the time of self-reporting PF (RAND SF-36) were studied in relationship to CVD diagnosis, whether present at study baseline (1993-1998) or diagnosed during follow-up through 2012. Cross-sectional analyses utilized demographic, medical, lifestyle, and psycho-social questionnaire data from baseline or updated at the time of self-reported PF.Among 27,145 older Women's Health Initiative participants, 22.0% (N = 5,959) had been diagnosed with CVD, specifically: 11.3% (N = 3,071) with coronary heart disease; 4.7% (N = 1,279), stroke; 5.2% (N = 1,397), venous thromboembolism; 2.7% (N = 737), peripheral arterial disease; and 2.7% (N = 725), congestive heart failure. PF scores (mean ± SE) were significantly (p < .0001) higher without CVD (60.0±26.9), compared with any CVD (47.9±27.3), and for each specific CVD diagnosis: coronary heart disease (48.8±27.1); stroke (44.8±27.9); venous thromboembolism (48.9±27.4); peripheral arterial disease (41.9±2.2); and congestive heart failure (38.8±26.1). Regardless of CVD diagnosis, higher PF was associated with: younger age at the time of PF assessment; lower body mass index; higher recreational physical activity; better self-reported general health; fewer hip fractures after age 55; no history of arthritis; and no recent use of non-steroidal anti-inflammatory drugs.Older women with any CVD, and particularly women with congestive heart failure or peripheral arterial disease, reported significantly lower PF compared to women with no CVD. Regardless of CVD diagnosis, higher PF was strongly associated with a more active lifestyle and lower body mass index, suggesting potential intervention targets for more optimal aging.

  View details for DOI 10.1093/gerona/glv087

  View details for PubMedID 26858324

• Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative. British journal of cancer Wang, A., Stefanick, M. L., Kapphahn, K., Hedlin, H., Desai, M., Manson, J. A., Strickler, H., Martin, L., Wactawski-Wende, J., Simon, M., Tang, J. Y. 2016; 114 (3): 314-320

  Abstract

  The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women's Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women.The WHI study enrolled women aged 50-79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models.Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (ORadj) 1.21; 95% confidence interval (CI): 1.07-1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08-2.16), simvastatin (OR 1.38; 95% CI: 1.12-1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18-1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin-NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history.Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration-effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship.

  View details for DOI 10.1038/bjc.2015.376

  View details for PubMedID 26742009

  View details for PubMedCentralID PMC4742576

• Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative AMERICAN JOURNAL OF KIDNEY DISEASES Arce, C. M., Rhee, J. J., Cheung, K. L., Hedlin, H., Kapphahn, K., Franceschini, N., Kalil, R. S., Martin, L. W., Qi, L., Shara, N. M., Desai, M., Stefanick, M. L., Winkelmayer, W. C. 2016; 67 (2): 198-208

  Abstract

  Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative.Prospective cohort study.Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs).Categories of eGFR (exposure); race/ethnicity (effect modifier).The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories.Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

  View details for DOI 10.1053/j.ajkd.2015.07.020

  View details for Web of Science ID 000368418800011

  View details for PubMedCentralID PMC4724531

• Sleep Disturbance, Diabetes, and Cardiovascular Disease in Postmenopausal Veteran Women GERONTOLOGIST Rissling, M. B., Gray, K. E., Ulmer, C. S., Martin, J. L., Zaslavsky, O., Gray, S. L., Hale, L., Zeitzer, J. M., Naughton, M., Woods, N. F., LaCroix, A., Calhoun, P. S., Stefanick, M., Weitlauf, J. C. 2016; 56: S54-S66

  Abstract

  To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI).The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans.Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans.Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.

  View details for DOI 10.1093/geront/gnv668

  View details for Web of Science ID 000374221500007

  View details for PubMedID 26768391

• Military Generation and Its Relationship to Mortality in Women Veterans in the Women's Health Initiative GERONTOLOGIST Washington, D. L., Bird, C. E., LaMonte, M. J., Goldstein, K. M., Rillamas-Sun, E., Stefanick, M. L., Woods, N. F., Bastian, L. A., Gass, M., Weitlauf, J. C. 2016; 56: S126-S137

  Abstract

  Women's military roles, exposures, and associated health outcomes have changed over time. However, mortality risk-within military generations or compared with non-Veteran women-has not been assessed. Using data from the Women's Health Initiative (WHI), we examined all-cause and cause-specific mortality by Veteran status and military generation among older women.WHI participants (3,719 Veterans; 141,802 non-Veterans), followed for a mean of 15.2 years, were categorized into pre-Vietnam or Vietnam/after generations based on their birth cohort. We used cox proportional hazards models to examine the association between Veteran status and mortality by generation.After adjusting for sociodemographic characteristics and WHI study arm, all-cause mortality hazard rate ratios (HRs) for Veterans relative to non-Veterans were 1.16 (95% CI: 1.09-1.23) for pre-Vietnam and 1.16 (95% CI: 0.99-1.36) for Vietnam/after generations. With additional adjustment for health behaviors and risk factors, this excess mortality rate persisted for pre-Vietnam but attenuated for Vietnam/after generations. After further adjustment for medical morbidities, across both generations, Veterans and non-Veterans had similar all-cause mortality rates. Relative to non-Veterans, adjusting for sociodemographics and WHI study arm, pre-Vietnam generation Veterans had higher cancer, cardiovascular, and trauma-related morality rates; Vietnam/after generation Veterans had the highest trauma-related mortality rates (HR = 2.93, 1.64-5.23).Veterans' higher all-cause mortality rates were limited to the pre-Vietnam generation, consistent with diminution of the healthy soldier effect over the life course. Mechanisms underlying Vietnam/after generation Veteran trauma-related mortality should be elucidated. Efforts to modify salient health risk behaviors specific to each military generation are needed.

  View details for DOI 10.1093/geront/gnv669

  View details for Web of Science ID 000374221500013

  View details for PubMedID 26768386

• Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans. EBioMedicine David, S. P., Wang, A., Kapphahn, K., Hedlin, H., Desai, M., Henderson, M., Yang, L., Walsh, K. M., Schwartz, A. G., Wiencke, J. K., Spitz, M. R., Wenzlaff, A. S., Wrensch, M. R., Eaton, C. B., Furberg, H., Mark Brown, W., Goldstein, B. A., Assimes, T., Tang, H., Kooperberg, C. L., Quesenberry, C. P., Tindle, H., Patel, M. I., Amos, C. I., Bergen, A. W., Swan, G. E., Stefanick, M. L. 2016; 4: 153-161

  Abstract

  Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(- 5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

  View details for DOI 10.1016/j.ebiom.2016.01.002

  View details for PubMedID 26981579

  View details for PubMedCentralID PMC4776066

• Mortality in Postmenopausal Women by Sexual Orientation and Veteran Status GERONTOLOGIST Lehavot, K., Rillamas-Sun, E., Weitlauf, J., Kimerling, R., Wallace, R. B., Sadler, A. G., Woods, N. F., Shipherd, J. C., Mattocks, K., Cirillo, D. J., Stefanick, M. L., Simpson, T. L. 2016; 56: S150-S162

  Abstract

  To examine differences in all-cause and cause-specific mortality by sexual orientation and Veteran status among older women.Data were from the Women's Health Initiative, with demographic characteristics, psychosocial factors, and health behaviors assessed at baseline (1993-1998) and mortality status from all available data sources through 2014. Women with baseline information on lifetime sexual behavior and Veteran status were included in the analyses (N = 137,639; 1.4% sexual minority, 2.5% Veteran). The four comparison groups included sexual minority Veterans, sexual minority non-Veterans, heterosexual Veterans, and heterosexual non-Veterans. Cox proportional hazard models were used to estimate mortality risk adjusted for demographic, psychosocial, and health variables.Sexual minority women had greater all-cause mortality risk than heterosexual women regardless of Veteran status (hazard ratio [HR] = 1.20, 95% confidence interval [CI]: 1.07-1.36) and women Veterans had greater all-cause mortality risk than non-Veterans regardless of sexual orientation (HR = 1.14, 95% CI: 1.06-1.22), but the interaction between sexual orientation and Veteran status was not significant. Sexual minority women were also at greater risk than heterosexual women for cancer-specific mortality, with effects stronger among Veterans compared to non-Veterans (sexual minority × Veteran HR = 1.70, 95% CI: 1.01-2.85).Postmenopausal sexual minority women in the United States, regardless of Veteran status, may be at higher risk for earlier death compared to heterosexuals. Sexual minority women Veterans may have higher risk of cancer-specific mortality compared to their heterosexual counterparts. Examining social determinants of longevity may be an important step to understanding and reducing these disparities.

  View details for DOI 10.1093/geront/gnv125

  View details for Web of Science ID 000374221500015

  View details for PubMedID 26768389

• Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study. Gerontologist Padula, C. B., Weitlauf, J. C., Rosen, A. C., Reiber, G., Cochrane, B. B., Naughton, M. J., Li, W., Rissling, M., Yaffe, K., Hunt, J. R., Stefanick, M. L., Goldstein, M. K., Espeland, M. A. 2016; 56 (1): 115-125

  Abstract

  A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI).We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods.Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke).Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.

  View details for DOI 10.1093/geront/gnv663

  View details for PubMedID 26615021

• Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women's Health Initiative. Journal of clinical oncology Patel, M. I., Wang, A., Kapphahn, K., Desai, M., Chlebowski, R. T., Simon, M. S., Bird, C. E., Corbie-Smith, G., Gomez, S. L., Adams-Campbell, L. L., Cote, M. L., Stefanick, M. L., Wakelee, H. A. 2016; 34 (4): 360-368

  Abstract

  This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women's Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers.Lung cancer diagnoses were centrally adjudicated by pathology review. Baseline survey questionnaires collected sociodemographic and health information. Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age, education, calcium/vitamin D, body mass index, smoking (status, age at start, duration, and pack-years), alcohol, family history, oral contraceptive, hormones, physical activity, and diet.The cohort included 129,951 women--108,487 (83%) non-Hispanic white (NHW); 10,892 (8%) non-Hispanic black (NHB); 4,882 (4%) Hispanic; 3,696 (3%) Asian/Pacific Islander (API); 534 (< 1%) American Indian/Alaskan Native; and 1,994 (1%) other. In unadjusted models, Hispanics had 66% lower odds of lung cancer compared with NHW (odds ratio [OR], 0.34; 95% CI, 0.2 to 0.5), followed by API (OR, 0.45; 95% CI, 0.27 to 0.75) and NHB (OR, 0.75; 95% CI, 0.59 to 0.95). In fully adjusted multivariable models, the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null (OR, 0.59; 95% CI, 0.35 to 0.99). In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women (OR, 0.30 [95% CI, 0.15 to 0.62] and 0.34 [95% CI, 0.16 to 0.75, respectively); however, no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models.Differences in lung cancer incidence and mortality are associated with sociodemographic, clinical, and behavioral factors. These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women. Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality.

  View details for DOI 10.1200/JCO.2015.63.5789

  View details for PubMedID 26700122

  View details for PubMedCentralID PMC4872034

• Association Between Anthropometric Measures and Long-Term Survival in Frail Older Women: Observations from the Women's Health Initiative Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Zaslavsky, O., Rillamas-Sun, E., LaCroix, A. Z., Woods, N. F., Tinker, L. F., Zisberg, A., Shadmi, E., Cochrane, B., Edward, B. J., Kritchevsky, S., Stefanick, M. L., Vitolins, M. Z., Wactawski-Wende, J., Zelber-Sagi, S. 2016; 64 (2): 277-284

  Abstract

  To evaluate the association between currently recommended guidelines and commonly used clinical criteria for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and all-cause mortality in frail older women.Longitudinal prospective cohort study.Women's Health Initiative (WHI)-Observational Study.A sample of women aged 65-84 with complete data to characterize frailty in the third year of WHI follow-up (N = 11,070).Frailty phenotype was determined using the modified Fried criteria. Information on anthropometric measures (BMI, WC, WHR) was collected in clinical examinations. Cox proportional hazards models were used to estimate the effect of BMI, WC, and WHR on mortality adjusted for demographic characteristics and health behaviors.Over a mean follow-up of 11.5 years, there were 2,911 (26%) deaths in the sample. Women with a BMI from 25.0 to 29.9 kg/m(2) (hazard rate ratio (HR) = 0.80, 95% confidence interval (CI) = 0.73-0.88) and those with a BMI from 30.0 to 34.9 kg/m(2) (HR = 0.79, 95% CI = 0.71-0.88) had lower mortality than those with a BMI from 18.5 to 24.9 kg/m(2) . Women with a WHR greater than 0.8 had higher mortality (HR = 1.16, 95% CI = 1.07-1.26) than those with a WHR of 0.8 or less. No difference in mortality was observed according to WC. Stratifying according to chronic morbidity or smoking status or excluding women with early death and unintentional weight loss did not substantially change these findings.In frail, older women, having a BMI between 25.0 and 34.9 kg/m(2) or a WHR of 0.8 or less was associated with lower mortality. Currently recommended healthy BMI guidelines should be reevaluated for frail older women.

  View details for DOI 10.1111/jgs.13930

  View details for Web of Science ID 000371159000004

  View details for PubMedID 26889837

• Sleep duration, cognitive decline, and dementia risk in older women. Alzheimer's & dementia : the journal of the Alzheimer's Association Chen, J., Espeland, M. A., Brunner, R. L., Lovato, L. C., Wallace, R. B., Leng, X., Phillips, L. S., Robinson, J. G., Kotchen, J. M., Johnson, K. C., Manson, J. E., Stefanick, M. L., Sarto, G. E., Mysiw, W. J. 2016; 12 (1): 21-33

  Abstract

  Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking.We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics.We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline.In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

  View details for DOI 10.1016/j.jalz.2015.03.004

  View details for PubMedID 26086180

• Coffee and caffeine consumption and the risk of hypertension in postmenopausal women AMERICAN JOURNAL OF CLINICAL NUTRITION Rhee, J. J., Qin, F., Hedlin, H. K., Chang, T. I., Bird, C. E., Zaslavsky, O., Manson, J. E., Stefanick, M. L., Winkelmayer, W. C. 2016; 103 (1): 210-217

  Abstract

  The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial.We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Women's Health Initiative Observational Study.In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2-3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension.During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all).In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women.

  View details for DOI 10.3945/ajcn.115.120147

  View details for Web of Science ID 000367869500025

  View details for PubMedCentralID PMC4691674

• Sex differences in disease presentation, treatment and clinical outcomes of patients with hepatocellular carcinoma: a single-centre cohort study. BMJ open gastroenterology Ladenheim, M. R., Kim, N. G., Nguyen, P., Le, A., Stefanick, M. L., Garcia, G., Nguyen, M. H. 2016; 3 (1)

  Abstract

  Although sex differences in hepatocellular carcinoma (HCC) risk are well known, it is unclear whether sex differences also exist in clinical presentation and survival outcomes once HCC develops.We performed a retrospective cohort study of 1886 HCC patients seen in a US medical centre in 1998-2015. Data were obtained by chart review with survival data also by National Death Index search.The cohort consisted of 1449 male and 437 female patients. At diagnosis, men were significantly younger than women (59.9±10.7 vs 64.0±11.6, p<0.0001). Men had significantly higher rates of tobacco (57.7% vs 31.0%, p<0.001) and alcohol use (63.2% vs 35.1%, p<0.001). Women were more likely to be diagnosed by routine screening versus symptomatically or incidentally (65.5% vs 58.2%, p=0.03) and less likely to present with tumours >5 cm (30.2% vs 39.8%, p=0.001). Surgical and non-surgical treatment utilisation was similar for both sexes. Men and women had no significant difference in median survival from the time of diagnosis (median 30.7 (range=24.5-41.3) vs 33.1 (range=27.4-37.3) months, p=0.84). On multivariate analysis, significant predictors for improved survival included younger age, surgical or non-surgical treatment (vs supportive care), diagnosis by screening, tumour within Milan criteria and lower Model for End-Stage Liver Disease score, but not female sex (adjusted HR=1.01, CI 0.82 to 1.24, p=0.94).Although men have much higher risk for HCC development, there were no significant sex differences in disease presentation or survival except for older age and lower tumour burden at diagnosis in women. Female sex was not an independent predictor for survival.

  View details for DOI 10.1136/bmjgast-2016-000107

  View details for PubMedID 27493763

  View details for PubMedCentralID PMC4964155

• A pilot study combining Go4Life® materials with an interactive voice response system to promote physical activity in older women. Journal of women & aging Saquib, J., King, A. C., Castro, C. M., Tinker, L. F., Sims, S., Shikany, J. M., Bea, J. W., LaCroix, A. Z., Van Horn, L., Stefanick, M. L. 2016; 28 (5): 454-462

  Abstract

  Telephone-based interactive voice response (IVR) systems could be an effective tool for promotion of physical activity among older women. To test IVR feasibility, we enrolled 30 older women in a 10-week physical activity intervention designed around National Institute on Aging (NIA) Go4Life® educational materials with IVR coaching. Participants (mean age = 76 years) significantly increased physical activity by a mean 79 ± 116 (SD) minutes/week (p < .001). Participants reported that the Go4Life® materials, pedometer, and IVR coaching (70% reported easy technology) were useful tools for change. This pilot study demonstrates IVR acceptability as an evidence-based physical activity program for older women.

  View details for DOI 10.1080/08952841.2015.1018065

  View details for PubMedID 27387264

• Pre-diagnostic Sleep Duration and Sleep Quality in Relation to Subsequent Cancer Survival JOURNAL OF CLINICAL SLEEP MEDICINE Phipps, A. I., Bhatti, P., Neuhouser, M. L., Chen, C., Crane, T. E., Kroenke, C. H., Ochs-Balcom, H., Rissling, M., Snively, B. M., Stefanick, M. L., Treggiari, M. M., Watson, N. F. 2016; 12 (4): 495-503

  Abstract

  Poor sleep quality and short sleep duration have been associated with elevated risk for several cancer types; however, the relationship between sleep and cancer outcomes has not been well characterized. We assessed the association between pre-diagnostic sleep attributes and subsequent cancer survival within the Women's Health Initiative (WHI).We identified WHI participants in whom a first primary invasive cancer had been diagnosed during follow-up (n = 21,230). Participants provided information on sleep characteristics at enrollment. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between these pre-diagnostic sleep characteristics and cancer-specific survival for all cancers combined and separately for common cancers. Analyses were adjusted for age, study arm, cancer site, marital status, income, smoking, physical activity, and time to diagnosis.No individual pre-diagnostic sleep characteristics were found to be significantly associated with cancer survival in analyses of all cancer sites combined; however, women who reported short sleep duration (≤ 6 h sleep/night) combined with frequent snoring (≥ 5 nights/w experienced significantly poorer cancer-specific survival than those who reported 7-8 h of sleep/night and no snoring (HR = 1.32, 95% CI: 1.14-1.54). Short sleep duration (HR = 1.46, 95% CI: 1.07-1.99) and frequent snoring (HR = 1.34, 95% CI: 0.98-1.85) were each associated with poorer breast cancer survival; those reporting short sleep combined with frequent snoring combined had substantially poorer breast cancer survival than those reporting neither (HR = 2.14, 95% CI: 1.47-3.13).Short sleep duration combined with frequent snoring reported prior to cancer diagnosis may influence subsequent cancer survival, particularly breast cancer survival.

  View details for DOI 10.5664/jcsm.5674

  View details for Web of Science ID 000374140000006

  View details for PubMedID 26612513

  View details for PubMedCentralID PMC4795275

• Evaluation of the Usefulness of Consensus Definitions of Sarcopenia in Older Men: Results from the Observational Osteoporotic Fractures in Men Cohort Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Cawthon, P. M., Blackwell, T. L., Cauley, J., Kado, D. M., Barrett-Connor, E., Lee, C. G., Hoffman, A. R., Nevitt, M., Stefanick, M. L., Lane, N. E., Ensrud, K. E., Cummings, S. R., Orwoll, E. S. 2015; 63 (11): 2247-2259

  View details for DOI 10.1111/jgs.13788

  View details for Web of Science ID 000365678500002

  View details for PubMedID 26502831

• Pain and falls and fractures in community-dwelling older men AGE AND AGEING Munch, T., Harrison, S. L., Barrett-Connor, E., Lane, N. E., Nevitt, M. C., Schousboe, J. T., Stefanick, M., Cawthon, P. M. 2015; 44 (6): 973-979

  View details for DOI 10.1093/ageing/afv125

  View details for Web of Science ID 000365132300016

• Prospective Analysis of Health and Mortality Risk in Veteran and Non-Veteran Participants in the Women's Health Initiative WOMENS HEALTH ISSUES Weitlauf, J. C., LaCroix, A. Z., Bird, C. E., Woods, N. F., Washington, D. L., Katon, J. G., LaMonte, M. J., Goldstein, M. K., Bassuk, S. S., Sarto, G. E., Stefanick, M. L. 2015; 25 (6): 649-657

  Abstract

  The health of postmenopausal women veterans is a neglected area of study. A stronger empirical evidence base is needed, and would inform the provision of health care for the nearly 1 million U.S. women veterans currently 50 years of age or older. To this end, the present work compares salient health outcomes and risk of all-cause mortality among veteran and non-veteran participants of the Women's Health Initiative (WHI).This study features prospective analysis of long-term health outcomes and mortality risk (average follow-up, 8 years) among the 3,706 women veterans and 141,009 non-veterans who participated in the WHI Observational Study or Clinical Trials. Outcome measurements included confirmed incident cases of cardiovascular disease (CVD), cancer, diabetes, hip fractures, and all-cause mortality.We identified 17,968 cases of CVD, 19,152 cases of cancer, 18,718 cases of diabetes, 2,817 cases of hip fracture, and 13,747 deaths. In Cox regression models adjusted for age, sociodemographic variables, and health risk factors, veteran status was associated with significantly increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95% CI, 1.03-1.23), but not with risk of CVD (HR, 1.00; 95% CI, 0.90-1.11), cancer (HR, 1.04; 95% CI, 0.95-1.14), hip fracture (HR, 1.16; 95% CI, 0.94-1.43), or diabetes (HR, 1.00; 95% CI, 0.89-1.1).Women veterans' postmenopausal health, particularly risk for all-cause mortality, warrants further consideration. In particular, efforts to identify and address modifiable risk factors associated with all-cause mortality are needed.

  View details for DOI 10.1016/j.whi.2015.08.006

  View details for Web of Science ID 000368247700010

  View details for PubMedCentralID PMC4641800

• Factors Associated with Nursing Home Admission after Stroke in Older Women. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Bell, C. L., LaCroix, A. Z., Desai, M., Hedlin, H., Rapp, S. R., Cene, C., Savla, J., Shippee, T., Wassertheil-Smoller, S., Stefanick, M. L., Masaki, K. 2015; 24 (10): 2329-2337

  Abstract

  We examined the social and economic factors associated with nursing home (NH) admission in older women, overall and poststroke.The Women's Health Initiative (WHI) included women aged 50-79 years at enrollment (1993-1998). In the WHI Extension Study (2005-2010), participants annually reported any NH admission in the preceding year. Separate multivariate logistic regression models analyzed social and economic factors associated with long-term NH admission, defined as an admission on 2 or more questionnaires, overall and poststroke.Of 103,237 participants, 8904 (8.6%) reported NH admission (2005-2010); 534 of 2225 (24.0%) women with incident stroke reported poststroke NH admission. Decreased likelihoods of NH admission overall were demonstrated for Asian, Black, and Hispanic women (versus whites, adjusted odds ratio [aOR] = .35-.44, P < .001) and women with higher income (aOR = .75, 95% confidence interval [CI] = .63-.90), whereas increased likelihoods of NH admission overall were seen for women with lower social support (aOR = 1.34, 95% CI = 1.16-1.54) and with incident stroke (aOR = 2.59, 95% CI = 2.15-3.12). Increased odds of NH admission after stroke were demonstrated for women with moderate disability after stroke (aOR = 2.76, 95% CI = 1.73-4.42). Further adjustment for stroke severity eliminated the association found for race/ethnicity, income, and social support.The level of care needed after a disabling stroke may overwhelm social and economic structures in place that might otherwise enable avoidance of NH admission. We need to identify ways to provide care consistent with patients' preferences, even after a disabling stroke.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2015.06.013

  View details for PubMedID 26169547

  View details for PubMedCentralID PMC4592792

• Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-1441

  Abstract

  This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for Web of Science ID 000361757600013

• Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or Both JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Chalhoub, D., Cawthon, P. M., Ensrud, K. E., Stefanick, M. L., Kado, D. M., Boudreau, R., Greenspan, S., Newman, A. B., Zmuda, J., Orwoll, E. S., Cauley, J. A. 2015; 63 (9): 1733-1740

  Abstract

  To test the hypothesis that men and women with low bone mineral density (BMD) and sarcopenia have a higher risk of fracture than those with only one or neither conditions.The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospective observational studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009), respectively.U.S. clinical centers.Men (n = 5,544; mean age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk without assistance, and without bilateral hip replacement.Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0. Participants were classified as having normal BMD and no sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women).Men with low BMD and sarcopenia (hazard ratio (HR)=3.79, 95% confidence interval (CI)=2.65-5.41) and men with low BMD only (HR=1.67, 95% CI=1.45-1.93) but not men with sarcopenia only (HR=1.14, 95% CI=0.62-2.09) had greater risk of fracture than men with normal BMD and no sarcopenia. Women with low BMD and sarcopenia (HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone (HR=2.62, 95% CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture than women with normal BMD and no sarcopenia.Men with low BMD and sarcopenia are at especially high risk of fracture. Sarcopenia alone did not increase fracture risk in either group.

  View details for DOI 10.1111/jgs.13605

  View details for Web of Science ID 000363804800001

  View details for PubMedID 26310882

  View details for PubMedCentralID PMC4625906

• Menopausal symptoms in women with chronic kidney disease. Menopause (New York, N.Y.) Cheung, K. L., Stefanick, M. L., Allison, M. A., LeBlanc, E. S., Vitolins, M. Z., Shara, N., Chertow, G. M., Winkelmayer, W. C., Kurella Tamura, M. 2015; 22 (9): 1006-1011

  Abstract

  This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events.Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68).Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

  View details for DOI 10.1097/GME.0000000000000416

  View details for PubMedID 25628057

• Hormone Use, Reproductive History, and Risk of Lung Cancer The Women's Health Initiative Studies JOURNAL OF THORACIC ONCOLOGY Schwartz, A. G., Ray, R. M., Cote, M. L., Abrams, J., Sokol, R. J., Hendrix, S. L., Chen, C., Chlebowski, R. T., Hubbell, F. A., Kooperberg, C., Manson, J. E., O'Sullivan, M. J., Rohan, T., Stefanick, M. L., Wactawski-Wende, J., Wakelee, H., Simon, M. S. 2015; 10 (7): 1004-1013

  Abstract

  Results from the Women's Health Initiative clinical trials demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy (HT). We conducted a joint analysis of the Women's Health Initiative observational study data and clinical trials data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk.Reproductive history, oral contraceptive use, and postmenopausal HT were evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2467 incident lung cancer cases were ascertained, with median follow-up of 14 years.For all lung cancers, women with previous use of estrogen plus progestin of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend toward decreased risk with increasing age at menopause (ptrend = 0.04) and a trend toward increased risk with increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell lung cancer was associated with age 20-29 years at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy.Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with estrogen receptor expression in the lung should continue as a role for estrogen cannot be ruled out and may hold potential for prevention and treatment strategies.

  View details for DOI 10.1097/JTO.0000000000000558

  View details for Web of Science ID 000356944100004

  View details for PubMedID 25852020

• Calcium and vitamin D supplementation do not influence menopause-related symptoms: Results of the Women's Health Initiative Trial MATURITAS LeBlanc, E. S., Hedlin, H., Qin, F., Desai, M., Wactawski-Wende, J., Perrin, N., Manson, J. E., Johnson, K. C., Masaki, K., Tylavsky, F. A., Stefanick, M. L. 2015; 81 (3): 377-383

  Abstract

  It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms.As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000 mg with vitamin D 400 IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.7 years, participants provided data on menopause-related symptoms via questionnaires. Generalized linear mixed effects techniques were used to address research questions.After excluding participants with missing data (N=2125), we compared menopause-related symptoms at follow-up visits of 17,101 women randomized to CaD with those of 17,056 women given the placebo. Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo (p=0.702). Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo.Our data suggest that supplementation with 1000 mg of calcium plus 400 IU of vitamin D does not influence menopause-related symptoms over an average of 5.7 years of follow-up among postmenopausal women with an average age of 64 at the WHI baseline visit.

  View details for DOI 10.1016/j.maturitas.2015.04.007

  View details for Web of Science ID 000357229600009

  View details for PubMedID 26044075

  View details for PubMedCentralID PMC4469550

• Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analyses of Data From 2 Women's Health Initiative Randomized Clinical Trials. JAMA oncology Chlebowski, R. T., Rohan, T. E., Manson, J. E., Aragaki, A. K., Kaunitz, A., Stefanick, M. L., Simon, M. S., Johnson, K. C., Wactawski-Wende, J., O'Sullivan, M. J., Adams-Campbell, L. L., Nassir, R., Lessin, L. S., Prentice, R. L. 2015; 1 (3): 296-305

  Abstract

  The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use.To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women's Health Initiative (WHI) randomized clinical trials.A total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010.A total of 16 608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E + P) or placebo with a median intervention duration of 5.6 years, and 10 739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years.Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials.In the E + P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials.In the E + P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.

  View details for DOI 10.1001/jamaoncol.2015.0494

  View details for PubMedID 26181174

• Lipoprotein particles and size, total and high molecular weight adiponectin, and leptin in relation to incident coronary heart disease among severely obese postmenopausal women: The Women's Health Initiative Observational Study. BBA clinical Mackey, R. H., McTigue, K. M., Chang, Y. F., Barinas-Mitchell, E., Evans, R. W., Tinker, L. F., Lewis, C. E., Manson, J. E., Stefanick, M. L., Howard, B. V., Phillips, L. S., Liu, S., Kulick, D., Kuller, L. H. 2015; 3: 243-250

  Abstract

  We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women.In a case-cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40 kg/m(2) and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples.In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95%CIs) of 1.55(1.28, 1.88) and (0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P.Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference.Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.

  View details for PubMedID 25825692

  View details for PubMedCentralID PMC4375554

• Circadian Rest-Activity Rhythms Predict Future Increases in Depressive Symptoms Among Community-Dwelling Older Men AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Smagula, S. F., Ancoli-Israel, S., Blackwell, T., Boudreau, R., Stefanick, M. L., Paudel, M. L., Stone, K. L., Cauley, J. A. 2015; 23 (5): 495-505

  Abstract

  Circadian rest-activity rhythms (CARs) have been cross-sectionally associated with depressive symptoms, although no longitudinal research has examined whether CARs are a risk factor for developing depressive symptoms.We examined associations of CARs (measured with actigraphy over a mean of 4.8 days) with depressive symptoms (measured with the Geriatric Depression Scale) among 2,892 community-dwelling older men (mean age: 76.2 ± 5.5 years) from the MrOS Sleep Study who were without cognitive impairment. Among 2,124 men with minimal (0-2) symptoms at baseline, we assessed associations between CAR parameters and increases to mild (3-5) or clinically significant (≥6) symptoms after an average of 1.2 (±0.32) years.Cross-sectional associations between rhythm height parameters were independent of chronic diseases, lifestyle, sleep, and self-reported physical activity covariates. For example, men in the lowest mesor quartile had twice the adjusted odds (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.36-3.04, p = 0.0005) of having prevalent clinically significant symptoms (compared to minimal). Longitudinally, low CAR robustness (being in the lowest quartile of the pseudo-F statistic) was independently associated with increasing odds of developing symptoms (i.e., AOR for having clinically significant depressive symptoms at follow-up = 2.58, 95% CI: 1.11-5.99, p = 0.03).CAR disturbances are indicative of depressive symptomology. Low CAR robustness may independently contribute to the risk of worsening depression symptomology.

  View details for DOI 10.1016/j.jagp.2014.06.007

  View details for Web of Science ID 000352213500008

  View details for PubMedID 25066948

• Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women A Cohort Study From the Women's Health Initiative CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Schmiegelow, M. D., Hedlin, H., Stefanick, M. L., Mackey, R. H., Allison, M., Martin, L. W., Robinson, J. G., Hlatky, M. A. 2015; 8 (3): 309-?

  Abstract

  Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors.We identified 15,288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification.Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus.URL: http://www.clinicaltrial.gov. Unique identifier: NCT00000611.

  View details for DOI 10.1161/CIRCOUTCOMES.114.001563

  View details for Web of Science ID 000354743900013

  View details for PubMedID 25944628

• Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort Study From the Women's Health Initiative. Circulation. Cardiovascular quality and outcomes Schmiegelow, M. D., Hedlin, H., Stefanick, M. L., Mackey, R. H., Allison, M., Martin, L. W., Robinson, J. G., Hlatky, M. A. 2015; 8 (3): 309-316

  Abstract

  Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors.We identified 15,288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification.Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus.URL: http://www.clinicaltrial.gov. Unique identifier: NCT00000611.

  View details for DOI 10.1161/CIRCOUTCOMES.114.001563

  View details for PubMedID 25944628

• Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease in postmenopausal women. Journal of the American Heart Association Schmiegelow, M. D., Hedlin, H., Mackey, R. H., Martin, L. W., Vitolins, M. Z., Stefanick, M. L., Perez, M. V., Allison, M., Hlatky, M. A. 2015; 4 (5)

  Abstract

  It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity.Metabolic abnormalities appeared to convey more cardiovascular risk among black women.

  View details for DOI 10.1161/JAHA.114.001695

  View details for PubMedID 25994446

• Familial Clustering of Breast and Prostate Cancer and Risk of Postmenopausal Breast Cancer in the Women's Health Initiative Study CANCER Beebe-Dimmer, J. L., Yee, C., Cote, M. L., Petrucelli, N., Palmer, N., Bock, C., Lane, D., Agalliu, I., Stefanick, M. L., Simon, M. S. 2015; 121 (8): 1265-1272

  Abstract

  Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations.Analyses of participants in the Women's Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives.There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08).These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman's risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers.

  View details for DOI 10.1002/cncr.29075

  View details for Web of Science ID 000352713100020

  View details for PubMedID 25754547

• Optimal Cutoffs of Obesity Measures in Relation to Cancer Risk in Postmenopausal Women in the Women's Health Initiative Study. Journal of women's health (2002) Heo, M., Kabat, G. C., Strickler, H. D., Lin, J., Hou, L., Stefanick, M. L., Anderson, G. L., Rohan, T. E. 2015; 24 (3): 218-227

  Abstract

  Obesity is a risk factor for several cancers in postmenopausal women. We attempted to determine cutoffs of adiposity measures in relation to risk of obesity-related cancers among postmenopausal women and to examine the effects of hormone therapy (HT) use on the cutoffs, neither of which has been broadly studied.We used data from the Women's Health Initiative cohort (n=144,701) and applied Cox-proportional hazards regressions to each combination of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI], weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist to height ratio). Interactions between the anthropometric measures and HT use were also examined. Cutoffs were determined by applying a grid search followed by a two-fold cross validation method. Survival ROC analysis of 5- and 10-year incidence followed.Breast, colorectal, colon, endometrium, kidney, and all cancers combined were significantly positively associated with all six anthropometric measures, whereas lung cancer among ever smokers was significantly inversely associated with all measures except WHR. The derived cutoffs of each obesity measure varied across cancers (e.g., BMI cutoffs for breast and endometrium cancers were 30 kg/m(2) and 34 kg/m(2), respectively), and also depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10-year cancer incidence were higher among HT never users.Using a panel of different anthropometric measures, we derived optimal cut-offs categorizing populations into high- and low-risk groups, which differed by cancer type and HT use. Although the discrimination abilities of these risk categories were generally poor, the results of this study could serve as a starting point from which to determine adiposity cutoffs for inclusion in risk prediction models for specific cancer types.

  View details for DOI 10.1089/jwh.2014.4977

  View details for PubMedID 25587642

• Caregiving Frequency and Physical Function: The Women's Health Initiative. journals of gerontology. Series A, Biological sciences and medical sciences Rosso, A. L., Lee, B. K., Stefanick, M. L., Kroenke, C. H., Coker, L. H., Woods, N. F., Michael, Y. L. 2015; 70 (2): 210-215

  Abstract

  Informal caregiving is common for older women and can negatively affect health, but its impact on physical function remains unclear. Using inverse probability weighting methods, we quantified the association of caregiving with physical function over 6 years.Study participants were 5,649 women aged 65 years and older at baseline of the Woman's Health Initiative Clinical Trial (multicenter recruitment, 1993-1998) with complete caregiving data and function at baseline and at least one follow-up. Caregiving was self-reported (low-frequency if ≤2 times per week and high-frequency if ≥3 times per week). Performance-based measures of physical function including timed walk (meters/second), grip strength (kilograms), and chair stands (number) were measured at baseline and years 1, 3, and 6. Associations and 95% confidence intervals of baseline caregiving with physical function were estimated by generalized estimating equations with inverse probability weighting by propensity and attrition scores, calculated by logistic regression of baseline health and demographic characteristics.Over follow-up, low-frequency caregivers had higher grip strength when compared with noncaregivers (mean difference = 0.63kg, confidence interval: 0.24, 1.01). There were no observed differences between high-frequency caregivers and noncaregivers on grip strength or for either caregiver group when compared with noncaregivers on walk speed or chair stands. Rates of change in physical function measures did not differ by caregiving status.Caregiving was not associated with poorer physical function in this sample of older women. Low-frequency caregiving was associated with better grip strength at baseline which persisted through follow-up. This study supports the concept that informal caregiving may not have universally negative health consequences.

  View details for DOI 10.1093/gerona/glu104

  View details for PubMedID 25060315

• Risk of breast, endometrial, colorectal, and renal cancers in postmenopausal women in association with a body shape index and other anthropometric measures. Cancer causes & control Kabat, G. C., Xue, X., Kamensky, V., Lane, D., Bea, J. W., Chen, C., Qi, L., Stefanick, M. L., Chlebowski, R. T., Wactawski-Wende, J., Wassertheil-Smoller, S., Rohan, T. E. 2015; 26 (2): 219-229

  Abstract

  A body shape index (ABSI) has been proposed as a possible improvement over waist circumference (WC) as a marker of abdominal adiposity because it removes the correlation of WC with body mass index (BMI) and with height. We assessed the association of ABSI with four obesity-related cancers compared to that of other anthropometric measures of adiposity.We used data from the Women's Health Initiative, a large cohort of postmenopausal women, recruited between 1993 and 1998 and followed until September 2013, to assess the associations of ABSI and other anthropometric measures with risk of cancers of the breast, endometrium, colorectum, and kidney. The four comparison anthropometric measures were BMI, WC, waist circumference-to-height ratio (WHtR), and waist-hip ratio (WHR). Over a median of 12.7 years of follow-up, among 143,901 women, we identified 7,039 invasive breast cancers, 1,157 endometrial cancers, 1,908 colorectal cancers, and 376 kidney cancers. We used Cox proportional hazards models to estimate the association of quintiles of the five measures with risk of the four cancers.Unlike the other anthropometric indices, ABSI was not associated with increased risk of breast or endometrial cancer. BMI and WC were comparable as predictors of breast and endometrial cancer, and these associations were unchanged after mutual adjustment. For colorectal and kidney cancers, ABSI was a significant predictor comparable to BMI; however, WC showed the strongest association with colorectal cancer, and WC, WHtR, and WHR all showed stronger associations with kidney cancer.In contrast to other anthropometric measures, ABSI showed no association with risk of breast or endometrial cancer and was more weakly associated with risk of colorectal and kidney cancers compared to more established measures of central adiposity.

  View details for DOI 10.1007/s10552-014-0501-4

  View details for PubMedID 25430815

• Relationships between dog ownership and physical activity in postmenopausal women. Preventive medicine Garcia, D. O., Wertheim, B. C., Manson, J. E., Chlebowski, R. T., Volpe, S. L., Howard, B. V., Stefanick, M. L., Thomson, C. A. 2015; 70: 33-38

  Abstract

  Positive associations between dog ownership and physical activity in older adults have been previously reported.The objective of this study was to examine cross-sectional associations between dog ownership and physical activity measures in a well-characterized, diverse sample of postmenopausal women.Analyses included 36,984 dog owners (mean age: 61.5years), and 115,645 non-dog owners (mean age: 63.9years) enrolled in a clinical trial or the observational study of the Women's Health Initiative between 1993 and 1998. Logistic regression models were used to test for associations between dog ownership and physical activity, adjusted for potential confounders.Owning a dog was associated with a higher likelihood of walking ≥150min/wk (Odds Ratio, 1.14; 95% Confidence Interval, 1.10-1.17) and a lower likelihood of being sedentary ≥8h/day (Odds Ratio, 0.86; 95% Confidence Interval, 0.83-0.89) as compared to not owning a dog. However, dog owners were less likely to meet ≥7.5MET-h/wk of total physical activity as compared to non-dog owners (Odds Ratio, 1.03; 95% Confidence Interval, 1.00-1.07).Dog ownership is associated with increased physical activity in older women, particularly among women living alone. Health promotion efforts aimed at older adults should highlight the benefits of regular dog walking for both dog owners and non-dog owners.

  View details for DOI 10.1016/j.ypmed.2014.10.030

  View details for PubMedID 25449694

• Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease in postmenopausal women. Journal of the American Heart Association Schmiegelow, M. D., Hedlin, H., Mackey, R. H., Martin, L. W., Vitolins, M. Z., Stefanick, M. L., Perez, M. V., Allison, M., Hlatky, M. A. 2015; 4 (5)

  Abstract

  It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity.Metabolic abnormalities appeared to convey more cardiovascular risk among black women.

  View details for DOI 10.1161/JAHA.114.001695

  View details for PubMedID 25994446

• Smoking behavior and association of melanoma and nonmelanoma skin cancer in the Women's Health Initiative JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Henderson, M. T., Kubo, J. T., Desai, M., David, S. P., Tindle, H., Sinha, A. A., Hou, L., Messina, C., Saquib, N., Stefanick, M. L., Tang, J. Y. 2015; 72 (1): 190-191

  View details for DOI 10.1016/j.jaad.2014.09.024

  View details for Web of Science ID 000346404500053

  View details for PubMedID 25497923

• Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort†. Annals of oncology Wang, A., Kubo, J., Luo, J., Desai, M., Hedlin, H., Henderson, M., Chlebowski, R., Tindle, H., Chen, C., Gomez, S., Manson, J. E., Schwartz, A. G., Wactawski-Wende, J., Cote, M., Patel, M. I., Stefanick, M. L., Wakelee, H. A. 2015; 26 (1): 221-230

  Abstract

  Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work).The Women's Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status.Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58).In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking.NCT00000611.

  View details for DOI 10.1093/annonc/mdu470

  View details for PubMedID 25316260

• Association of the selected dimensions of eudaimonic well-being with healthy survival to 85 years of age in older women INTERNATIONAL PSYCHOGERIATRICS Zaslavsky, O., Rillamas-Sun, E., Woods, N. F., Cochrane, B. B., Stefanick, M. L., Tindle, H., Tinker, L. F., LaCroix, A. Z. 2014; 26 (12): 2081-2091

  View details for DOI 10.1017/S1041610214001768

  View details for Web of Science ID 000344948000018

• Association of the selected dimensions of eudaimonic well-being with healthy survival to 85 years of age in older women. International psychogeriatrics Zaslavsky, O., Rillamas-Sun, E., Woods, N. F., Cochrane, B. B., Stefanick, M. L., Tindle, H., Tinker, L. F., LaCroix, A. Z. 2014; 26 (12): 2081-2091

  Abstract

  Aspects of eudaimonic well-being, such as personal growth (PG) and purpose in life (PL), have been highlighted as important to older adults' health. We investigated the relationship of PG and PL with patterns of survival to the age of 85 years and older.The sample included 8,880 women from the Women's Health Initiative cohort who reached 85 years of age by December 1, 2013, and for whom data on the PG and PL constructs were available. Women were classified into mutually exclusive outcomes: Healthy, Prevalent, Incident, Disabled, and Deceased. PG and PL were each assessed using a modified seven-item measure derived from the Psychological Well-Being scale.Women were most commonly classified as Healthy (38.2%, n = 3,395), followed by Incident (24.4%, n = 2,163), Disabled (19.0%, n = 1,685), Prevalent (14.3%, 1,273), and Deceased (4.1%, n = 364). Women with low PL and PG levels were more likely to have prevalent mobility disability and disease or incident death before the age of 85 years. Specifically, those who reported low levels of PG and PL had a 2.1- and 3.6-fold higher risk, respectively, of death.These findings indicate that even among the oldest old, experience of purposeful life engagement and continuing PG may contribute to better health outcomes.

  View details for DOI 10.1017/S1041610214001768

  View details for PubMedID 25162287

• Non-melanoma skin cancer and NSAID use in women with a history of skin cancer in the Women's Health Initiative. Preventive medicine Wysong, A., Ally, M. S., Gamba, C. S., Desai, M., Swetter, S. M., Seiffert-Sinha, K., Sinha, A. A., Stefanick, M. L., Tang, J. Y. 2014; 69: 8-12

  Abstract

  Evidence for the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on non-melanoma skin cancer (NMSC) risk is inconsistent. We prospectively examined whether regular, inconsistent, or no/low-use of NSAIDs is associated with lower NMSC risk among 54,728 postmenopausal Caucasian women in the Women's Health Initiative Observational Study enrolled between 1993 and 1998.Logistic regression models were used to assess odds of NMSC after adjusting for skin type, sun exposure history and indication for NSAID use.There were 7652 incident cases of NMSC (median follow-up: 6.9years). There was no association between regular NSAID-use and NMSC risk relative to no/low-users. However, in a subgroup analysis of 5325 women with a history of skin cancer (incident NMSC: 1897), odds of NMSC were lower among regular NSAID users whether <5years (OR 0.82, 95% CI: 0.70-0.95) or ≥5years (OR 0.82, 95% CI: 0.69-0.98) of use compared to no/low-users. Inconsistent NSAID use and acetaminophen use were not associated with NMSC risk.Overall, NSAID use was not associated with NMSC risk. However, in women with a history of skin cancer, regular NSAID use was associated with 18% lower odds of NMSC. Future studies on potential chemopreventative effects of NSAIDs should focus on subjects with prior history of NMSC.

  View details for DOI 10.1016/j.ypmed.2014.08.024

  View details for PubMedID 25150382

• Non-melanoma skin cancer and NSAID use in women with a history of skin cancer in the Women's Health Initiative PREVENTIVE MEDICINE Wysong, A., Ally, M. S., Gamba, C. S., Desai, M., Swetter, S. M., Seiffert-Sinha, K., Sinha, A. A., Stefanick, M. L., Tang, J. Y. 2014; 69: 8-12

  Abstract

  Evidence for the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on non-melanoma skin cancer (NMSC) risk is inconsistent. We prospectively examined whether regular, inconsistent, or no/low-use of NSAIDs is associated with lower NMSC risk among 54,728 postmenopausal Caucasian women in the Women's Health Initiative Observational Study enrolled between 1993 and 1998.Logistic regression models were used to assess odds of NMSC after adjusting for skin type, sun exposure history and indication for NSAID use.There were 7652 incident cases of NMSC (median follow-up: 6.9years). There was no association between regular NSAID-use and NMSC risk relative to no/low-users. However, in a subgroup analysis of 5325 women with a history of skin cancer (incident NMSC: 1897), odds of NMSC were lower among regular NSAID users whether <5years (OR 0.82, 95% CI: 0.70-0.95) or ≥5years (OR 0.82, 95% CI: 0.69-0.98) of use compared to no/low-users. Inconsistent NSAID use and acetaminophen use were not associated with NMSC risk.Overall, NSAID use was not associated with NMSC risk. However, in women with a history of skin cancer, regular NSAID use was associated with 18% lower odds of NMSC. Future studies on potential chemopreventative effects of NSAIDs should focus on subjects with prior history of NMSC.

  View details for DOI 10.1016/j.ypmed.2014.08.024

  View details for Web of Science ID 000346221600003

• Vitamin D levels and menopause-related symptoms. Menopause (New York, N.Y.) LeBlanc, E. S., Desai, M., Perrin, N., Wactawski-Wende, J., Manson, J. E., Cauley, J. A., Michael, Y. L., Tang, J., Womack, C., Song, Y., Johnson, K. C., O'Sullivan, M. J., Woods, N., Stefanick, M. L. 2014; 21 (11): 1197-1203

  Abstract

  This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women.A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses.Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10 for fully adjusted models).There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.

  View details for DOI 10.1097/GME.0000000000000238

  View details for PubMedID 24736200

• Trajectories of positive aging: observations from the women's health initiative study. International psychogeriatrics Zaslavsky, O., Cochrane, B. B., Woods, N. F., LaCroix, A. Z., Liu, J., Herting, J. R., Goveas, J. S., Johnson, K. C., Kuller, L. H., Martin, L. W., Michael, Y. L., Robinson, J. G., Stefanick, M., Tinker, L. F. 2014; 26 (8): 1351-1362

  Abstract

  The purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.Women age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.A five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.Aging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.

  View details for DOI 10.1017/S1041610214000593

  View details for PubMedID 24739218

• Obesity, physical activity, and their interaction in incident atrial fibrillation in postmenopausal women. Journal of the American Heart Association Azarbal, F., Stefanick, M. L., Salmoirago-Blotcher, E., Manson, J. E., Albert, C. M., LaMonte, M. J., Larson, J. C., Li, W., Martin, L. W., Nassir, R., Garcia, L., Assimes, T. L., Tharp, K. M., Hlatky, M. A., Perez, M. V. 2014; 3 (4)

  View details for DOI 10.1161/JAHA.114.001127

  View details for PubMedID 25142057

• Obesity, physical activity, and their interaction in incident atrial fibrillation in postmenopausal women. Journal of the American Heart Association Azarbal, F., Stefanick, M. L., Salmoirago-Blotcher, E., Manson, J. E., Albert, C. M., LaMonte, M. J., Larson, J. C., Li, W., Martin, L. W., Nassir, R., Garcia, L., Assimes, T. L., Tharp, K. M., Hlatky, M. A., Perez, M. V. 2014; 3 (4)

  Abstract

  Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF.The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI-ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5-kg/m(2) increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033).Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF.

  View details for DOI 10.1161/JAHA.114.001127

  View details for PubMedID 25142057

• Statins and physical activity in older men: the osteoporotic fractures in men study. JAMA internal medicine Lee, D. S., Markwardt, S., Goeres, L., Lee, C. G., Eckstrom, E., Williams, C., Fu, R., Orwoll, E., Cawthon, P. M., Stefanick, M. L., Mackey, D., Bauer, D. C., Nielson, C. M. 2014; 174 (8): 1263-1270

  Abstract

  Muscle pain, fatigue, and weakness are common adverse effects of statin medications and may decrease physical activity in older men.To determine whether statin use is associated with physical activity, longitudinally and cross-sectionally.Men participating in the Osteoporotic Fractures in Men Study (N = 5994), a multicenter prospective cohort study of community-living men 65 years and older, enrolled between March 2000 and April 2002. Follow-up was conducted through 2009.Statin use as determined by an inventory of medications (taken within the last 30 days). In cross-sectional analyses (n = 4137), statin use categories were users and nonusers. In longitudinal analyses (n = 3039), categories were prevalent users (baseline use and throughout the study), new users (initiated use during the study), and nonusers (never used).Self-reported physical activity at baseline and 2 follow-up visits using the Physical Activity Scale for the Elderly (PASE). At the third visit, an accelerometer measured metabolic equivalents (METs [kilocalories per kilogram per hour]) and minutes of moderate activity (METs ≥3.0), vigorous activity (METs ≥6.0), and sedentary behavior (METs ≤1.5).At baseline, 989 men (24%) were users and 3148 (76%) were nonusers. The adjusted difference in baseline PASE between users and nonusers was -5.8 points (95% CI, -10.9 to -0.7 points). A total of 3039 men met the inclusion criteria for longitudinal analysis: 727 (24%) prevalent users, 845 (28%) new users, and 1467 (48%) nonusers. PASE score declined by a mean (95% CI) of 2.5 (2.0 to 3.0) points per year for nonusers and 2.8 (2.1 to 3.5) points per year for prevalent users, a nonstatistical difference (0.3 [-0.5 to 1.0] points). For new users, annual PASE score declined at a faster rate than nonusers (difference of 0.9 [95% CI, 0.1 to 1.7] points). A total of 3071 men had adequate accelerometry data, 1542 (50%) were statin users. Statin users expended less METs (0.03 [95% CI, 0.02-0.04] METs less) and engaged in less moderate physical activity (5.4 [95% CI, 1.9-8.8] fewer minutes per day), less vigorous activity (0.6 [95% CI, 0.1-1.1] fewer minutes per day), and more sedentary behavior (7.6 [95% CI, 2.6-12.4] greater minutes per day).Statin use was associated with modestly lower physical activity among community-living men, even after accounting for medical history and other potentially confounding factors. The clinical significance of these findings deserves further investigation.

  View details for DOI 10.1001/jamainternmed.2014.2266

  View details for PubMedID 24911216

• Association Between Thyroid Function and Objective and Subjective Sleep Quality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study. Endocrine practice Akatsu, H., Ewing, S. K., Stefanick, M. L., Fink, H. A., Stone, K. L., Barrett-Connor, E., Mehra, R., Ancoli-Israel, S., Redline, S., Hoffman, A. R., For The Osteoporotic Fractures In Men MrOS Research Group 2014; 20 (6): 576-586

  Abstract

  Objective: To determine the association between thyroid hormone levels and sleep quality in community-dwelling men.Methods: Among 5,994 men aged ≥65 years in the Osteoporotic Fractures in Men (MrOS) study, 682 had baseline thyroid function data, normal free thyroxine (FT4) (0.70 ≤ FT4 ≤ 1.85 ng/dL), actigraphy measurements, and were not using thyroid-related medications. Three categories of thyroid function were defined: subclinical hyperthyroid (thyroid-stimulating hormone [TSH] <0.55 mIU/L), euthyroid (TSH, 0.55 to 4.78 mIU/L), and subclinical hypothyroid (TSH >4.78 mIU/L). Objective (total hours of nighttime sleep [TST], sleep efficiency [SE], wake after sleep onset [WASO], sleep latency [SL], number of long wake episodes [LWEP]) and subjective (TST, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score) sleep quality parameters were measured. The association between TSH and sleep quality was examined using linear regression (continuous sleep outcomes) and log-binomial regression (categorical sleep outcomes).Results: Among the 682 men examined, 15 had subclinical hyperthyroidism and 38 had subclinical hypothyroidism. There was no difference in sleep quality between subclinical hypothyroid and euthyroid men. Compared to euthyroid men, subclinical hyperthyroid men had lower mean actigraphy TST (adjusted mean difference [95% confidence interval (CI)], -27.4 [-63.7 to 8.9] minutes), lower mean SE (-4.5% [-10.3% to 1.3%]), and higher mean WASO (13.5 [-8.0 to 35.0] minutes]), whereas 41% had increased risk of actigraphy-measured TST <6 hours (relative risk [RR], 1.41; 95% CI, 0.83 to 2.39), and 83% had increased risk of SL ≥60 minutes (RR, 1.83; 95% CI, 0.65 to 5.14) (all P>.05).Conclusion: Neither subclinical hypothyroidism nor hyperthyroidism is significantly associated with decreased sleep quality.

  View details for DOI 10.4158/EP13282.OR

  View details for PubMedID 24449663

• Modifying effect of obesity on the association between sitting and incident diabetes in post-menopausal women. Obesity Manini, T. M., LaMonte, M. J., Seguin, R. A., Manson, J. E., Hingle, M., Garcia, L., Stefanick, M. L., Rodriguez, B., Sims, S., Song, Y., Limacher, M. 2014; 22 (4): 1133-1141

  Abstract

  To evaluate the association between self-reported daily sitting time and the incidence of type 2 diabetes in a cohort of postmenopausal women.Women (N=88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes > 14.4 years follow-up.Each hour of sitting time was positively associated with increased risk of diabetes [risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02-1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8-11 (RR: 1.08; 95% CI 1.0-1.1), 12-15 (OR: 1.13; 95% CI 1.0-1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0-1.5) hours per day had an increased risk of diabetes compared to women sitting ≤7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet, and alcohol intake), and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations.Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women-a population already at high risk of the disease.

  View details for DOI 10.1002/oby.20620

  View details for PubMedID 24123945

• Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Women's Health Initiative hormone therapy clinical trials. Menopause (New York, N.Y.) Canonico, M., Plu-Bureau, G., O'Sullivan, M. J., Stefanick, M. L., Cochrane, B., Scarabin, P., Manson, J. E. 2014; 21 (3): 214-220

  Abstract

  OBJECTIVE: This study aims to investigate venous thromboembolism (VTE) risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause, as well as any interaction with randomized hormone therapy (HT) assignment, among postmenopausal women. METHODS: Using pooled data from the Women's Health Initiative HT clinical trials including 27,035 postmenopausal women aged 50 to 79 years who had no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause by Cox proportional hazards models. Linear trends, quadratic relationships, and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. RESULTS: During follow-up, 426 women reported a first VTE, including 294 non-procedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected, and there was not a significant association between VTE and age at menarche, age at menopause, parity, oophorectomy, or time since menopause. However, analyses restricted to non-procedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (P < 0.01). Compared with women aged 40 to 49 years at menopause, those who had early menopause (age <40 y) or late menopause (age >55 y) had a significantly increased VTE risk (hazard ratio [95% CI]: 1.8 [1.2-2.7] and 1.5 [1.0-2.4], respectively). CONCLUSIONS: Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for non-procedure-related VTE.

  View details for DOI 10.1097/GME.0b013e31829752e0

  View details for PubMedID 23760439

• International and ethnic variability of falls in older men. Scandinavian journal of public health Karlsson, M. K., Ribom, E. L., Nilsson, J., Karlsson, C., Cöster, M., Vonschewelov, T., Mallmin, H., Ljunggren, O., Ohlsson, C., Mellström, D., Lorentzon, M., Leung, P., Lau, E., Cauley, J. A., Barrett-Connor, E., Stefanick, M. L., Orwoll, E., Rosengren, B. E. 2014; 42 (2): 194-200

  Abstract

  Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.

  View details for DOI 10.1177/1403494813510789

  View details for PubMedID 24259542

• Women's Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy. Menopause (New York, N.Y.) Robbins, J. A., Aragaki, A., Crandall, C. J., Manson, J. E., Carbone, L., Jackson, R., Lewis, C. E., Johnson, K. C., Sarto, G., Stefanick, M. L., Wactawski-Wende, J. 2014; 21 (2): 116-123

  Abstract

  This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT).This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women's Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density.Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density.Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.

  View details for DOI 10.1097/GME.0b013e3182963901

  View details for PubMedID 23799356

• Sedentary Behavior and Mortality in Older Women: The Women's Health Initiative. American journal of preventive medicine Seguin, R., Buchner, D. M., Liu, J., Allison, M., Manini, T., Wang, C., Manson, J. E., Messina, C. R., Patel, M. J., Moreland, L., Stefanick, M. L., LaCroix, A. Z. 2014; 46 (2): 122-135

  Abstract

  Although epidemiologic studies have shown associations between sedentary behavior and mortality, few have focused on older women with adequate minority representation and few have controlled for both physical activity and functional status.The objective of this study was to determine the relationship between sedentary time and total; cardiovascular disease (CVD); coronary heart disease (CHD); and cancer mortality in a prospective, multiethnic cohort of postmenopausal women.The study population included 92,234 women aged 50-79 years at baseline (1993-1998) who participated in the Women's Health Initiative Observational Study through September 2010. Self-reported sedentary time was assessed by questionnaire and examined in 4 categories (≤4, >4-8, ≥8-11, >11 hours). Mortality risks were examined using Cox proportional hazard models adjusting for confounders. Models were also stratified by age, race/ethnicity, body mass index, physical activity, physical function, and chronic disease to examine possible effect modification. Analyses were conducted in 2012-2013.The mean follow-up period was 12 years. Compared with women who reported the least sedentary time, women reporting the highest sedentary time had increased risk of all-cause mortality in the multivariate model (HR=1.12, 95% CI=1.05, 1.21). Results comparing the highest versus lowest categories for CVD, CHD, and cancer mortality were as follows: HR=1.13, 95% CI=0.99, 1.29; HR=1.27, 95% CI=1.04, 1.55; and HR=1.21, 95% CI=1.07, 1.37, respectively. For all mortality outcomes, there were significant linear tests for trend.There was a linear relationship between greater amounts of sedentary time and mortality risk after controlling for multiple potential confounders.

  View details for DOI 10.1016/j.amepre.2013.10.021

  View details for PubMedID 24439345

  View details for PubMedCentralID PMC3896923

• Change in physical activity after a diabetes diagnosis: opportunity for intervention. Medicine and science in sports and exercise Schneider, K. L., Andrews, C., Hovey, K. M., Seguin, R. A., Manini, T., LaMonte, M. J., Margolis, K. L., Waring, M. E., Ning, Y., Sims, S., Ma, Y., Ockene, J., Stefanick, M. L., Pagoto, S. L. 2014; 46 (1): 84-91

  Abstract

  Moderate intensity physical activity is recommended for individuals with diabetes to control glucose and prevent diabetes-related complications. The extent to which a diabetes diagnosis motivates patients to increase physical activity is unclear. This study used data from the Women's Health Initiative Observational Study (baseline data collected from 1993-1998) to examine change in physical activity and sedentary behavior in women who reported a diabetes diagnosis compared to women who did not report diabetes over 7 years of follow-up (up to 2005).Participants (n=84,300) were post-menopausal women who did not report diabetes at baseline [mean age=63.49; standard deviation (SD)=7.34; mean BMI=26.98 kg/m; SD=5.67]. Linear mixed model analyses were conducted adjusting for study year, age, race/ethnicity, BMI, education, family history of diabetes, physical functioning, pain, energy/fatigue, social functioning, depression, number of chronic diseases and vigorous exercise at age 18. Analyses were completed in August 2012.Participants who reported a diabetes diagnosis during follow-up were more likely to report increasing their total physical activity (p=0.002), walking (p<0.001) and number of physical activity episodes (p<0.001) compared to participants who did not report a diabetes diagnosis. On average, participants reporting a diabetes diagnosis reported increasing their total physical activity by 0.49 MET-hours/week, their walking by 0.033 MET-hours/week and their number of physical activity episodes by 0.19 MET-hours/week. No differences in reported sedentary behavior change were observed (p=0.48).A diabetes diagnosis may prompt patients to increase physical activity. Healthcare professionals should consider how best to capitalize on this opportunity to encourage increased physical activity and maintenance.

  View details for DOI 10.1249/MSS.0b013e3182a33010

  View details for PubMedID 23860414

• Use of Medicare Data to Identify Coronary Heart Disease Outcomes in the Women's Health Initiative. Circulation. Cardiovascular quality and outcomes Hlatky, M. A., Ray, R. M., Burwen, D. R., Margolis, K. L., Johnson, K. C., Kucharska-Newton, A., Manson, J. E., Robinson, J. G., Safford, M. M., Allison, M., Assimes, T. L., Bavry, A. A., Berger, J., Cooper-DeHoff, R. M., Heckbert, S. R., Li, W., Liu, S., Martin, L. W., Perez, M. V., Tindle, H. A., Winkelmayer, W. C., Stefanick, M. L. 2014; 7 (1): 157-162

  View details for DOI 10.1161/CIRCOUTCOMES.113.000373

  View details for PubMedID 24399330

• Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative CANCER PREVENTION RESEARCH Thomson, C. A., McCullough, M. L., Wertheim, B. C., Chlebowski, R. T., Martinez, M. E., Stefanick, M. L., Rohan, T. E., Manson, J. E., Tindle, H. A., Ockene, J., Vitolins, M. Z., Wactawski-Wende, J., Sarto, G. E., Lane, D. S., Neuhouser, M. L. 2014; 7 (1): 42-53

  View details for DOI 10.1158/1940-6207.CAPR-13-0258

  View details for Web of Science ID 000329431500006

  View details for PubMedID 24403289

• Use of Medicare data to identify coronary heart disease outcomes in the Women's Health Initiative. Circulation. Cardiovascular quality and outcomes Hlatky, M. A., Ray, R. M., Burwen, D. R., Margolis, K. L., Johnson, K. C., Kucharska-Newton, A., Manson, J. E., Robinson, J. G., Safford, M. M., Allison, M., Assimes, T. L., Bavry, A. A., Berger, J., Cooper-DeHoff, R. M., Heckbert, S. R., Li, W., Liu, S., Martin, L. W., Perez, M. V., Tindle, H. A., Winkelmayer, W. C., Stefanick, M. L. 2014; 7 (1): 157-162

  Abstract

  . Unique identifier: NCT00000611.

  View details for DOI 10.1161/CIRCOUTCOMES.113.000373

  View details for PubMedID 24399330

• Alcohol consumption and risk of melanoma and non-melanoma skin cancer in the Women's Health Initiative CANCER CAUSES & CONTROL Kubo, J. T., Henderson, M. T., Desai, M., Wactawski-Wende, J., Stefanick, M. L., Tang, J. Y. 2014; 25 (1): 1-10

  Abstract

  The relationship between alcohol consumption and preference of alcohol type with hazard of melanoma (MM) and risk of non-melanoma skin cancer (NMSC) was examined in the Women's Health Initiative (WHI) Observational Study (OS).A prospective cohort of 59,575 White postmenopausal women in the WHI OS (mean age 63.6) was analyzed. Cox proportional hazards models and logistic regression techniques were used to assess the hazard and risk of physician-adjudicated MM and self-reported NMSC, respectively, after adjusting for potential confounders including measures of sun exposure and skin type.Over 10.2 mean years of follow-up, 532 MM cases and 9,593 NMSC cases occurred. A significant relationship between amount of alcohol consumed and both MM and NMSC was observed, with those who consume 7+ drinks per week having a higher hazard of MM (HR 1.64 (1.09, 2.49), p global = 0.0013) and higher risk of NMSC (OR 1.23 (1.11, 1.36), p global < 0.0001) compared to non-drinkers. Lifetime alcohol consumption was also positively associated with hazard of MM (p = 0.0011) and risk of NMSC (p < 0.0001). Further, compared to non-drinkers, a preference for either white wine or liquor was associated with an increased hazard of MM (HR 1.52 (1.02, 2.27) for white wine; HR 1.65 (1.07, 2.55) for liquor) and risk of NMSC (OR 1.16 (1.05, 1.28) for white wine; OR 1.26 (1.13, 1.41) for liquor).Higher current alcohol consumption, higher lifetime alcohol consumption, and a preference for white wine or liquor were associated with increased hazard of MM and risk of NMSC.

  View details for DOI 10.1007/s10552-013-0280-3

  View details for Web of Science ID 000329351700001

  View details for PubMedID 24173533

• Nutrition and physical activity cancer prevention guidelines, cancer risk, and mortality in the women's health initiative. Cancer prevention research Thomson, C. A., McCullough, M. L., Wertheim, B. C., Chlebowski, R. T., Martinez, M. E., Stefanick, M. L., Rohan, T. E., Manson, J. E., Tindle, H. A., Ockene, J., Vitolins, M. Z., Wactawski-Wende, J., Sarto, G. E., Lane, D. S., Neuhouser, M. L. 2014; 7 (1): 42-53

  Abstract

  Healthy lifestyle behaviors are recommended to reduce cancer risk and overall mortality. Adherence to cancer-preventive health behaviors and subsequent cancer risk has not been evaluated in a diverse sample of postmenopausal women. We examined the association between the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines score and risk of incident cancer, cancer-specific mortality, and all-cause mortality in 65,838 postmenopausal women enrolled in the Women's Health Initiative Observational Study. ACS guidelines scores (0-8 points) were determined from a combined measure of diet, physical activity, body mass index (current and at age 18 years), and alcohol consumption. After a mean follow-up of 12.6 years, 8,632 incident cancers and 2,356 cancer deaths were identified. The highest ACS guidelines scores compared with the lowest were associated with a 17% lower risk of any cancer [HR, 0.83; 95% confidence interval (CI), 0.75-0.92], 22% lower risk of breast cancer (HR, 0.78; 95% CI, 0.67-0.92), 52% lower risk of colorectal cancer (HR, 0.48; 95% CI, 0.32-0.73), 27% lower risk of all-cause mortality, and 20% lower risk of cancer-specific mortality (HR, 0.80; 95% CI, 0.71-0.90). Associations with lower cancer incidence and mortality were generally strongest among Asian, black, and Hispanic women and weakest among non-Hispanic whites. Behaviors concordant with Nutrition and Physical Activity Cancer Prevention Guidelines were associated with lower risk of total, breast, and colorectal cancers and lower cancer-specific mortality in postmenopausal women.

  View details for DOI 10.1158/1940-6207.CAPR-13-0258

  View details for PubMedID 24403289

• Does CHA2DS2-VASc improve stroke risk stratification in postmenopausal women with atrial fibrillation? American journal of medicine Abraham, J. M., Larson, J., Chung, M. K., Curtis, A. B., Lakshminarayan, K., Newman, J. D., Perez, M., Rexrode, K., Shara, N. M., Solomon, A. J., Stefanick, M. L., Torner, J. C., Wilkoff, B. L., Wassertheil-Smoller, S. 2013; 126 (12): 1143 e1-8

  Abstract

  Risk stratification of atrial fibrillation patients with a congestive heart failure (C), hypertension (H), age ≥ 75 (A), diabetes (D), stroke or transient ischemic attack (TIA) (S2) (CHADS2) score of <2 remains imprecise, particularly in women. Our objectives were to validate the CHADS2 and congestive heart failure (C), hypertension (H), age ≥ 75 (A2), diabetes (D), stroke, TIA or prior thromboembolic disease (S2)- vascular disease (V), age 65-74 (A), female gender (S) (CHA2DS2-VASc) stroke risk scores in a healthy cohort of American women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk-stratifies individuals with a CHADS2 score of <2.We identified a cohort of 5981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9 ± 7.2 years) enrolled in the Women's Health Initiative and followed for a median of 11.8 years. Univariate and multivariate proportional hazards analyses were used to examine these 2 risk scores, with main outcome measures being annualized event rates of ischemic stroke or transient ischemic attack stratified by risk score.Annualized stroke/transient ischemic attack rates ranged from 0.36% to 2.43% with increasing CHADS2 score (0-4+) (hazard ratio [HR] 1.57; 95% confidence interval [CI], 1.45-1.71 for each 1-point increase) and 0.20%-2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50; 95% CI, 1.41-1.60 for each 1-point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67 (95% CI, 0.65-0.69) versus 0.65 (95% CI, 0.62-0.67), P <.01. For CHADS2 scores <2, stroke risk almost doubled with every additional CHA2DS2-VASc point.Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk in postmenopausal women with atrial fibrillation, CHA2DS2-VASc further risk-stratifies patients with a CHADS2 score <2.

  View details for DOI 10.1016/j.amjmed.2013.05.023

  View details for PubMedID 24139523

• Does CHA2DS2-VASc Improve Stroke Risk Stratification in Postmenopausal Women with Atrial Fibrillation? American journal of medicine Abraham, J. M., Larson, J., Chung, M. K., Curtis, A. B., Lakshminarayan, K., Newman, J. D., Perez, M., Rexrode, K., Shara, N. M., Solomon, A. J., Stefanick, M. L., Torner, J. C., Wilkoff, B. L., Wassertheil-Smoller, S. 2013; 126 (12): 1143 e1-8

  View details for DOI 10.1016/j.amjmed.2013.05.023

  View details for PubMedID 24139523

• Lower Skin Cancer Risk in Women with Higher Body Mass Index: The Women's Health Initiative Observational Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Tang, J. Y., Henderson, M. T., Hernandez-Boussard, T., Kubo, J., Desai, M., Sims, S. T., Aroda, V., Thomas, F., McTiernan, A., Stefanick, M. L. 2013; 22 (12): 2412-2415

  Abstract

  The unclear relationship of obesity to incident melanoma and nonmelanoma skin cancer (NMSC) risks was evaluated in the large, geographically diverse longitudinal, prospective Women's Health Initiative (WHI) observational study. Risks of melanoma and NMSC in normal weight women were compared with risks in overweight [body mass index (BMI) = 25-29.0 kg/m(2)] and obese (BMI ≥ 30 kg/m(2)) women, using Cox proportional hazards models for melanoma and logistic regression for NMSC. Over a mean 9.4 years of follow-up, there were 386 melanoma and 9,870 NSMC cases. Risk of melanoma did not differ across weight categories (P = 0.86), whereas in fully adjusted models, NMSC risk was lower in overweight [OR, 0.93; 95% confidence interval (CI), 0.89-0.99] and obese (OR, 0.85; 95% CI, 0.80-0.91) women (P < 0.001). Excess body weight was not associated with melanoma risk in postmenopausal women but was inversely associated with NMSC risk, possibly due to lower sun exposure in overweight and obese women. This supports previous work demonstrating the relationship between excess body weight and skin cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2412-5. ©2013 AACR.

  View details for DOI 10.1158/1055-9965.EPI-13-0647

  View details for PubMedID 24042260

• Women's health initiative view of estrogen avoidance and all-cause mortality. American journal of public health Prentice, R. L., Manson, J. E., Anderson, G. L., LaCroix, A. Z., Shumaker, S. A., Chlebowski, R. T., Howard, B. V., Stefanick, M. L., Jackson, R. D., Wactawski-Wende, J., Rossouw, J. E. 2013; 103 (12)

  View details for DOI 10.2105/AJPH.2013.301604

  View details for PubMedID 24134350

• Mortality risk in former smokers with breast cancer: Pack-years vs. smoking status. International journal of cancer. Journal international du cancer Saquib, N., Stefanick, M. L., Natarajan, L., Pierce, J. P. 2013; 133 (10): 2493-2497

  Abstract

  It is unclear why successful quitting at time of breast cancer diagnosis should remove risk from a significant lifetime of smoking. Studies concluding this may be biased by how smoking is measured in many epidemiological cohorts. In the late 1990s, a randomized trial of diet and breast cancer outcomes enrolled early-stage female breast cancer survivors diagnosed within the previous 4 years. Smoking history and key covariate measures were available at study entry for 2,953 participants. Participants were followed for an average of 7.3 years (96% response rate). There were 10.1% deaths (83% from breast cancer). At enrollment, 55.2% were never smokers, 41.2% former smokers and 4.6% current smokers. Using current smoking status in a Cox regression, there was no increased risk for former smokers for either all-cause mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI) = 0.87-1.41; p-value = 0.42) or breast cancer mortality. However, when we categorized on extensive lifetime exposure, former smokers with 20+ pack-years of smoking (25.8%) had a significantly higher risk of both all-cause (HR = 1.77; 95% CI = 1.17-2.48; p-value = 0.0007) and breast cancer-specific mortality (HR = 1.62; 95% CI = 1.11-2.37; p-value = 0.01). Lifetime smoking exposure, not current status, should be used to assess mortality risk among former smokers.

  View details for DOI 10.1002/ijc.28241

  View details for PubMedID 23649774

• Relation between self-recalled childhood physical activity and adult physical activity: The women's health initiative. Open journal of epidemiology Goodman, D., Park, H. L., Stefanick, M., Leblanc, E., Bea, J., Qi, L., Kapphahn, K., LaMonte, M., Manini, T., Desai, M., Anton-Culver, H. 2013; 3 (4): 224-231

  Abstract

  Evidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity.48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 - 14, and 15 - 19.In this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood.It is important for researchers to understand the influence of adult characteristics on reported childhood physical activity.

  View details for PubMedID 26877895

  View details for PubMedCentralID PMC4749265

• Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women's Health Initiative Randomized Trials JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Manson, J. E., Chlebowski, R. T., Stefanick, M. L., Aragaki, A. K., Rossouw, J. E., Prentice, R. L., Anderson, G., Howard, B. V., Thomson, C. A., LaCroix, A. Z., Wactawski-Wende, J., Jackson, R. D., Limacher, M., Margolis, K. L., Wassertheil-Smoller, S., Beresford, S. A., Cauley, J. A., Eaton, C. B., Gass, M., Hsia, J., Johnson, K. C., Kooperberg, C., Kuller, L. H., Lewis, C. E., Liu, S., Martin, L. W., Ockene, J. K., O'Sullivan, M. J., Powell, L. H., Simon, M. S., Van Horn, L., Vitolins, M. Z., Wallace, R. B. 2013; 310 (13): 1353-1368

  Abstract

  Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up.A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010.Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death.During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10,000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials.Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.clinicaltrials.gov Identifier: NCT00000611.

  View details for DOI 10.1001/jama.2013.278040

  View details for Web of Science ID 000325098100021

  View details for PubMedID 24084921

• Abdominal Myosteatosis Is Independently Associated with Hyperinsulinemia and Insulin Resistance Among Older Men Without Diabetes OBESITY Miljkovic, I., Cauley, J. A., Wang, P. Y., Holton, K. F., Lee, C. G., Sheu, Y., Barrett-Connor, E., Hoffman, A. R., Lewis, C. B., Orwoll, E. S., Stefanick, M. L., Strotmeyer, E. S., Marshall, L. M. 2013; 21 (10): 2118-2125

  Abstract

  OBJECTIVE: Skeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of Type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity. DESIGN AND METHODS: The association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal, and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 nondiabetic Caucasian men aged 65+ was evaluated. Abdominal IMAT, visceral AT (VAT), and subcutaneous AT (SAT) (cm(3) ) were measured by quantitative computed tomography at the L4-L5 intervertebral space. RESULTS: In age, study site, height, and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin, and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as duel-energy x-ray absorptiometry (DXA) measured total body fat, VAT, or SAT in separate models (all P < 0.009). CONCLUSIONS: A previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men was indicated. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups.

  View details for DOI 10.1002/oby.20346

  View details for Web of Science ID 000325427300021

  View details for PubMedID 23408772

  View details for PubMedCentralID PMC3661705

• Calcium Plus Vitamin D Supplementation and Joint Symptoms in Postmenopausal Women in the Women's Health Initiative Randomized Trial. Journal of the Academy of Nutrition and Dietetics Chlebowski, R. T., Pettinger, M., Johnson, K. C., Wallace, R., Womack, C., Mossavar-Rahmani, Y., Stefanick, M., Wactawski-Wende, J., Carbone, L., Lu, B., Eaton, C., Walitt, B., Kooperberg, C. L. 2013; 113 (10): 1302-1310

  Abstract

  Low vitamin D intake and levels have been associated with increased joint symptoms in some observational studies but the findings are mixed and evidence from randomized trials sparse.To evaluate the influence of supplemental calcium and vitamin D on joint symptoms in the Women's Health Initiative randomized, placebo-controlled, clinical trial.In post hoc analyses, the results of the Women's Health Initiative randomized clinical trial in which 36,282 postmenopausal women were randomized to receive calcium carbonate (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were examined in the 6% subgroup of 1,911 participants, oversampled for minorities, who had serial joint symptom assessment. Qualitative information on joint pain and joint swelling was collected by questionnaire before entry and 2 years after randomization. Logistic regression models were used to compare the occurrence and severity of joint symptoms across randomization groups.At baseline, total calcium and vitamin D intakes from diet and supplements were similar in the two randomization groups. In addition, both joint pain (reported by 73%) and joint swelling (reported by 34%) were commonly reported and comparable in the supplement and placebo groups. Two years after randomization, no statistically significant differences between supplement and placebo groups were seen for joint pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo groups, respectively) or joint swelling frequency (34.6% compared with 32.4% [P=0.29], respectively) or in severity scores for either outcome. Subgroup analyses suggested study participants also using nonprotocol calcium supplements at study entry may have less joint pain with supplement group randomization (interaction P=0.02).Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg calcium carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms.

  View details for DOI 10.1016/j.jand.2013.06.007

  View details for PubMedID 23954097

• Preference for wine is associated with lower hip fracture incidence in post-menopausal women BMC WOMENS HEALTH Kubo, J. T., Stefanick, M. L., Robbins, J., Wactawski-Wende, J., Cullen, M. R., Freiberg, M., Desai, M. 2013; 13

  View details for DOI 10.1186/1472-6874-13-36

  View details for Web of Science ID 000324754800001

• Low-Fat Diet and Skin Cancer Risk: The Women's Health Initiative Randomized Controlled Dietary Modification Trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Gamba, C. S., Stefanick, M. L., Shikany, J. M., Larson, J., Linos, E., Sims, S. T., Marshall, J., Van Horn, L., Zeitouni, N., Tang, J. Y. 2013; 22 (9): 1509-1519

  Abstract

  Background: Large cohort studies have reported no relationship between dietary fat and nonmelanoma skin cancer (NMSC), although a low-fat diet intervention reduced NMSC risk in a small clinical trial. In animal studies, skin tumor development has been reduced by low-fat diet. We evaluated the effect of a low-fat dietary pattern on NMSC and melanoma in the Women's Health Initiative Dietary Modification trial. Methods: Postmenopausal women aged 50 to 79 years (N=48,835) were randomly assigned to the low-fat dietary pattern intervention (N=19,541) or comparison group (N=29,294). The intervention goals included decreasing fat intake to ≤20% of calories, increasing vegetable and fruit intake, and increasing grain intake. Self-reported incident NMSC (N=4,907) and physician-adjudicated incident melanoma (N=279) were ascertained every 6 months. Results: Over 8.1 years of follow-up, the low-fat diet intervention did not affect overall incidence of NMSC (hazard ratio [HR] 0.98, 95% confidence interval [CI]: 0.92-1.04) or melanoma (HR 1.04, 95% CI: 0.82-1.32). In subgroup analyses of melanoma risk, baseline fat intake interacted significantly with group assignment (Pinteraction=0.006). Among women with higher baseline fat intake, the dietary intervention significantly increased risk (HR 1.48; 95% CI: 1.06-2.07), whereas, among women with lower baseline fat intake, the intervention tended to reduce melanoma risk (HR 0.72, 95% CI: 0.50-1.02). Conclusions: In this large randomized trial, a low-fat dietary pattern did not affect overall incidence of NMSC or melanoma. Impact: A low-fat diet does not reduce incidence of NMSC, but an interaction between baseline fat intake and dietary intervention on melanoma risk warrants further investigation.

  View details for DOI 10.1158/1055-9965.EPI-13-0341

  View details for Web of Science ID 000324674500004

  View details for PubMedID 23697610

• African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative. American heart journal Perez, M. V., Hoffmann, T. J., Tang, H., Thornton, T., Stefanick, M. L., Larson, J. C., Kooperberg, C., Reiner, A. P., Caan, B., Iribarren, C., Risch, N. 2013; 166 (3): 566-572 e1

  View details for DOI 10.1016/j.ahj.2013.05.024

  View details for PubMedID 24016508

• African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative. American heart journal Perez, M. V., Hoffmann, T. J., Tang, H., Thornton, T., Stefanick, M. L., Larson, J. C., Kooperberg, C., Reiner, A. P., Caan, B., Iribarren, C., Risch, N. 2013; 166 (3): 566-572

  Abstract

  Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses.Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort.African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans.

  View details for DOI 10.1016/j.ahj.2013.05.024

  View details for PubMedID 24016508

• Relationships among changes in C-reactive protein and cardiovascular disease risk factors with lifestyle interventions NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES Young, D., CAMHI, S., Wu, T., Hagberg, J., Stefanick, M. 2013; 23 (9): 857-863

  Abstract

  BACKGROUND AND AIMS: Inflammation plays a role in the development of cardiovascular disease (CVD). Elevated levels of the inflammatory marker, C-reactive protein (CRP), are cross-sectionally associated with traditional CVD risk factors and are being considered as an emerging CVD risk factor. In a secondary data analysis, we examined changes in CRP and several CVD risk factors after one-year diet and physical activity interventions to assess whether CRP changed concurrently with other risk factors, or was independent of the traditional risk factors. METHODS AND RESULTS: Data were analyzed from 143 men and 133 women with dyslipidemia who were randomized to one-year interventions of low-fat diet only, physical activity only, diet plus physical activity, or control. Plasma high-sensitivity CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting and 2-hr blood glucose and insulin, blood pressure (BP), and waist circumference were obtained at baseline and follow-up. Multiple linear regression models were used to predict CRP change based on other risk factor changes, controlling for age, race, alcohol intake, and hormone replacement therapy. Treatment groups were combined for analysis. Baseline mean (SD) CRP levels were 1.3 ± 1.3 (men) and 1.9 ± 1.8 mg/L (women), with mean changes of -0.11 ± 1.3 and -0.17 ± 1.5 mg/L, respectively. Plasma CRP change was negatively associated with TG change in men (p = 0.003) and women (p = 0.05), positively associated with change in systolic BP in men (p = 0.01), but was not associated with changes in the other risk factors. CONCLUSION: Dietary and/or physical activity induced changes in CRP may be largely independent of traditional CVD risk factors in persons with dyslipidemia.

  View details for DOI 10.1016/j.numecd.2012.05.003

  View details for Web of Science ID 000324538200009

  View details for PubMedID 22831953

• Long-Term Effects on Cognitive Function of Postmenopausal Hormone Therapy Prescribed to Women Aged 50 to 55 Years JAMA INTERNAL MEDICINE Espeland, M. A., Shumaker, S. A., Leng, I., Manson, J. E., Brown, C. M., LeBlanc, E. S., Vaughan, L., Robinson, J., Rapp, S. R., Goveas, J. S., Lane, D., Wactawski-Wende, J., Stefanick, M. L., Li, W., Resnick, S. M. 2013; 173 (15): 1429-1436

  Abstract

  Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women.To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function.Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999.Forty academic research centers.The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years.The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years.The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory.Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (−0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 (−0.33 to −0.02) and −0.25 (−0.42 to −0.08), respectively; however, this may be a chance finding.CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term.clinicaltrials.gov Identifier: NCT01124773.

  View details for DOI 10.1001/jamainternmed.2013.7727

  View details for Web of Science ID 000324440400008

  View details for PubMedID 23797469

• Changes in physical activity and body composition in postmenopausal women over time. Medicine and science in sports and exercise Sims, S. T., Kubo, J., Desai, M., Bea, J., Beasley, J. M., Manson, J. E., Allison, M., Seguin, R. A., Chen, Z., Michael, Y. L., Sullivan, S. D., Beresford, S., Stefanick, M. L. 2013; 45 (8): 1486-1492

  Abstract

  PURPOSE: Higher physical activity (PA) has been associated with greater attenuation of body-fat gain and preservation of lean mass across the lifespan. These analyses aimed to determine relationships of change in PA to changes in fat and lean body mass in a longitudinal prospective study of postmenopausal women. METHODS: Among 11,491 women enrolled at three Women's Health Initiative (WHI) clinical centers were selected to undergo dual-energy x-ray absorptiometry (DXA), 8,352 had baseline body composition measurements, with at least one repeated measure at yr 1, 3, and 6. PA data were obtained by self-report at baseline, 3 and 6 yr of follow-up. Time-varying PA impact on change in lean and fat mass during the six-yr study period for age groups (50-59y, 60-69y, 70- 79y) was estimated using mixed effects linear regression. RESULTS: Baseline PA and body composition differed significantly among the three age groups. The association of change in fat mass from baseline and time-varying PA differed across the three age groups (p=0.0006). In women aged 50-59, gain in fat mass from baseline was attenuated with higher levels of physical activity. Women aged 70-79 lost fat mass at all PA levels. In contrast, change in lean mass from baseline and time-varying PA did not differ by age group (p=0.1935). CONCLUSIONS: The association between PA and change in fat mass varies by age group, with younger, but not older, women benefitting from higher levels of aerobic PA. Higher levels of aerobic activity are not associated with changes in lean mass, which tends to decrease in older women regardless of activity level. Greater attention to resistance training exercises may be needed to prevent lean mass loss as women age.

  View details for DOI 10.1249/MSS.0b013e31828af8bd

  View details for PubMedID 23439422

• Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study. Heart Perez, M. V., Wang, P. J., Larson, J. C., Soliman, E. Z., Limacher, M., Rodriguez, B., Klein, L., Manson, J. E., Martin, L. W., Prineas, R., Connelly, S., Hlatky, M., Wassertheil-Smoller, S., Stefanick, M. L. 2013; 99 (16): 1173-1178

  Abstract

  OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

  View details for DOI 10.1136/heartjnl-2013-303798

  View details for PubMedID 23756655

• Relationship of Sedentary Behavior and Physical Activity to Incident Cardiovascular Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chomistek, A. K., Manson, J. E., Stefanick, M. L., Lu, B., Sands-Lincoln, M., Going, S. B., Garcia, L., Allison, M. A., Sims, S. T., LaMonte, M. J., Johnson, K. C., Eaton, C. B. 2013; 61 (23): 2346-2354

  Abstract

  OBJECTIVES: The aim was to examine the independent and joint associations of sitting time and physical activity with risk of incident cardiovascular disease (CVD). BACKGROUND: Sedentary behavior is recognized as a distinct construct beyond lack of leisure-time physical activity, but limited data exists on the interrelationship between these two components of energy balance. METHODS: Participants in the prospective Women's Health Initiative Observational Study (N = 71,018), aged 50-79 and free of CVD at baseline (1993-1998), provided information on sedentary behavior, defined as hours of sitting per day, and usual physical activity at baseline and during follow-up through September 2010. First CVD (coronary heart disease or stroke) events were centrally adjudicated. RESULTS: Sitting ≥ 10 hours/day compared to ≤ 5 hours/day was associated with increased CVD risk (HR=1.18, 95% CI 1.09, 1.29) in multivariable models including physical activity. Low physical activity was also associated with higher CVD risk (P,trend <0.001). When women were cross-classified by sitting time and physical activity (P,interaction = 0.94), CVD risk was highest in inactive women (≤1.7 MET-hrs/week) who also reported ≥10 hrs/day of sitting. Results were similar for CHD and stroke when examined separately. Associations between prolonged sitting and risk of CVD were stronger in overweight versus normal weight women and women aged 70 years and older compared to younger women. CONCLUSIONS: Prolonged sitting time was associated with increased CVD risk, independent of leisure-time physical activity, in postmenopausal women without a history of CVD. A combination of low physical activity and prolonged sitting augments CVD risk.

  View details for DOI 10.1016/j.jacc.2013.03.031

  View details for Web of Science ID 000320601400007

• Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial. Menopause (New York, N.Y.) Chlebowski, R. T., Cirillo, D. J., Eaton, C. B., Stefanick, M. L., Pettinger, M., Carbone, L. D., Johnson, K. C., Simon, M. S., Woods, N. F., Wactawski-Wende, J. 2013; 20 (6): 600-608

  Abstract

  OBJECTIVE: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. METHODS: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. RESULTS: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. CONCLUSIONS: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.

  View details for DOI 10.1097/GME.0b013e31828392c4

  View details for PubMedID 23511705

• Sleep Duration, Insomnia, and Coronary Heart Disease Among Postmenopausal Women in the Women's Health Initiative. Journal of women's health (2002) Sands-Lincoln, M., Loucks, E. B., Lu, B., Carskadon, M. A., Sharkey, K., Stefanick, M. L., Ockene, J., Shah, N., Hairston, K. G., Robinson, J. G., Limacher, M., Hale, L., Eaton, C. B. 2013; 22 (6): 477-486

  Abstract

  Abstract Background: Long and short sleep duration are associated with increased risk for coronary heart disease (CHD) and cardiovascular disease (CVD); however, evidence is inconsistent. We sought to identify whether self-reported sleep duration and insomnia, based on a validated questionnaire, are associated with increased incident CHD and CVD among postmenopausal women. Methods: Women's Health Initiative Observational Study Participants (N=86,329; 50-79 years) who reported on sleep at baseline were followed for incident CVD events. Associations of sleep duration and insomnia with incident CHD and CVD were evaluated using Cox proportional hazards models over 10.3 years. Results: Women with high insomnia scores had elevated risk of CHD (38%) and CVD (27%) after adjustment for age and race, and in fully adjusted models (hazard ratio [HR]=1.19, 95% confidence interval [CI] 1.09-1.30; 1.11 95% CI 1.03-2.00). Shorter (≤5 hours) and longer (≥10 hours) sleep duration demonstrated significantly higher incident CHD (25%) and CVD (19%) in age- and race-adjusted models, but this was not significant in fully adjusted models. Formal tests for interaction indicated significant interactions between sleep duration and insomnia for risk of CHD (p<0.01) and CVD (p=0.02). Women with high insomnia scores and long sleep demonstrated the greatest risk of incident CHD compared to midrange sleep duration (HR=1.93, 95% CI 1.06-3.51) in fully adjusted models. Conclusions: Sleep duration and insomnia are associated with CHD and CVD risk, and may interact to cause almost double the risk of CHD and CVD. Additional research is needed to understand how sleep quality modifies the association between prolonged sleep and cardiovascular outcomes.

  View details for DOI 10.1089/jwh.2012.3918

  View details for PubMedID 23651054

• Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Chlebowski, R. T., Cirillo, D. J., Eaton, C. B., Stefanick, M. L., Pettinger, M., Carbone, L. D., Johnson, K. C., Simon, M. S., Woods, N. F., Wactawski-Wende, J. 2013; 20 (6): 600-608

  View details for DOI 10.1097/gme.0b013e31828392c4

  View details for Web of Science ID 000319659300005

• Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women BMC PUBLIC HEALTH Saquib, N., Brunner, R., Kubo, J., Tindle, H., Kroenke, C., Desai, M., Daviglus, M. L., Allen, N., Martin, L. W., Robinson, J., Stefanick, M. L. 2013; 13

  View details for DOI 10.1186/1471-2458-13-468

  View details for Web of Science ID 000321500700001

• Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. Journal of the National Cancer Institute Chlebowski, R. T., Manson, J. E., Anderson, G. L., Cauley, J. A., Aragaki, A. K., Stefanick, M. L., Lane, D. S., Johnson, K. C., Wactawski-Wende, J., Chen, C., Qi, L., Yasmeen, S., Newcomb, P. A., Prentice, R. L. 2013; 105 (8): 526-535

  Abstract

  In the Women's Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.

  View details for DOI 10.1093/jnci/djt043

  View details for PubMedID 23543779

• Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women The Women's Health Initiative CANCER Gamba, C. A., Swetter, S. M., Stefanick, M. L., Kubo, J., Desai, M., Spaunhurst, K. M., Sinha, A. A., Asgari, M. M., Sturgeon, S., Tang, J. Y. 2013; 119 (8): 1562-1569

  Abstract

  Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ≥ 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ≥ 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk.Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

  View details for DOI 10.1002/cncr.27817

  View details for Web of Science ID 000317618700016

  View details for PubMedID 23483536

• Physical Activity Assessment: Biomarkers and Self-Report of Activity-Related Energy Expenditure in the WHI AMERICAN JOURNAL OF EPIDEMIOLOGY Neuhouser, M. L., Di, C., Tinker, L. F., Thomson, C., Sternfeld, B., Mossavar-Rahmani, Y., Stefanick, M. L., Sims, S., Curb, J. D., LaMonte, M., Seguin, R., Johnson, K. C., Prentice, R. L. 2013; 177 (6): 576-585

  Abstract

  We used a biomarker of activity-related energy expenditure (AREE) to assess measurement properties of self-reported physical activity and to determine the usefulness of AREE regression calibration equations in the Women's Health Initiative. Biomarker AREE, calculated as the total energy expenditure from doubly labeled water minus the resting energy expenditure from indirect calorimetry, was assessed in 450 Women's Health Initiative participants (2007-2009). Self-reported AREE was obtained from the Arizona Activity Frequency Questionnaire (AAFQ), the 7-Day Physical Activity Recall (PAR), and the Women's Health Initiative Personal Habits Questionnaire (PHQ). Eighty-eight participants repeated the protocol 6 months later. Reporting error, measured as log(self-report AREE) minus log(biomarker AREE), was regressed on participant characteristics for each instrument. Body mass index was associated with underreporting on the AAFQ and PHQ but overreporting on PAR. Blacks and Hispanics underreported physical activity levels on the AAFQ and PAR, respectively. Underreporting decreased with age for the PAR and PHQ. Regressing logbiomarker AREE on logself-reported AREE revealed that self-report alone explained minimal biomarker variance (R(2) = 7.6, 4.8, and 3.4 for AAFQ, PAR, and PHQ, respectively). R(2) increased to 25.2, 21.5, and 21.8, respectively, when participant characteristics were included. Six-month repeatability data adjusted for temporal biomarker variation, improving R(2) to 79.4, 67.8, and 68.7 for AAFQ, PAR, and PHQ, respectively. Calibration equations "recover" substantial variation in average AREE and valuably enhance AREE self-assessment.

  View details for DOI 10.1093/aje/kws269

  View details for Web of Science ID 000316374500013

  View details for PubMedID 23436896

• Coronary heart disease events in the Women's Health Initiative hormone trials: effect modification by metabolic syndrome: A nested case-control study within the Women's Health Initiative randomized clinical trials MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Wild, R. A., Wu, C., Curb, J. D., Martin, L. W., Phillips, L., Stefanick, M., Trevisan, M., Manson, J. E. 2013; 20 (3): 254-260

  Abstract

  Our objective was to determine whether metabolic syndrome (MetS) or its components modified the effect of hormone therapy (HT) on the risk of coronary heart disease (CHD) events in the Women's Health Initiative clinical trials.We performed a nested case-control study of incident CHD events during the first 4 years of follow-up in the Women's Health Initiative HT trials (estrogen plus progestin therapy [EPT] and estrogen therapy [ET]). There were 359 incident cases of CHD during follow-up. After the exclusion of women with cardiovascular disease (n = 90), diabetes, or hypertension at baseline (n = 103), 166 CHD cases were matched to 524 controls on age, randomization date, and hysterectomy status. MetS classification required at least three of five Adult Treatment Panel III criteria. Analyses by χ and t tests for heterogeneity and logistic regression were performed. Postmenopausal women (n = 27,347) aged 50 to 79 years from 40 US clinical centers participated. Daily conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg; EPT) or conjugated equine estrogens (0.625 mg; ET) were compared with placebo. The main outcome measure was the odds for CHD with HT use versus placebo by MetS status.MetS modified the risk of CHD events with HT. In the pooled analysis, risk was increased with HT versus placebo in women with MetS (odds ratio, 2.26; 95% CI, 1.26-4.07), whereas women without MetS were not found to have an increased risk for a CHD event with HT (odds ratio, 0.97; 95% CI, 0.58-1.61; P for interaction = 0.03). Results of the EPT and ET trials, when examined separately, were similar. The constellation of MetS variables was more predictive of risk from HT than MetS components assessed individually. When women with diabetes or hypertension were included in the analysis, statistically significant effect modification was not detected.MetS at baseline in women without prior cardiovascular disease, diabetes, or hypertension at baseline identifies women who are more likely to have had adverse coronary outcomes on HT. CHD risk stratification is recommended before initiating HT. The basis for the greater risk of CHD events with HT among women with MetS requires further study.

  View details for DOI 10.1097/gme.0b013e31826f80e0

  View details for Web of Science ID 000315603200006

  View details for PubMedID 23435021

• Geriatric Syndromes and Incident Disability in Older Women: Results from the Women's Health Initiative Observational Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Rosso, A. L., Eaton, C. B., Wallace, R., Gold, R., Stefanick, M. L., Ockene, J. K., Curb, J. D., Michael, Y. L. 2013; 61 (3): 371-379

  Abstract

  To determine how the number of geriatric syndromes is associated with incident disability in community-based populations of older adults.Longitudinal analysis from the Women's Health Initiative Observational Study (WHI-OS).Community.Twenty-nine thousand five hundred forty-four women aged 65 and older enrolled in the WHI-OS and free of disability in activities of daily living (ADLs) at baseline.Geriatric syndromes (high depressive symptoms, dizziness, falls, hearing or visual impairment, osteoporosis, polypharmacy, syncope, sleep disturbance, and urinary incontinence) were self-reported at baseline and 3-year follow-up. Disability was defined as dependence in any ADL and was assessed at baseline and follow-up. Chronic diseases were measured according to a modified Charlson Index.Geriatric syndromes were common in this population of women; 76.3% had at least one syndrome at baseline. Greater number of geriatric syndromes at baseline was significantly associated with greater risk of incident ADL disability at follow-up (P ≤ .001). Adjusted risk ratios were 1.21 (95% confidence interval (CI) = 0.78-1.87) for a single syndrome and 6.64 (95% CI = 4.15-10.62) for five or more syndromes compared with no syndromes. These results were only slightly attenuated after adjustment for number of chronic diseases or pain.Geriatric syndromes are significantly associated with onset of disability in older women; this association is not simply a result of chronic disease or pain. A better understanding of how these conditions contribute to disablement is needed. Geriatric syndrome assessment should be considered along with chronic disease management in the prevention of disability in older women.

  View details for DOI 10.1111/jgs.12147

  View details for Web of Science ID 000316334900008

  View details for PubMedID 23452034

• Self-Reported Snoring and Risk of Cardiovascular Disease Among Postmenopausal Women (from the Women's Health Initiative) AMERICAN JOURNAL OF CARDIOLOGY Sands, M., Loucks, E. B., Lu, B., Carskadon, M. A., Sharkey, K., Stefanick, M., Ockene, J., Shah, N., Hairston, K. G., Robinson, J., Limacher, M., Hale, L., Eaton, C. B. 2013; 111 (4): 540-546

  Abstract

  Habitual snoring may be associated with cardiovascular disease (CVD); however, limited evidence exists among women. We investigated whether frequent snoring is a predictor of coronary heart disease (CHD) and stroke among 42,244 postmenopausal women participating in the Women's Health Initiative Observational Study. Participants provided self-reported information regarding snoring habits at baseline (1993 to 1998) and were followed up for outcomes through August 2009. Physician adjudicators confirmed CHD (defined as myocardial infarction, CHD death, revascularization procedures, or hospitalized angina) and ischemic stroke. Cox proportional hazards models were used to evaluate whether snoring frequency is a significant predictor of the adjudicated outcomes. We observed 2,401 incident cases of CHD during 437,899 person-years of follow-up. After adjusting for age and race, frequent snoring was associated with incident CHD (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.39 to 1.70) and stroke (HR 1.41, 95% CI 1.19 to 1.66), and all CVD (HR 1.46, 95% CI 1.34 to 1.60). In fully adjusted models that included CVD risk factors such as obesity, hypertension, and diabetes, frequent snoring was associated with a more modest increase in incident CHD (HR 1.14, 95% CI 1.01 to 1.28), stroke (HR 1.19, 95% CI 1.02 to 1.40), and CVD (HR 1.12, 95% CI 1.01 to 1.24). In conclusion, snoring is associated with a modest increased risk of incident CHD, stroke, and CVD after adjustment for CVD risk factors. Additional studies are needed to elucidate the mechanisms by which snoring might be associated with CVD risk factors and outcomes.

  View details for DOI 10.1016/j.amjcard.2012.10.039

  View details for Web of Science ID 000315322800014

  View details for PubMedID 23219175

• Body mass index, physical activity, and survival after endometrial cancer diagnosis: Results from the Women's Health Initiative GYNECOLOGIC ONCOLOGY Arem, H., Chlebowski, R., Stefanick, M. L., Anderson, G., Wactawski-Wende, J., Sims, S., Gunter, M. J., Irwin, M. L. 2013; 128 (2): 181-186

  Abstract

  While low physical activity and high body mass index (BMI) have been associated with higher endometrial cancer incidence, no previous studies have evaluated the association between physical activity and survival after endometrial cancer diagnosis, and studies on BMI and survival have not been performed in a prospective cohort.We examined pre-diagnosis BMI and moderate- to vigorous-intensity physical activity in relation to overall and disease-specific survival among 983 postmenopausal women who were diagnosed with endometrial cancer in the Women's Health Initiative Observational Study and Clinical Trials.Over a median 5.2 (max 14.1) years from diagnosis to death or end of follow-up, 163 total deaths were observed, 66 of which were due to endometrial cancer. We observed a higher all-cause mortality hazard ratio (HR) = 1.85 (95% CI 1.19-2.88) comparing women with a BMI ≥ 35 kg/m(2) to women with BMI< 25 kg/m(2). For endometrial cancer-specific mortality the HR = 2.23 (95% CI 1.09-4.54) comparing extreme BMI categories. To examine histologic subtypes we analyzed type I endometrial tumors separately and found an HR = 1.20 (95% CI 1.07-1.35) associated with all-cause mortality for each 5-unit change in BMI. Moderate- to vigorous-intensity physical activity was not associated with all-cause or endometrial cancer-specific mortality.Pre-diagnosis BMI, but not physical activity, was associated with survival among women with endometrial cancer. Future studies should investigate mechanisms and timing of BMI onset to better understand the burden of disease attributable to BMI.

  View details for DOI 10.1016/j.ygyno.2012.10.029

  View details for Web of Science ID 000314445300007

  View details for PubMedID 23127972

• Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women. BMC public health Saquib, N., Brunner, R., Kubo, J., Tindle, H., Kroenke, C., Desai, M., Daviglus, M. L., Allen, N., Martin, L. W., Robinson, J., Stefanick, M. L. 2013; 13: 468-?

  Abstract

  BACKGROUND: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death. METHODS: Postmenopausal women (aged 50--79 years) in control groups of the Women's Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993--2005). RESULTS: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death. CONCLUSION: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death.

  View details for DOI 10.1186/1471-2458-13-468

  View details for PubMedID 23672763

• EDUCATIONAL ATTAINMENT, MRI CHANGES, AND COGNITIVE FUNCTION IN OLDER POSTMENOPAUSAL WOMEN FROM THE WOMEN'S HEALTH INITIATIVE MEMORY STUDY INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE Rapp, S. R., Espeland, M. A., Manson, J. E., Resnick, S. M., Bryan, N. R., Smoller, S., Coker, L. H., Phillips, L. S., Stefanick, M. L., Sarto, G. E. 2013; 46 (2): 121-143

  View details for DOI 10.2190/PM.46.2.a

  View details for Web of Science ID 000329035200001

• Demographic and health factors associated with enrollment in posttrial studies: The women's health initiative hormone therapy trials. Clinical trials Espeland, M. A., Pettinger, M., Falkner, K. L., Shumaker, S. A., Limacher, M., Thomas, F., Weaver, K. E., Stefanick, M. L., McQuellon, C., Hunt, J. R., Johnson, K. C. 2013; 10 (3): 463-472

  Abstract

  After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied.We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials.We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees.The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76).We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols.Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.

  View details for DOI 10.1177/1740774513477931

  View details for PubMedID 23480899

• Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation The Women's Health Initiative Randomized Controlled Trials CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. L. 2012; 5 (6): 1108-1116

  Abstract

  Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.ClinicalTrials.gov; Identifier: NCT00000611.

  View details for DOI 10.1161/CIRCEP.112.972224

  View details for Web of Science ID 000313586900018

  View details for PubMedID 23169946

• The Association of Concurrent Vitamin D and Sex Hormone Deficiency With Bone Loss and Fracture Risk in Older Men: The Osteoporotic Fractures in Men (MrOS) Study JOURNAL OF BONE AND MINERAL RESEARCH Barrett-Connor, E., Laughlin, G. A., Li, H., Nielson, C. M., Wang, P. Y., Dam, T. T., Cauley, J. A., Ensrud, K. E., Stefanick, M. L., Lau, E., Hoffman, A. R., Orwoll, E. S. 2012; 27 (11): 2306-2313

  Abstract

  Low 25-hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case-cohort design. "Abnormal" was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate-adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6-year median follow-up was 1.2 (0.8-1.8) for low VitD alone; 1.3 (0.9-1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1-2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health.

  View details for DOI 10.1002/jbmr.1697

  View details for Web of Science ID 000313729500011

  View details for PubMedID 22777902

• Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls AGE AND AGEING Karlsson, M. K., Ribom, E., Nilsson, J., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Mallmin, H., Stefanick, M., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Rosengren, B. E. 2012; 41 (6): 740-746

  Abstract

  recurrent fallers are at especially high risk for injuries.to study whether tests of physical performance are associated with recurrent falls.a total of 10,998 men aged 65 years or above.questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference.in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall.low performance in physical ability tests are in elderly men associated with recurrent falls.

  View details for DOI 10.1093/ageing/afs104

  View details for Web of Science ID 000310153100009

  View details for PubMedID 22923607

• A low-fat dietary pattern and risk of metabolic syndrome in postmenopausal women: The Women's Health Initiative METABOLISM-CLINICAL AND EXPERIMENTAL Neuhouser, M. L., Howard, B., Lu, J., Tinker, L. F., Van Horn, L., Caan, B., Rohan, T., Stefanick, M. L., Thomson, C. A. 2012; 61 (11): 1572-1581

  Abstract

  Nutrition plays an important role in metabolic syndrome etiology. We examined whether the Women's Health Initiative (WHI) Dietary Modification Trial influenced metabolic syndrome risk.48,835 postmenopausal women aged 50-79 years were randomized to a low-fat (20% energy from fat) diet (intervention) or usual diet (comparison) for a mean of 8.1 years. Blood pressure, waist circumference and fasting blood measures of glucose, HDL-cholesterol and triglycerides were measured on a subsample (n=2816) at baseline and years 1, 3 and 6 post-randomization. Logistic regression estimated associations of the intervention with metabolic syndrome risk and use of cholesterol-lowering and hypertension medications. Multivariate linear regression tested associations between the intervention and metabolic syndrome components.At year 3, but not years 1 or 6, women in the intervention group (vs. comparison) had a non-statistically significant lower risk of metabolic syndrome (OR=0.83, 95%CI 0.59-1.18). Linear regression models simultaneously modeling the five metabolic syndrome components revealed significant associations of the intervention with metabolic syndrome at year 1 (p<0.0001), but not years 3 (p=0.19) and 6 (p=0.17). Analyses restricted to intervention-adherent participants strengthened associations at years 3 (p=0.05) and 6 (p=0.06). Cholesterol-lowering and hypertension medication use was 19% lower at year 1 for intervention vs. comparison group women (OR=0.81, 95% CI 0.60-1.09).Over the entire trial, fewer intervention vs. comparison participants used these medications (26.0% vs. 29.9%), although results were not statistically significant (p=0.89).The WHI low-fat diet may influence metabolic syndrome risk and decrease use of hypertension and cholesterol-lowering medications. Findings have potential for meaningful clinical translation.

  View details for DOI 10.1016/j.metabol.2012.04.007

  View details for Web of Science ID 000310557900010

  View details for PubMedID 22633601

• Determinants of Racial/Ethnic Disparities in Incidence of Diabetes in Postmenopausal Women in the U.S. The Women's Health Initiative 1993-2009 DIABETES CARE Ma, Y., Hebert, J. R., Manson, J. E., Balasubramanian, R., Liu, S., LaMonte, M. J., Bird, C. E., Ockene, J. K., Qiao, Y., Olendzki, B., Schneider, K. L., Rosal, M. C., Sepavich, D. M., Wactawski-Wende, J., Stefanick, M. L., Phillips, L. S., Ockene, I. S., Kaplan, R. C., Sarto, G. E., Garcia, L., Howard, B. V. 2012; 35 (11): 2226-2234

  Abstract

  To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women's Health Initiative.Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993-1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47-1.63), 1.67 for Hispanics (1.54-1.81), and 1.86 for Asians (1.68-2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.

  View details for DOI 10.2337/dc12-0412

  View details for Web of Science ID 000311424100024

  View details for PubMedID 22833490

• A Prospective Study of Leukocyte Telomere Length and Risk of Type 2 Diabetes in Postmenopausal Women DIABETES You, N. Y., Chen, B. H., Song, Y., Lu, X., Chen, Y., Manson, J. E., Kang, M., Howard, B. V., Margolis, K. L., Curb, J. D., Phillips, L. S., Stefanick, M. L., Tinker, L. F., Liu, S. 2012; 61 (11): 2998-3004

  Abstract

  Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women's Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90-1.11) in whites, 0.95 (0.85-1.06) in blacks, 0.96 (0.79-1.17) in Hispanics, and 0.88 (0.70-1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.

  View details for DOI 10.2337/db12-0241

  View details for Web of Science ID 000312041600039

  View details for PubMedID 22829448

• Change in hip bone mineral density and risk of subsequent fractures in older men JOURNAL OF BONE AND MINERAL RESEARCH Cawthon, P. M., Ewing, S. K., Mackey, D. C., Fink, H. A., Cummings, S. R., Ensrud, K. E., Stefanick, M. L., Bauer, D. C., Cauley, J. A., Orwoll, E. S. 2012; 27 (10): 2179-2188

  Abstract

  Low bone mineral density (BMD) increases fracture risk; how changes in BMD influence fracture risk in older men is uncertain. BMD was assessed at two to three time points over 4.6 years using dual-energy X-ray absorptiometry (DXA) for 4470 men aged ≥65 years in the Osteoporotic Fractures in Men (MrOS) Study. Change in femoral neck BMD was estimated using mixed effects linear regression models. BMD change was categorized as "accelerated" (≤-0.034 g/cm(2) ), "expected" (between 0 and -0.034 g/cm(2) ), or "maintained" (≥0 g/cm(2) ). Fractures were adjudicated by central medical record review. Multivariate proportional hazards models estimated the risk of hip, nonspine/nonhip, and nonspine fracture over 4.5 years after the final BMD measure, during which time 371 (8.3%) men experienced at least one nonspine fracture, including 78 (1.7%) hip fractures. Men with accelerated femoral neck BMD loss had an increased risk of nonspine (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.4-2.8); nonspine/nonhip (HR = 1.6; 95% CI 1.1-2.3); and hip fracture (HR = 6.3; 95% CI 2.7-14.8) compared with men who maintained BMD over time. No difference in risk was seen for men with expected loss. Adjustment for the initial BMD measure did not alter the results. Adjustment for the final BMD measure attenuated the change in BMD-nonspine fracture and the change in BMD-nonspine/nonhip relationships such that they were no longer significant, whereas the change in the BMD-hip fracture relationship was attenuated (HR = 2.6; 95% CI 1.1-6.4). Total hip BMD change produced similar results. Accelerated decrease in BMD is a strong, independent risk factor for hip and other nonspine fractures in men.

  View details for DOI 10.1002/jbmr.1671

  View details for Web of Science ID 000308925800015

  View details for PubMedID 22648990

• Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Kroenke, C. H., Caan, B. J., Stefanick, M. L., Anderson, G., Brzyski, R., Johnson, K. C., Leblanc, E., Lee, C., La Croix, A. Z., Park, H. L., Sims, S. T., Vitolins, M., Wallace, R. 2012; 19 (9): 980-988

  Abstract

  The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women.We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women's Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations.In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (≥ 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS.Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.

  View details for DOI 10.1097/gme.0b013e31824f606e

  View details for Web of Science ID 000308415500008

  View details for PubMedID 22781782

  View details for PubMedCentralID PMC3428489

• Alcohol consumption and body weight change in postmenopausal women: results from the Women's Health Initiative INTERNATIONAL JOURNAL OF OBESITY Thomson, C. A., Wertheim, B. C., Hingle, M., Wang, L., Neuhouser, M. L., Gong, Z., Garcia, L., Stefanick, M. L., Manson, J. E. 2012; 36 (9): 1158-1164

  Abstract

  To determine whether alcohol consumption is associated with incident overweight or obesity in normal-weight, postmenopausal women.Prospective cohort study considering baseline alcohol consumption and subsequent weight change over 7 years.15,920 normal-weight (body mass index (BMI): 18.5 to <25 kg m(-2)), postmenopausal women enrolled in the Women's Health Initiative Clinical Trial.Body weight change, and incident overweight and obesity (BMI, 25.0 to <30 and ≥ 30 kg m(-2)) over 7 years.One-third of the 13,822 women included in the analytical cohort reported no alcohol consumption. BMI differed little between abstainers (22.8±1.58 kg m(-2)) and alcohol consumers in the upper quintile (22.7±1.53 kg m(-2)). Among normal-weight women, the risk of becoming overweight or obese over a 7-year follow-up period was 35% or 88% lower, respectively, for women in the upper quintile of alcohol intake relative to abstainers (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.58-0.73; or HR, 0.12; 95% CI, 0.05-0.25, respectively). Risk for overweight and obesity was not significantly modified by age. Wine consumption showed the greatest protective association for risk of overweight (HR, 0.75; 95% CI, 0.68-0.84), followed by liquor (HR, 0.85; 95% CI, 0.78-0.93) and beer (HR, 0.90; 95% CI, 0.82-1.00).Postmenopausal women of normal weight who report moderate alcohol intake have a reduced risk of becoming overweight or obese over time. Perhaps, weight control measures in this population should target behaviors other than reduction in alcohol for those of normal BMI consuming moderate amounts.

  View details for DOI 10.1038/ijo.2012.84

  View details for Web of Science ID 000308631400004

  View details for PubMedID 22689071

• A longitudinal study of the metabolic syndrome and risk of colorectal cancer in postmenopausal women EUROPEAN JOURNAL OF CANCER PREVENTION Kabat, G. C., Kim, M. Y., Peters, U., Stefanick, M., Hou, L., Wactawski-Wende, J., Messina, C., Shikany, J. M., Rohan, T. E. 2012; 21 (4): 326-332

  Abstract

  The metabolic syndrome is associated with increased risk of diabetes and coronary heart disease. Although higher BMI and other related factors have been frequently associated with colorectal cancer, whether the metabolic syndrome is associated with the risk of colorectal cancer is unclear. We therefore assessed the association of the metabolic syndrome with the risk of colorectal cancer in a subsample of participants of the Women's Health Initiative who had repeated measurements of the components of the syndrome at baseline and during follow-up. Women with diabetes at baseline enrollment were excluded. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) at baseline and in time-dependent analyses. Among 4862 eligible women, 81 incident cases of colorectal cancer were identified over a median follow-up of 12 years. Presence of the metabolic syndrome at baseline was associated with increased risk of colorectal cancer (HR 2.15, 95% CI 1.30-3.53) and colon cancer (HR 2.28, 95% CI 1.31-3.98). These associations were largely explained by positive associations of serum glucose and systolic blood pressure with both outcomes. Time-dependent covariate analyses supported the baseline findings. Our results suggest that the positive association of the metabolic syndrome with risk of colorectal cancer is largely accounted for by serum glucose levels and systolic blood pressure. The biological mechanism underlying these associations remains to be clarified.

  View details for DOI 10.1097/CEJ.0b013e32834dbc81

  View details for Web of Science ID 000304528400003

  View details for PubMedID 22044849

• The 2010 North American Menopause Society position statement on hormone therapy goes beyond the available evidence MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Anderson, G., LaCroix, A., Limacher, M., Prentice, R., Stefanick, M., Wassertheil-Smoller, S., Rossouw, J. 2012; 19 (7): 835-836

  View details for DOI 10.1097/gme.0b013e3182594f76

  View details for Web of Science ID 000305900100019

  View details for PubMedID 22668818

• Physical Activity and Inflammation in a Multiethnic Cohort of Women MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Lee, I., Sesso, H. D., Ridker, P. M., Mouton, C. P., Stefanick, M. L., Manson, J. E. 2012; 44 (6): 1088-1096

  Abstract

  Many cross-sectional studies using data from a single time point have reported that higher levels of physical activity or fitness are associated with lower levels of inflammatory markers, but data examining change are limited, as are race/ethnicity-specific data. The purpose of this study was to examine the associations between physical activity and inflammation assessed at two time points among women of different race/ethnicities.A total of 1355 postmenopausal women (301 whites, 300 blacks, 300 Hispanics, 300 Asians/Pacific Islanders, and 154 American Indians) age 50-79 yr were studied. Participants were from 40 US cities and were free of cardiovascular disease and cancer. At baseline and year 3, women reported their recreational physical activities and provided blood samples, which were analyzed for several inflammatory markers.In cross-sectional analyses, after adjusting for several potential confounders including body mass index, higher physical activity levels were generally related to lower inflammatory marker concentrations. For example, P values for a linear trend of lower C-reactive protein levels across physical activity tertiles at baseline were <0.0001 in all women and 0.94, 0.09, 0.002, 0.20, and 0.10, respectively, for the five race/ethnic groups listed above. For interleukin 6, the corresponding P values were <0.0001, 0.0007, 0.01, 0.03, 0.37, and 0.004, respectively, at baseline. Relationships at year 3 were similar to baseline. However, there was no relation between changes in physical activity and changes in inflammatory markers during the 3-yr period.Among middle-age and older women overall, there were strong, inverse, cross-sectional associations between physical activity level and inflammatory markers. However, changes in inflammatory markers were unrelated to changes in physical activity. These data suggest a noncausal association between physical activity and inflammatory markers.

  View details for DOI 10.1249/MSS.0b013e318242b11a

  View details for Web of Science ID 000304227100015

  View details for PubMedID 22595984

• Estrogen plus progestin (E plus P) and breast cancer incidence and mortality 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Chlebowski, R. T., Anderson, G. L., Kuller, L. H., Aragaki, A. K., Manson, J. E., Stefanick, M. L., Johnson, K., Gass, M., Lane, D. S., Ockene, J., Sarto, G., Wactawski-Wende, J., Rajkovic, A., Prentice, R. L. AMER SOC CLINICAL ONCOLOGY. 2012

  View details for Web of Science ID 000318009801330

• Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk AGE AND AGEING Rosengren, B. E., Ribom, E. L., Nilsson, J., Mallmin, H., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Stefanick, M., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Karlsson, M. K. 2012; 41 (3): 339-344

  Abstract

  most fractures are preceded by falls.the aim of this study was to determine whether tests of physical performance are associated with fractures. Subjects: a total of 10,998 men aged 65 years or above were recruited.questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference.fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture.the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers.

  View details for DOI 10.1093/ageing/afs010

  View details for Web of Science ID 000303335000011

  View details for PubMedID 22314696

• EFFECTS OF POSTMENOPAUSAL HORMONE THERAPY ON INCIDENT ATRIAL FIBRILLATION: THE WOMEN'S HEALTH INITIATIVE RANDOMIZED CONTROLLED TRIALS 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Perez, M. V., Wang, P., Larson, J., Virnig, B. A., Cochrane, B., Curb, D., Klein, L., Manson, J., Martin, L., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. ELSEVIER SCIENCE INC. 2012: E661–E661

  View details for Web of Science ID 000302326700663

• Physical Activity and Body Mass: Changes in Younger versus Older Postmenopausal Women MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Sims, S. T., Larson, J. C., LaMonte, M. J., Michael, Y. L., Martin, L. W., Johnson, K. C., Sarto, G. E., Stefanick, M. L. 2012; 44 (1): 89-97

  Abstract

  The study's purpose was to investigate the relationship of sedentary (≤ 100 MET · min · wk(-1)), low (>100-500 MET · min · wk(-1)), moderate (>500-1200 MET · min · wk(-1)), and high (>1200 MET · min · wk(-1)) habitual physical activity with body weight, body mass index, and measures of fat distribution (waist-to-hip ratio) in postmenopausal women by age decades.A prospective cohort study of 58,610 postmenopausal women age 50-79 yr weighed annually during 8 yr at one of 40 US clinical centers was analyzed to determine the relationship of high versus low habitual physical activity with changes in body weight and fat distribution by age group.Among women age 50-59 yr, there was significant weight loss in those expending >500-1200 MET · min · wk(-1) (coefficient = -0.30, 95% confidence interval = -0.53 to -0.07) compared with the group expending ≤ 100 MET · min · wk(-1). Among women age 70-79 yr, higher physical activity was associated with less weight loss (coefficient = 0.34, 95% confidence interval = 0.04-0.63). Age at baseline significantly modified the association between physical activity and total weight change, whereas baseline body mass index did not.High habitual physical activity is associated with less weight gain in younger postmenopausal women and less weight loss in older postmenopausal women. These findings suggest that promoting physical activity among postmenopausal women may be important for managing body weight changes that accompany aging.

  View details for DOI 10.1249/MSS.0b013e318227f906

  View details for Web of Science ID 000298377400012

  View details for PubMedID 21659897

• SELF-REPORTED SNORING AND CARDIOVASCULAR OUTCOMES AMONG POSTMENOPAUSAL WOMEN: THE WOMEN'S HEALTH INITIATIVE (WHI) 26th Annual Meeting of the Association-of-Professional-Sleep-Societies (APSS) Sands, M., Loucks, E. B., Lu, B., Stefanick, M. L., Ockene, J. K., Shah, N., Hairston, K. G., Limacher, M., Hale, L., Eaton, C. B. AMER ACAD SLEEP MEDICINE. 2012: A410–A410

  View details for Web of Science ID 000312996502457

• Associations Between Sleep Architecture and Sleep-Disordered Breathing and Cognition in Older Community-Dwelling Men: The Osteoporotic Fractures in Men Sleep Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Blackwell, T., Yaffe, K., Ancoli-Israel, S., Redline, S., Ensrud, K. E., Stefanick, M. L., Laffan, A., Stone, K. L. 2011; 59 (12): 2217-2225

  Abstract

  To examine the association between sleep architecture, sleep-disordered breathing, and cognition in older men.Population-based cross-sectional study.Six clinical sites in the United States.Two thousand nine hundred nine community-dwelling men aged 67 and older who were not selected on the basis of sleep problems or cognitive impairment.Predictors were measured using in-home polysomnography: sleep architecture, nocturnal hypoxemia (any sleep time with arterial oxygen saturation <80%), apnea-hypopnea index (AHI), and arousal index. Cognitive outcomes were measured using the modified Mini-Mental State Examination (3MS), Trail-Making Test Part B (TMT-B), and the Digit Vigilance Test (DVT).Analyses adjusted for age, race, education, body mass index, lifestyle, comorbidities, and medication use showed that participants who spent less percentage of time in rapid eye movement (REM) sleep had lower levels of cognition; participants in the lowest quartile (<14.8%) took an average of 5.9 seconds longer on the TMT-B and 20.1 seconds longer on the DVT than those in the highest quartile (≥23.7%). Similarly, greater percentage of time spent in Stage 1 sleep was related to poorer cognitive function. Participants in the highest quartile of Stage 1 sleep (≥8.6%) had worse cognitive scores on average than those in the lowest quartile (<4.0%). Those with nocturnal hypoxemia took an average of 22.3 seconds longer to complete the DVT than those without, but no associations were found with 3MS or the TMT-B.Spending less percentage of time in REM sleep and greater percentage of time in Stage 1 sleep and having higher levels of nocturnal hypoxemia were associated with poorer cognition in older men. Further studies are needed to clarify the direction of these associations and to explore potential mechanisms.

  View details for DOI 10.1111/j.1532-5415.2011.03731.x

  View details for Web of Science ID 000298600300004

  View details for PubMedID 22188071

• There is in elderly men a group difference between fallers and non-fallers in physical performance tests AGE AND AGEING Rosengren, B., Ribom, E. L., Nilsson, J., Ljunggren, O., Ohlsson, C., Mellstrom, D., Lorentzon, M., Mallmin, H., Stefanick, M. L., Lapidus, J., Leung, P. C., Kwok, A., Barrett-Connor, E., Orwoll, E., Karlsson, M. K. 2011; 40 (6): 744-749

  View details for DOI 10.1093/ageing/afr108

  View details for Web of Science ID 000296095300019

  View details for PubMedID 21914663

• Interaction Between Smoking and Obesity and the Risk of Developing Breast Cancer Among Postmenopausal Women AMERICAN JOURNAL OF EPIDEMIOLOGY Luo, J., Horn, K., Ockene, J. K., Simon, M. S., Stefanick, M. L., Tong, E., Margolis, K. L. 2011; 174 (8): 919-928

  Abstract

  Obesity is a well-established risk factor for postmenopausal breast cancer. Recent studies suggest that smoking increases the risk of breast cancer. However, the effect of co-occurrence of smoking and obesity on breast cancer risk remains unclear. A total of 76,628 women aged 50-79 years enrolled in the Women's Health Initiative Observational Study were followed through August 14, 2009. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. Over an average 10.3 years of follow-up, 3,378 incident cases of invasive breast cancer were identified. The effect of smoking on the risk of developing invasive breast cancer was modified significantly by obesity status among postmenopausal women, regardless of whether the obesity status was defined by body mass index (P(interaction) = 0.01) or waist circumference (P(interaction) = 0.02). A significant association between smoking and breast cancer risk was noted in nonobese women (hazard ratio = 1.25, 95% confidence interval: 1.05, 1.47) but not in obese women (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). In conclusion, this study suggests that the effect of smoking exposure on breast cancer risk was modified by obesity among postmenopausal women. The modification effect did not differ by general versus abdominal obesity.

  View details for DOI 10.1093/aje/kwr192

  View details for Web of Science ID 000295679700006

  View details for PubMedID 21878422

• Menopausal Hormone Therapy and Risks of Melanoma and Nonmelanoma Skin Cancers: Women's Health Initiative Randomized Trials JOURNAL OF THE NATIONAL CANCER INSTITUTE Tang, J. Y., Spaunhurst, K. M., Chlebowski, R. T., Wactawski-Wende, J., Keiser, E., Thomas, F., Anderson, M. L., Zeitouni, N. C., Larson, J. C., Stefanick, M. L. 2011; 103 (19): 1469-1475

  Abstract

  Case-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer. The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women's Health Initiative randomized placebo-controlled hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen only (E-alone).Postmenopausal women aged 50-79 years were randomly assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1 years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone trial]) were ascertained by self-report. Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records. Incidences of nonmelanoma skin cancer and melanoma were compared between the two randomization groups within each trial using hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) and Wald statistic P values from Cox proportional hazards models. All statistical tests were two-sided.Rates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to 1.37). Results were similar for the E + P and E-alone trials when analyzed individually.Menopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma. These findings do not support a role of menopausal estrogen, with or without progestin, in the development of skin cancer in postmenopausal women.

  View details for DOI 10.1093/jnci/djr333

  View details for Web of Science ID 000295683800011

  View details for PubMedID 21878677

  View details for PubMedCentralID PMC3186783

• Reproductive and menstrual factors and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women CANCER CAUSES & CONTROL Kabat, G. C., Kim, M. Y., Woods, N. F., Habel, L. A., Messina, C. R., Wactawski-Wende, J., Stefanick, M. L., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2011; 22 (10): 1415-1424

  Abstract

  The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood.The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women's Health Initiative (WHI) clinical trial participants, in which mammography was protocol mandated. The cohort consisted of 64,060 women, among whom 664 cases of DCIS were ascertained over a median follow-up of 12.0 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).After adjustment for covariates, only older age at menopause (HR ≥ 55 vs. 45-54 : 1.39, 95% CI 1.08-1.79) was significantly associated with risk; however, greater parity (HR ≥ 5 live births vs. 0: 0.70, 95% CI 0.47-1.03), among parous women, and age at first live birth (HR ≥ 30 years relative to <20 years: 1.32, 95% CI 0.92-1.90) were of borderline significance. Age at menarche and months of breast-feeding were not associated with risk. Associations did not differ between high- and low-/moderate-grade DCIS, or by level of body mass index or family history of breast cancer; however, there was a suggestion that the associations of age at menopause, parity, and age at first live birth were limited to women who had ever used hormone therapy.Findings from this large cohort of postmenopausal women suggest that age at menopause, and possibly, age at first live birth, and parity are associated with risk of DCIS, whereas age at menarche and duration of breast-feeding are not.

  View details for DOI 10.1007/s10552-011-9814-8

  View details for Web of Science ID 000295992000007

  View details for PubMedID 21750889

• Association of Sleep Characteristics and Cognition in Older Community-Dwelling Men: the MrOS Sleep Study SLEEP Blackwell, T., Yaffe, K., Ancoli-Israel, S., Redline, S., Ensrud, K. E., Stefanick, M. L., Laffan, A., Stone, K. L. 2011; 34 (10): 1347-1356

  Abstract

  To examine the association of objectively and subjectively measured sleep characteristics with cognition in older men.A population-based cross-sectional study.6 centers in the United States.3,132 community-dwelling older men (mean age 76.4 ± 5.6 years).None.Objectively measured sleep predictors from wrist actigraphy were total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self-reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive outcomes were measured with the Modified Mini-Mental State examination (3MS), the Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple potential confounders, WASO was modestly related to poorer cognition. Compared to those with WASO < 90 min, men with WASO ≥ 90 min took 6.1 sec longer to complete the Trails B test and had a 0.9-point worse 3MS score, on average (P<0.05). Actigraphically measured long sleepers had a slightly worse 3MS score compared to those with 7-8 h of sleep, but had similar Trails B and DVT completion times. Compared to those who self-reported sleeping 7-8 h, long sleepers (>8 h) on average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse 3MS score, and took 46 sec longer to complete the DVT (P<0.05). PSQI and EDS were not independently related to cognitive outcomes.There were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. EDS and PSQI were not related to cognition.

  View details for DOI 10.5665/SLEEP.1276

  View details for Web of Science ID 000295624800011

  View details for PubMedID 21966066

  View details for PubMedCentralID PMC3174836

• Association of Incident Cardiovascular Disease With Periodic Limb Movements During Sleep in Older Men Outcomes of Sleep Disorders in Older Men (MrOS) Study CIRCULATION Koo, B. B., Blackwell, T., Ancoli-Israel, S., Stone, K. L., Stefanick, M. L., Redline, S. 2011; 124 (11): 1223-1231

  Abstract

  Periodic limb movements during sleep (PLMS) cause repetitive sympathetic activation and may be associated with increased cardiovascular risk. We hypothesized that PLMS frequency (periodic limb movement index [PLMI]) and PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are predictive of incident cardiovascular disease, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease, in an elderly male cohort.A total of 2911 men in the observational Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study cohort underwent in-home polysomnography with PLMS measurement and were followed up for 4 years for the outcomes coronary heart disease, cerebrovascular disease, peripheral arterial disease, and all-cause cardiovascular disease, which included coronary heart disease, cerebrovascular disease, and peripheral arterial disease. Cox proportional hazards regression assessed the association between PLMI, PLMAI, and these outcomes. Models were minimally adjusted for age, clinic, and body mass index and then fully adjusted for conventional cardiovascular risk factors. During follow-up, 500 men experienced all-cause cardiovascular disease: 345 coronary heart disease, 117 cerebrovascular disease, and 98 peripheral arterial disease events. In fully adjusted models, men with PLMAI ≥5 compared with the referent PLMA <1 group had a 1.26-fold increased relative hazard for all-cause cardiovascular disease. Similar findings were observed for PLMI and all-cause cardiovascular disease. For peripheral arterial disease, men with PLMI ≥30 compared with the referent PLMI <5 group had a 2-fold increased relative hazard (95% confidence interval, 1.14 to 3.49; P=0.025). Compared with the referent group, men with PLMI ≥30 had an increased risk of coronary heart disease (relative hazard, 1.31; 95% confidence interval, 1.01 to 1.70; P=0.045) after minimal adjustment, but this association was attenuated after further adjustments. After stratification, risk of incident all-cause cardiovascular disease among high-PLMI and high-PLMAI groups was significantly elevated only for men without prevalent hypertension (P for interactions <0.10).These findings provide evidence that PLMS frequency is associated with incident cardiovascular disease in community-dwelling elderly men.

  View details for DOI 10.1161/CIRCULATIONAHA.111.038968

  View details for Web of Science ID 000294779000016

  View details for PubMedID 21859975

  View details for PubMedCentralID PMC3265562

• Metabolic Syndrome and Physical Performance in Elderly Men: The Osteoporotic Fractures in Men Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Everson-Rose, S. A., Paudel, M., Taylor, B. C., Dam, T., Cawthon, P. M., Leblanc, E., Strotmeyer, E. S., Cauley, J. A., Stefanick, M. L., Barrett-Connor, E., Ensrud, K. E. 2011; 59 (8): 1376-1384

  Abstract

  To examine the association between metabolic syndrome (MetS) and objective measures of physical performance.Cross-sectional analysis of the cohort study, the Osteoporotic Fractures in Men Study.Six clinical sites in the United States.Five thousand four hundred fifty-seven ambulatory men (mean age 73.6 ± 5.9).Physical performance assessed according to grip strength, narrow walk speed, walking speed, and time to complete five repeated chair stands. Individual scores were converted to quintiles (worst=1 to best=5; unable to complete=0) and summed for an overall score (mean 11.6 ± 4.3, range, 1-20). MetS was defined according to World Health Organization criteria that include evidence of glucose dysregulation (insulin resistance, diabetes mellitus, or hyperinsulinemia) and at least two additional characteristics: high blood pressure, low high-density lipoprotein cholesterol, high triglycerides, obesity.More than one-quarter (26.3%) of participants met criteria for MetS. In separate linear regression models, four of five MetS components were related to performance (P<.001); only high blood pressure was unrelated. Men with MetS had a 1.1-point lower performance score (mean 10.8, 95% confidence interval (CI)=10.6-11.0) than men without MetS (mean 11.9, 95% CI=11.8-12.0) (P<.001), adjusting for age, race, education, and site. With further covariate adjustment, this difference was reduced but remained significant (β=-0.78, P<.001). A graded association was observed between number of MetS components (0, 1, 2, or ≥3) and performance (P for trend <.001). Findings were similar excluding men with diabetes mellitus or obese men.Metabolic dysregulation is related to objectively assessed poorer physical performance in relatively healthy older men.

  View details for DOI 10.1111/j.1532-5415.2011.03518.x

  View details for Web of Science ID 000293980600002

  View details for PubMedID 21806561

• Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial JOURNAL OF CLINICAL ONCOLOGY Tang, J. Y., Fu, T., Leblanc, E., Manson, J. E., Feldman, D., Linos, E., Vitolins, M. Z., Zeitouni, N. C., Larson, J., Stefanick, M. L. 2011; 29 (22): 3078-3084

  Abstract

  In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial.Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication.Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC.Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

  View details for DOI 10.1200/JCO.2011.34.5967

  View details for Web of Science ID 000293222200029

  View details for PubMedID 21709199

  View details for PubMedCentralID PMC3157967

• Vasomotor symptoms and cardiovascular events in postmenopausal women MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Szmuilowicz, E. D., Manson, J. E., Rossouw, J. E., Howard, B. V., Margolis, K. L., Greep, N. C., Brzyski, R. G., Stefanick, M. L., O'Sullivan, M. J., Wu, C., Allison, M., Grobbee, D. E., Johnson, K. C., Ockene, J. K., Rodriguez, B. L., Sarto, G. E., Vitolins, M. Z., Seely, E. W. 2011; 18 (6): 603-610

  Abstract

  Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N = 60,027): (1) no VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]), (2) VMS at menopause onset but not at WHI-OS enrollment (early VMS), (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]), and (4) VMS at WHI-OS enrollment but not at menopause onset (late VMS).For women with early VMS (n = 24,753), compared with no VMS (n = 18,799), hazard ratios (95% CIs) in fully adjusted models were as follows: major coronary heart disease (CHD), 0.94 (0.84-1.06); stroke, 0.83 (0.72-0.96); total CVD, 0.89 (0.81-0.97); and all-cause mortality, 0.92 (0.85-0.99). For women with persistent VMS (n = 15,084), there was no significant association with clinical events. For women with late VMS (n = 1,391), compared with no VMS, hazard ratios (95% CIs) were as follows: major CHD, 1.32 (1.01-1.71); stroke, 1.14 (0.82-1.59); total CVD, 1.23 (1.00-1.52); and all-cause mortality, 1.29 (1.08-1.54).Early VMS were not associated with increased CVD risk. Rather, early VMS were associated with decreased risk of stroke, total CVD events, and all-cause mortality. Late VMS were associated with increased CHD risk and all-cause mortality. The predictive value of VMS for clinical CVD events may vary with the onset of VMS at different stages of menopause. Further research examining the mechanisms underlying these associations is needed. Future studies will also be necessary to investigate whether VMS that develop for the first time in the later postmenopausal years represent a pathophysiologic process distinct from the classic perimenopausal VMS.

  View details for DOI 10.1097/gme.0b013e3182014849

  View details for Web of Science ID 000291004400005

  View details for PubMedID 21358352

• Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative GYNECOLOGIC ONCOLOGY Reeves, K. W., Carter, G. C., Rodabough, R. J., Lane, D., Mcneeley, S. G., Stefanick, M. L., Paskett, E. D. 2011; 121 (2): 376-382

  Abstract

  Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.We studied 86937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade.During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade.Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.

  View details for DOI 10.1016/j.ygyno.2011.01.027

  View details for Web of Science ID 000290292100026

  View details for PubMedID 21324514

• Oophorectomy vs Ovarian Conservation With Hysterectomy Cardiovascular Disease, Hip Fracture, and Cancer in the Women's Health Initiative Observational Study ARCHIVES OF INTERNAL MEDICINE Jacoby, V. L., Grady, D., Wactawski-Wende, J., Manson, J. E., Allison, M. A., Kuppermann, M., Sarto, G. E., Robbins, J., Phillips, L., Martin, L. W., O'Sullivan, M. J., Jackson, R., Rodabough, R. J., Stefanick, M. L. 2011; 171 (8): 760-768

  Abstract

  Elective bilateral salpingo-oophorectomy (BSO) is routinely performed with hysterectomy for benign conditions despite conflicting data on long-term outcomes.This is a prospective cohort of 25 448 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study who had a history of hysterectomy and BSO (n = 14 254 [56.0%]) or hysterectomy with ovarian conservation (n = 11 194 [44.0%]) and no family history of ovarian cancer. Multivariable Cox proportional hazards regression models were used to examine the effect of BSO on incident cardiovascular disease, hip fracture, cancer, and death.Current or past use of estrogen and/or progestin was common irrespective of BSO status (78.6% of cohort). In multivariable analyses, BSO was not associated with an increased risk of fatal and nonfatal coronary heart disease (hazard ratio, 1.00 [95% confidence interval, 0.85-1.18]), coronary artery bypass graft/percutaneous transluminal coronary angioplasty (0.95 [0.82-1.10]), stroke (1.04 [0.87-1.24]), total cardiovascular disease (0.99 [0.91-1.09]), hip fracture (0.83 [0.63-1.10]), or death (0.98 [0.87-1.10]). Bilateral salpingo-oophorectomy decreased incident ovarian cancer (0.02% in the BSO group; 0.33% in the ovarian conservation group; number needed to treat, 323) during a mean (SD) follow-up of 7.6 (1.6) years, but there were no significant associations for breast, colorectal, or lung cancer.In this large prospective cohort study, BSO decreased the risk of ovarian cancer compared with hysterectomy and ovarian conservation, but incident ovarian cancer was rare in both groups. Our findings suggest that BSO may not have an adverse effect on cardiovascular health, hip fracture, cancer, or total mortality compared with hysterectomy and ovarian conservation.

  View details for Web of Science ID 000289853300008

  View details for PubMedID 21518944

• Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy A Randomized Controlled Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LaCroix, A. Z., Chlebowski, R. T., Manson, J. E., Aragaki, A. K., Johnson, K. C., Martin, L., Margolis, K. L., Stefanick, M. L., Brzyski, R., Curb, J. D., Howard, B. V., Lewis, C. E., Wactawski-Wende, J. 2011; 305 (13): 1305-1314

  Abstract

  The Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported.To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009.The intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent.The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death.The postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction).Among postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted.clinicaltrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000289162400019

  View details for PubMedID 21467283

• Physical Activity and Survival in Postmenopausal Women with Breast Cancer: Results from the Women's Health Initiative CANCER PREVENTION RESEARCH Irwin, M. L., McTiernan, A., Manson, J. E., Thomson, C. A., Sternfeld, B., Stefanick, M. L., Wactawski-Wende, J., Craft, L., Lane, D., Martin, L. W., Chlebowski, R. 2011; 4 (4): 522-529

  Abstract

  Although studies have shown that physically active breast cancer survivors have lower all-cause mortality, the association between change in physical activity from before to after diagnosis and mortality is not clear. We examined associations among pre- and postdiagnosis physical activity, change in pre- to postdiagnosis physical activity, and all-cause and breast cancer-specific mortality in postmenopausal women. A longitudinal study of 4,643 women diagnosed with invasive breast cancer after entry into the Women's Health Initiative study of postmenopausal women. Physical activity from recreation and walking was determined at baseline (prediagnosis) and after diagnosis (assessed at the 3 or 6 years post-baseline visit). Women participating in 9 MET-h/wk or more (∼ 3 h/wk of fast walking) of physical activity before diagnosis had a lower all-cause mortality (HR = 0.61; 95% CI, 0.44-0.87; P = 0.01) compared with inactive women in multivariable adjusted analyses. Women participating in ≥ 9 or more MET-h/wk of physical activity after diagnosis had lower breast cancer mortality (HR = 0.61; 95% CI, 0.35-0.99; P = 0.049) and lower all-cause mortality (HR = 0.54; 95% CI, 0.38-0.79; P < 0.01). Women who increased or maintained physical activity of 9 or more MET-h/wk after diagnosis had lower all-cause mortality (HR = 0.67; 95% CI, 0.46-0.96) even if they were inactive before diagnosis. High levels of physical activity may improve survival in postmenopausal women with breast cancer, even among those reporting low physical activity prior to diagnosis. Women diagnosed with breast cancer should be encouraged to initiate and maintain a program of physical activity.

  View details for DOI 10.1158/1940-6207.CAPR-10-0295

  View details for Web of Science ID 000289073700008

  View details for PubMedID 21464032

• Trends in menopausal hormone therapy use of US office-based physicians, 2000-2009 MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Tsai, S. A., Stefanick, M. L., Stafford, R. S. 2011; 18 (4): 385-392

  Abstract

  The aim of this study was to evaluate recent trends and the adoption of practice recommendations for menopausal hormone therapy (MHT) use from 2001 to 2009 by formulation, dose, woman's age, and characteristics of physicians reporting MHT visits.The IMS Health (Plymouth Meeting PA) National Disease and Therapeutic Index physician survey data from 2001 to 2009 were analyzed for visits in which MHT use was reported by US office-based physicians. Estimated national volume of visits for which MHT use was reported.MHT use declined each year since 2002. Systemic MHT use fell from 16.3 million (M) visits in 2001 to 6.1 M visits in 2009. Declines were greatest for women 60 years or older (64%) but were also substantial for women younger than 50 years (59%) and women 50 to 59 years old (60%). Women 60 years or older accounted for 37% of MHT use. Lower dose product use increased modestly, from 0.7 M (2001) to 1.3 M (2009), as did vaginal MHT use, from 1.8 M (2001) to 2.4 M (2009). Declines in continuing systemic MHT use (65%) were greater than for newly initiated MHT use (51%). Compared with other physicians, obstetrician/gynecologists changed their practices less, thereby increasing their overall share of total MHT visits from 72% (2001) to 82% (2009).Total MHT use has steadily declined. Increased use of lower dose and vaginal products reflects clinical recommendations. Uptake of these products, however, has been modest, and substantial use of MHT continues in older women.

  View details for DOI 10.1097/gme.0b013e3181f43404

  View details for Web of Science ID 000288781800009

  View details for PubMedID 21127439

• Nutrient Intake and Anemia Risk in the Women's Health Initiative Observational Study JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION Thomson, C. A., Stanaway, J. D., Neuhouser, M. L., Snetselaar, L. G., Stefanick, M. L., Arendell, L., Chen, Z. 2011; 111 (4): 532-541

  Abstract

  Nutrient-related anemia among postmenopausal women is preventable; recent data on prevalence are limited.To investigate the association between nutrient intakes and anemia prevalence, in relation to both incidence and persistence, in a longitudinal sample of postmenopausal women. We hypothesized that anemia prevalence, incidence, and persistence would be greater among women reporting lower intake of vitamin B-12, folate, and iron.Prospective cohort analysis.The observational cohort of the Women's Health Initiative, including 93,676 postmenopausal women, aged 50 to 79 years, who were recruited across the United States at 40 clinical study sites. Women were enrolled between 1993 and 1998; data collection for these analyses continued through 2000.Anemia was defined as a blood hemoglobin concentration of <12.0 g/dL (120.0 g/L). Persistent anemia was defined as anemia present at each measurement time point. Diet was assessed by food frequency questionnaire for iron, folate, B-12, red meat, and cold breakfast cereal; inadequacies were based on dietary reference intakes for women older than age 50 years.Descriptive statistics (mean ± standard deviation) were used to characterize the population demographics, anemia rates, and diet. Unconditional logistic regression was used to investigate associations between diet and incident and persistent anemia. Associations are presented as odds ratio and 95% confidence intervals.Anemia was identified in 3,979 (5.5%) of the cohort. Inadequate intakes of multiple anemia-associated nutrients were less frequent in non-Hispanic whites (7.4%) than other race/ethnic groups (inadequacies demonstrated in 14.6% to 16.3% of the sample). Age, body mass index, and smoking were associated with anemia. Women with anemia reported lower intakes of energy, protein, folate, vitamin B-12, iron, vitamin C, and red meat. Multiple (more than a single nutrient) dietary deficiencies were associated with a 21% greater risk of persistent anemia (odds ratio 1.21, 95% confidence interval 1.05 to 1.41) and three deficiencies resulted in a 44% increase in risk for persistent anemia (odds ratio 1.44, 95% confidence interval 1.20 to 1.73).Inadequate nutrient intake, a modifiable condition, is associated with greater risk for anemia in postmenopausal women participating in the Observational Study of the Women's Health Initiative. Efforts to identify and update incidence estimates for anemia-associated nutrient deficiencies in aging women should be undertaken.

  View details for DOI 10.1016/j.jada.2011.01.017

  View details for Web of Science ID 000289388200009

  View details for PubMedID 21443985

• Poor physical health predicts time to additional breast cancer events and mortality in breast cancer survivors PSYCHO-ONCOLOGY Saquib, N., Pierce, J. P., Saquib, J., Flatt, S. W., Natarajan, L., Bardwell, W. A., Patterson, R. E., Stefanick, M. L., Thomson, C. A., Rock, C. L., Jones, L. A., Gold, E. B., Karanja, N., Parker, B. A. 2011; 20 (3): 252-259

  Abstract

  Health-related quality of life has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors.Women with early-stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association.There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01-10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psychosocial variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher body mass index, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all).Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.

  View details for DOI 10.1002/pon.1742

  View details for Web of Science ID 000288138200003

  View details for PubMedID 20878837

• Biomarker-calibrated Energy and Protein Consumption and Cardiovascular Disease Risk Among Postmenopausal Women EPIDEMIOLOGY Prentice, R. L., Huang, Y., Kuller, L. H., Tinker, L. F., Van Horn, L., Stefanick, M. L., Sarto, G., Ockene, J., Johnson, K. C. 2011; 22 (2): 170-179

  Abstract

  Nutritional epidemiology cohort studies primarily use food frequency questionnaires (FFQs). In part because FFQs are more reliable for nutrient densities than for absolute nutrient consumption, reports from association studies typically present only nutrient density measures in relation to disease risk.We used objective biomarkers to correct FFQ assessments for measurement error, and examined absolute energy and protein consumption in relation to cardiovascular disease incidence. FFQs and subsequent physician-adjudicated cardiovascular disease incidence were assessed for 80,370 postmenopausal women in the age range 50-79 years at enrollment in the comparison group of the Dietary Modification Trial or the prospective Observational Study in the Women's Health Initiative. Urinary recovery biomarkers of energy and protein were obtained from a subsample of 544 women, with concurrent FFQ information.After biomarker correction, energy consumption was positively associated with coronary heart disease incidence (hazard ratio = 1.18; 95% confidence interval = 1.04-1.33, for 20% consumption increment) and protein density was inversely associated (0.85 [0.75-0.97]). The positive energy association appeared to be mediated by body fat accumulation. Ischemic stroke incidence was inversely associated with energy and protein consumption, but not with protein density.A positive association between energy and coronary heart disease risk can be attributed to body mass accumulation. Ischemic stroke risk is inversely associated with energy and protein consumption, possibly due to correlations between consumption and physical activity.

  View details for DOI 10.1097/EDE.0b013e31820839bc

  View details for Web of Science ID 000286970700007

  View details for PubMedID 21206366

• Combined Impact of Geriatric Syndromes and Cardiometabolic Diseases on Measures of Functional Impairment JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Rosso, A. L., Eaton, C. B., Wallace, R., Gold, R., Curb, J. D., Stefanick, M. L., Ockene, J. K., Michael, Y. L. 2011; 66 (3): 349-354

  Abstract

  Examine the independent and joint effects of geriatric syndromes (GS) and cardiometabolic diseases (CMDs) on functional impairment.Cross-sectional analysis of baseline data from the Women's Health Initiative, including 62,829 women aged 65 years or older. GS (urinary incontinence, falls, and depression measured by the shortened Center for Epidemiological Studies-Depression scale/Diagnostic Interview Schedule screening instrument) and CMD (coronary artery disease, coronary heart failure, and diabetes) were self-reported. Physical and social functioning and general health subscales of the Short Form-36 dichotomized at the median for the study sample were used to assess functional impairment. Additive interaction between burden of GS and CMD was assessed using logistic regression models.Forty-three percent of women had at least one GS; 14.1% had at least one CMD; and 6.9% had at least one of each. Compared with women with no GS or CMD, women with one or more GS but no CMD were as likely to have physical functioning impairments (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.73, 1.86) as those with CMD alone (OR = 1.97; CI = 1.84, 2.10). The association with social functioning was stronger for GS alone (OR = 2.10; CI = 2.02, 2.18) compared with CMD (OR = 1.60; CI = 1.50, 1.71). The association with general health was stronger for CMD alone (OR = 2.15; CI = 2.01, 2.29) compared with GS (OR = 1.68; CI = 1.62, 1.74). Significant interactions between GS and CMD were observed for all functional measures with 20%-30% of observed ORs attributable to additive interaction.GSs alone are associated with functional impairment in older women; the association is stronger in the presence of even one CMD.

  View details for DOI 10.1093/gerona/glq230

  View details for Web of Science ID 000288415800013

  View details for PubMedID 21317242

• Reproductive History and Oral Contraceptive Use in Relation to Risk of Triple-Negative Breast Cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Phipps, A. I., Chlebowski, R. T., Prentice, R., McTiernan, A., Wactawski-Wende, J., Kuller, L. H., Adams-Campbell, L. L., Lane, D., Stefanick, M. L., Vitolins, M., Kabat, G. C., Rohan, T. E., Li, C. I. 2011; 103 (6): 470-477

  Abstract

  Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs).Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype.The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

  View details for DOI 10.1093/jnci/djr030

  View details for Web of Science ID 000288554900007

  View details for PubMedID 21346227

• Association of active and passivesmoking with risk of breast cancer among postmenopausal women: a prospective cohort study BRITISH MEDICAL JOURNAL Luo, J., Margolis, K. L., Wactawski-Wende, J., Horn, K., Messina, C., Stefanick, M. L., Tindle, H. A., Tong, E., Rohan, T. E. 2011; 342

  Abstract

  To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women.Prospective cohort study.40 clinical centres in the United States.79,990 women aged 50-79 enrolled in the Women's Health Initiative Observational Study during 1993-8.Self reported active and passive smoking, pathologically confirmed invasive breast cancer.In total, 3520 incident cases of invasive breast cancer were identified during an average of 10.3 years of follow-up. Compared with women who had never smoked, breast cancer risk was elevated by 9% among former smokers (hazard ratio 1.09 (95% CI 1.02 to 1.17)) and by 16% among current smokers (hazard ratio 1.16 (1.00 to 1.34)). Significantly higher breast cancer risk was observed in active smokers with high intensity and duration of smoking, as well as with initiation of smoking in the teenage years. The highest breast cancer risk was found among women who had smoked for ≥ 50 years or more (hazard ratio 1.35 (1.03 to 1.77) compared with all lifetime non-smokers, hazard ratio 1.45 (1.06 to 1.98) compared with lifetime non-smokers with no exposure to passive smoking). An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Among women who had never smoked, after adjustment for potential confounders, those with the most extensive exposure to passive smoking (≥ 10 years' exposure in childhood, ≥ 20 years' exposure as an adult at home, and ≥ 10 years' exposure as an adult at work) had a 32% excess risk of breast cancer compared with those who had never been exposed to passive smoking (hazard ratio 1.32 (1.04 to 1.67)). However, there was no significant association in the other groups with lower exposure and no clear dose response to cumulative passive smoking exposure.Active smoking was associated with an increase in breast cancer risk among postmenopausal women. There was also a suggestion of an association between passive smoking and increased risk of breast cancer.

  View details for DOI 10.1136/bmj.d1016

  View details for Web of Science ID 000288166600009

  View details for PubMedID 21363864

• BMI and Fracture Risk in Older Men: The Osteoporotic Fractures in Men Study (MrOS) JOURNAL OF BONE AND MINERAL RESEARCH Nielson, C. M., Marshall, L. M., Adams, A. L., LeBlanc, E. S., Cawthon, P. M., Ensrud, K., Stefanick, M. L., Barrett-Connor, E., Orwoll, E. S. 2011; 26 (3): 496-502

  Abstract

  Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m(2)); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m(2)), 52% were overweight (25 to 29.9 kg/m(2)), 18% were obese I (30 to 34.9 kg/m(2)), and 3% were obese II (35 to 39.9 kg/m(2)). Overall, nonspine fracture incidence was 16.1 per 1000 person-years, and hip fracture incidence was 3.1 per 1000 person-years. In age-, race-, and BMD-adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87-1.25] for overweight, 1.29 (95% CI 1.00-1.67) for obese I, and 1.94 (95% CI 1.25-3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84-1.23, for overweight; HR = 1.12, 95% CI 0.86-1.46, for obese I, and HR = 1.44, 95% CI 0.90-2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men.

  View details for DOI 10.1002/jbmr.235

  View details for Web of Science ID 000287827600009

  View details for PubMedID 20814955

• Physical activity, additional breast cancer events, and mortality among early-stage breast cancer survivors: findings from the WHEL Study CANCER CAUSES & CONTROL Bertram, L. A., Stefanick, M. L., Saquib, N., Natarajan, L., Patterson, R. E., Bardwell, W., Flatt, S. W., Newman, V. A., Rock, C. L., Thomson, C. A., Pierce, J. P. 2011; 22 (3): 427-435

  Abstract

  Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.A total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.

  View details for DOI 10.1007/s10552-010-9714-3

  View details for Web of Science ID 000288542400010

  View details for PubMedID 21184262

• Mortality Risk in Older Men Associated with Changes in Weight, Lean Mass, and Fat Mass JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Lee, C. G., Boyko, E. J., Nielson, C. M., Stefanick, M. L., Bauer, D. C., Hoffman, A., Dam, T. L., Lapidus, J. A., Cawthon, P. M., Ensrud, K. E., Orwoll, E. S. 2011; 59 (2): 233-240

  Abstract

  To evaluate risk of all-cause mortality associated with changes in body weight, total lean mass, and total fat mass in older men.Longitudinal cohort study.Six U.S. clinical centers.Four thousand three hundred thirty-one ambulatory men aged 65 to 93 at baseline.Repeated measurements of body weight and total lean and fat mass were taken using dual-energy X-ray absorptiometry 4.6 ± 0.4 years apart. Percentage changes in these measures were categorized as gain (+5%), loss (-5%), or stable (-5% to +5%). Deaths were verified centrally according to death certificate reviews, and proportional hazard models were used to estimate the risk of mortality.After accounting for baseline lifestyle factors and medical conditions, a higher risk of mortality was found for men with weight loss (hazard rat (HR)=1.84, 95% confidence interval (CI)=1.50-2.26), total lean mass loss (HR=1.78, 95% CI=1.45-2.19), and total fat mass loss (HR=1.72, 95% CI=1.34-2.20) than for men who were stable for each body composition measure. Men with total fat mass gain had a slightly greater mortality risk (HR=1.29, 95% CI=0.99-1.67) than those who remained stable. These associations did not differ according to baseline age, obesity, or self-reported health status (P for interactions >.10), although self-reported weight loss intent altered mortality risks with total fat mass (P for interaction=.04) and total lean mass (P for interaction=.09) change.Older men who lost weight, total lean mass, or total fat mass had a higher risk of mortality than men who remained stable.

  View details for DOI 10.1111/j.1532-5415.2010.03245.x

  View details for Web of Science ID 000287240700006

  View details for PubMedID 21288234

• Rest/Activity Rhythms and Cardiovascular Disease in Older Men CHRONOBIOLOGY INTERNATIONAL Paudel, M. L., Taylor, B. C., Ancoli-Israel, S., Stone, K. L., Tranah, G., Redline, S., Barrett-Connor, E., Stefanick, M. L., Ensrud, K. E. 2011; 28 (3): 258-266

  Abstract

  Prior studies have suggested an increased risk of cardiovascular disease (CVD)-related mortality in older adults with disturbed circadian rest/activity rhythms (RARs). The objective goal of this study was to examine the association between disrupted RARs and risk of CVD events in older men. A total of 2968 men aged 67 yrs and older wore wrist actigraphs for 115 ± 18 consecutive hours. RAR parameters were computed from wrist actigraphy data and expressed as quartiles (Q). CVD events consisted of a composite outcome of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) events. Secondary analyses examined associations between RARs and individual components of the composite outcome (CHD, stroke, and PVD). There were 490 CVD events over an average of 4.0 ± 1.2 yrs. Overall, reduced amplitude (HR = 1.31, 95% confidence interval [CI] 1.01-1.71 for Q2 vs. Q4) and greater minimum (HR = 1.33, 95% CI 1.01-1.73 for Q4 vs. Q1) were associated with an increased risk of CVD events in multivariable-adjusted models. In secondary analyses, there was an independent association between reduced amplitude (HR = 1.36, 95% CI 1.00-1.86) and greater minimum activity counts (HR = 1.39, 95% CI 1.02-1.91) with increased risk of CHD events. Reduced F value (HR = 2.88, 95% CI 1.41-5.87 for Q1 vs. Q4 and HR = 2.71, 95% CI 1.34-5.48 for Q2 vs. Q4) and later occurring acrophase of the RAR (HR = 1.65, 95% CI 1.04-2.63 for Q4 vs. Q2-3) were associated with an increased risk of PVD events. Results were similar in men without a history of CVD events. The findings revealed that among older men, measures of decreased circadian activity rhythm robustness (reduced amplitude and greater minimum activity) were associated with an increased risk of CVD events, primarily through increased risk of CHD or stroke events, whereas measures of reduced circadian activity rhythmicity were not associated with risk of CVD events overall, but were associated with an increased risk of PVD events. These results should be confirmed in other populations.

  View details for DOI 10.3109/07420528.2011.553016

  View details for Web of Science ID 000289000900008

  View details for PubMedID 21452921

• Circulating 25-Hydroxyvitamin D Levels and Frailty in Older Men: The Osteoporotic Fractures in Men Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Ensrud, K. E., Blackwell, T. L., Cauley, J. A., Cummings, S. R., Barrett-Connor, E., Dam, T. L., Hoffman, A. R., Shikany, J. M., Lane, N. E., Stefanick, M. L., Orwoll, E. S., Cawthon, P. M. 2011; 59 (1): 101-106

  Abstract

  To determine the cross-sectional and longitudinal associations between 25-hydroxyvitamin D (25(OH)D) levels and frailty status in older men.Prospective cohort study.Six U.S. community-based centers.One thousand six hundred six men aged 65 and older.25(OH)D (liquid chromatography tandem mass spectroscopy) and frailty status (criteria similar to those used in the Cardiovascular Health Study) measured at baseline; frailty status assessment repeated an average of 4.6 years later. Frailty status was classified as robust, intermediate, or frail at baseline and robust, intermediate, frail, or dead at follow-up.After adjusting for multiple potential confounders, men with 25(OH)D levels less than 20.0 ng/mL had 1.5 times higher odds (multivariate odds ratio (MOR)=1.47, 95% confidence interval (CI)=1.07-2.02) of greater frailty status at baseline than men with 25(OH)D levels of 30.0 ng/mL or greater (referent group), whereas frailty status was similar in men with 25(OH)D levels from 20.0 to 29.9 ng/mL and those with levels of 30.0 ng/mL or greater (MOR=1.02, 95% CI=0.78-1.32). However, in 1,267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6-year follow-up. Findings were the same when 25(OH)D was expressed in quartiles or as a continuous variable.Lower levels of 25(OH)D (<20.0 ng/mL) in community-dwelling older men were independently associated with greater evidence of frailty at baseline but did not predict greater risk of greater frailty status at 4.6 years.

  View details for DOI 10.1111/j.1532-5415.2010.03201.x

  View details for Web of Science ID 000286208200015

  View details for PubMedID 21226680

• Recreational physical activity, anthropometric factors, and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women CANCER CAUSES & CONTROL Kabat, G. C., Kim, M., Wactawski-Wende, J., Lane, D., Adams-Campbell, L. L., Gaudet, M., Stefanick, M. L., Vitolins, M., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2010; 21 (12): 2173-2181

  Abstract

  To assess the association of recreational physical activity and anthropometric factors in relation to risk of ductal carcinoma in situ (DCIS) of the breast.The association was examined in a cohort of 58,055 postmenopausal women participating in the Women's Health Initiative (WHI) clinical trials, among whom 450 cases of DCIS were ascertained after a median follow-up of 8.0 years. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).After adjustment for covariates, the hazard ratio for DCIS among women with ≥ 20 metabolic equivalent task-hours per week (MET-h/week) of total recreational physical activity compared to women who did not engage in any recreational physical activity (0 MET-h/week) was 0.97 (95% CI 0.70-1.34). Neither body mass index nor waist circumference was associated with risk. In addition, physical activity and anthropometric factors were not associated with risk of either high-grade or low-/moderate-grade DCIS.Recreational physical activity and anthropometric factors showed no association with risk of DCIS in postmenopausal women in the WHI clinical trial.

  View details for DOI 10.1007/s10552-010-9637-z

  View details for Web of Science ID 000288609600025

  View details for PubMedID 20814736

• Sex differences in the prevalence of peripheral artery disease in patients undergoing coronary catheterization VASCULAR MEDICINE Rafie, A. H., Stefanick, M. L., Sims, S. T., Phan, T., Higgins, M., Gabriel, A., Assimes, T., Narasimhan, B., Nead, K. T., Myers, J., Olin, J., Cooke, J. P. 2010; 15 (6): 443-450

  Abstract

  To determine whether there are sex differences in the prevalence of peripheral artery disease, we performed an observational study of 1014 men and 547 women, aged ≥ 40 years, referred for elective coronary angiography. Women were slightly older, more obese, had higher low-density lipoprotein cholesterol (LDL-C) levels and systolic blood pressure (BP), and were more likely to be African American. Women had higher high-density lipoprotein cholesterol (HDL-C) levels, lower diastolic BP, and were less likely to smoke or to have a history of cardiovascular disease. Women had less prevalent (62% vs 81%) and less severe coronary artery disease (CAD) (p < 0.001 for both) by coronary angiography, but more prevalent peripheral artery disease (PAD) as determined by the ankle-brachial index (ABI) than men (23.6% versus 17.2%). Independent predictors of lower ABI were female sex, black race, older age, tobacco use, CAD, diabetes, and triglyceride level. In a full multivariable logistic regression model, women had a risk-adjusted odds ratio for PAD of 1.78 (95% CI 1.25-2.54) relative to men. Among patients referred for coronary angiography, women have less prevalent and less severe CAD, but more prevalent PAD, a sex difference that is not explained by traditional cardiovascular disease risk factors or CAD severity. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00380185.

  View details for DOI 10.1177/1358863X10388345

  View details for Web of Science ID 000285574400002

  View details for PubMedID 21183651

• Vasomotor symptoms and coronary artery calcium in postmenopausal women MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Allison, M. A., Manson, J. E., Aragaki, A., Langer, R. D., Rossouw, J., Curb, D., Martin, L. W., Phillips, L., Stefanick, M. L., Cochrane, B. B., Sarto, G., Barnhart, J., O'Sullivan, M. J., Johnson, K. C., Gass, M., Trevisan, M., Woods, N. F. 2010; 17 (6): 1136-1145

  Abstract

  We assessed whether vasomotor symptoms (VMS) are associated with coronary artery calcium (CAC) and how hormone therapy (HT) may influence this association.Participants were a subset of women aged 50 to 59 years with a history of hysterectomy who were enrolled in the Women's Health Initiative (WHI) estrogen-alone clinical trial and underwent a CT scan of the chest at the end of the trial to determine CAC. Participants provided information about VMS (hot flashes and/or night sweats), as well as HT use, on self-administered questionnaires at trial baseline.The sample consisted of 918 women with a mean (SD) age of 55.1 (2.8) years at WHI randomization and 64.8 (2.9) years at CAC ascertainment. The prevalence of a CAC score higher than 0 was 46%, whereas the prevalence of a CAC score of 10 or higher and higher than 100 was 39% and 19%, respectively. At randomization, 77% reported a history of any VMS at any time before or at enrollment in the WHI, whereas 20% reported any VMS present only at enrollment. Compared with those without a history of any VMS and after adjustment for potential confounders, a history of any VMS at any time up to and including WHI enrollment was associated with significantly reduced odds for CAC higher than 0 (odds ratio, 0.66; 95% CI, 0.45-0.98). Moreover, as duration of HT increased, the inverse association between any VMS and CAC moved toward the null.A history of any VMS was significantly associated with reduced odds for CAC independent of traditional cardiovascular disease risk factors and other relevant covariates. This association seems to be influenced by duration of HT.

  View details for DOI 10.1097/gme.0b013e3181e664dc

  View details for Web of Science ID 000283993700011

  View details for PubMedID 20651617

• Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chlebowski, R. T., Anderson, G. L., Gass, M., Lane, D. S., Aragaki, A. K., Kuller, L. H., Manson, J. E., Stefanick, M. L., Ockene, J., Sarto, G. E., Johnson, K. C., Wactawski-Wende, J., Ravdin, P. M., Schenken, R., Hendrix, S. L., Rajkovic, A., Rohan, T. E., Yasmeen, S., Prentice, R. L. 2010; 304 (15): 1684-1692

  Abstract

  In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported.To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009.A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants.Invasive breast cancer incidence and breast cancer mortality.In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group.Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.clinicaltrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000283129700022

  View details for PubMedID 20959578

• Gendered Innovations: A New Approach for Nursing Science BIOLOGICAL RESEARCH FOR NURSING Sims, S. T., Stefanick, M. L., Kronenberg, F., Sachedina, N. A., Schiebinger, L. 2010; 12 (2): 156-161

  Abstract

  Considerable sex and gender bias has been recognized within the field of medicine. Investigators have used sex and gender analysis to reevaluate studies and outcomes and generate new perspectives and new questions regarding differential diagnoses and treatments of men and women. Sex and gender analysis acts as an experimental control to provide critical scientific rigor; researchers who ignore it risk ignoring a possible source of error in past, current, and future science. In this article, the authors introduce some tools of sex and gender analysis and illustrate the concept of gendered innovations by demonstrating through examples how this type of analysis has profoundly enhanced human knowledge in health and disease. The authors also provide recommendations for incorporating the concepts of sex and gender analysis into nursing education and research.

  View details for DOI 10.1177/1099800410375108

  View details for Web of Science ID 000281796300006

  View details for PubMedID 20798156

• Evidence for Geographical and Racial Variation in Serum Sex Steroid Levels in Older Men JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Orwoll, E. S., Nielson, C. M., Labrie, F., Barrett-Connor, E., Cauley, J. A., Cummings, S. R., Ensrud, K., Karlsson, M., Lau, E., Leung, P. C., Lunggren, O., Mellstrom, D., Patrick, A. L., Stefanick, M. L., Nakamura, K., Yoshimura, N., Zmuda, J., Vandenput, L., Ohlsson, C. 2010; 95 (10): E151-E160

  Abstract

  Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men.Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay.There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites.On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.

  View details for DOI 10.1210/jc.2009-2435

  View details for Web of Science ID 000282573300041

  View details for PubMedID 20668046

• Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Brunner, R. L., Aragaki, A., Barnabei, V., Cochrane, B. B., Gass, M., Hendrix, S., Lane, D., Ockene, J., Woods, N. F., Yasmeen, S., Stefanick, M. 2010; 17 (5): 946-954

  Abstract

  The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.

  View details for DOI 10.1097/gme.0b013e3181d76953

  View details for Web of Science ID 000281614700013

  View details for PubMedID 20505547

• Lung Cancer Among Postmenopausal Women Treated With Estrogen Alone in the Women's Health Initiative Randomized Trial JOURNAL OF THE NATIONAL CANCER INSTITUTE Chlebowski, R. T., Anderson, G. L., Manson, J. E., Schwartz, A. G., Wakelee, H., Gass, M., Rodabough, R. J., Johnson, K. C., Wactawski-Wende, J., Kotchen, J. M., Ockene, J. K., O'Sullivan, M. J., Hubbell, F. A., Chien, J. W., Chen, C., Stefanick, M. L. 2010; 102 (18): 1413-1421

  Abstract

  In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer.The WHI study is a randomized, double-blind, placebo-controlled trial conducted in 40 centers in the United States. A total of 10 739 postmenopausal women aged 50-79 years who had a previous hysterectomy were randomly assigned to receive a once-daily 0.625-mg tablet of conjugated equine estrogen (n = 5310) or matching placebo (n = 5429). Incidence and mortality rates for all lung cancers, small cell lung cancers, and non-small cell lung cancers in the two randomization groups were compared by use of hazard ratios (HRs) and 95% confidence intervals (CIs) that were estimated from Cox proportional hazards regression analyses. Analyses were by intention to treat, and all statistical tests were two-sided.After a mean of 7.9 years (standard deviation = 1.8 years) of follow-up, 61 women in the hormone therapy group were diagnosed with lung cancer compared with 54 in the placebo group (incidence of lung cancer per year = 0.15% vs 0.13%, respectively; HR of incidence = 1.17, 95% CI = 0.81 to 1.69, P = .39). Non-small cell lung cancers were of comparable number, stage, and grade in both groups. Deaths from lung cancer did not differ between the two groups (34 vs 33 deaths in estrogen and placebo groups, respectively; HR of death = 1.07, 95% CI = 0.66 to 1.72, P = .79).Unlike use of estrogen plus progestin, which increased deaths from lung cancer, use of conjugated equine estrogen alone did not increase incidence or death from lung cancer.

  View details for DOI 10.1093/jnci/djq285

  View details for Web of Science ID 000282176600010

  View details for PubMedID 20709992

  View details for PubMedCentralID PMC2943522

• Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kabat, G. C., Kim, M., Shikany, J. M., Rodgers, A. K., Wactawski-Wende, J., Lane, D., Powell, L., Stefanick, M. L., Freiberg, M. S., Kazlauskaite, R., Chlebowski, R. T., Wassertheil-Smoller, S., Rohan, T. E. 2010; 19 (8): 2066-2072

  Abstract

  Observational studies have commonly linked higher alcohol consumption with a modest increase in invasive breast cancer risk, but cohort studies have not examined alcohol intake in relation to ductal carcinoma in situ (DCIS).The association between adulthood alcohol consumption assessed at baseline and subsequent DCIS risk was examined in a cohort of postmenopausal women participating in the Women's Health Initiative clinical trials, in which mammography was protocol-mandated. Alcohol intake was assessed by a semiquantitative food-frequency questionnaire. Reported DCIS cases were verified by central pathology report review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.The cohort consisted of 63,822 women with information on alcohol intake, among whom 489 cases of DCIS were ascertained after a median follow-up of 8.0 years. For the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date of diagnosis of invasive breast cancer. After adjustment for covariates, the hazard ratio for DCIS among women who consumed 14 or more servings of alcohol per week, relative to nondrinkers, was 0.87 (95% confidence interval, 0.50-1.51). In addition, alcohol intake was not associated with risk of either high-grade or low-/moderate-grade DCIS.In this large cohort study of postmenopausal women, alcohol consumption was not associated with risk of DCIS.If other studies confirm our findings, this would suggest that alcohol may have an effect later in the carcinogenic process.

  View details for DOI 10.1158/1055-9965.EPI-10-0388

  View details for Web of Science ID 000280675000020

  View details for PubMedID 20647412

• Bone mineral density and prevalent osteoarthritis of the hip in older men for the Osteoporotic Fractures in Men (MrOS) Study Group OSTEOPOROSIS INTERNATIONAL Chaganti, R. K., Parimi, N., Lang, T., Orwoll, E., Stefanick, M. L., Nevitt, M., Lane, N. E. 2010; 21 (8): 1307-1316

  Abstract

  We evaluated the association of bone mineral density (BMD) and osteoarthritis (OA) of the hip in elderly men. We found that elderly men with moderate to severe radiographic hip OA (RHOA) had significantly higher areal BMD (aBMD) and volumetric BMD (vBMD) at both the lumbar spine and hip compared to age similar controls without OA.We evaluated the association of BMD measured by dual energy X-ray absorptiometry (DXA) and quantitative computerized tomography (integral, cortical, and trabecular vBMD) and RHOA in a cohort of elderly men.A cross-sectional analysis was conducted within the Study of Osteoporotic Fractures in Men, a prospective cohort study of 5,995 US men age > or = 65 years. Standing pelvic x-rays were done in 4,024 subjects and scored for prevalent RHOA severity. DXA was done in 3,886 subjects, and aBMD and vBMD associations were compared with RHOA score using linear regression, adjusting for covariates.Both moderate and severe RHOA groups had significantly higher aBMD at all BMD sites (range, 3.7-10.0% difference; p value 0.0012 and p value < 0.005) compared to the control group with no RHOA. The difference remained strong after adjusting for covariates. While the total hip and lumbar spine cortical vBMD measurements of subjects with moderate or severe RHOA was increased compared to controls, trabecular vBMD was not.Older men, with both moderate and severe RHOA, had significantly higher aBMD and integral vBMD at the hip and lumbar spine compared to controls without RHOA.

  View details for DOI 10.1007/s00198-009-1105-9

  View details for Web of Science ID 000279478500003

  View details for PubMedID 20101493

• Postmenopausal hormone therapy and cardiovascular disease in women NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES Stefanick, M. L. 2010; 20 (6): 451-458

  Abstract

  The belief in the hypothesis of cardiovascular benefit of hormone therapy (HT) in postmenopausal women was widespread; however, the Women's Health Initiative (WHI) hormone trials found no evidence of coronary heart disease (CHD) benefit among women aged 50-79 with no prior CHD diagnosis and HT increased risk of stroke. This article reviews the literature regarding HT and CHD, with emphasis on the findings from the WHI trials.Findings from observational studies and animal studies addressing biological plausibility that had been interpreted as evidence to support the use of HT were reviewed and findings from the trials of women with cardiovascular disease and the WHI hormone trials are summarized, with specific commentary on the issue of differential effects of HT in younger versus older women.HT should not be prescribed for the purpose of preventing cardiovascular disease. The WHI offered support for the current U.S. Food and Drug Administration recommendation to limit HT to short-term use. There is a clear need for a greater understanding of the effects of both endogenous and exogenous estrogens in relationship to the aging cardiovascular system.

  View details for DOI 10.1016/j.numecd.2010.02.015

  View details for Web of Science ID 000281612200011

  View details for PubMedID 20554177

• Estrogen Alone in Postmenopausal Women and Breast Cancer Detection by Means of Mammography and Breast Biopsy JOURNAL OF CLINICAL ONCOLOGY Chlebowski, R. T., Anderson, G., Manson, J. E., Pettinger, M., Yasmeen, S., Lane, D., Langer, R. D., Hubbell, F. A., McTiernan, A., Hendrix, S., Schenken, R., Stefanick, M. L. 2010; 28 (16): 2690-2697

  Abstract

  As the influence of estrogen alone on breast cancer detection is not established, we examined this issue in the Women's Health Initiative trial, which randomly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen (CEE; 0.625 mg/d) or placebo.Screening mammography and breast exams were performed at baseline and annually. Breast biopsies were based on clinical findings. Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic (ROC) analyses of mammogram performance.After a 7.1-year mean follow-up, fewer invasive breast cancers were diagnosed in the CEE than in the placebo group, but the difference was not statistically significant. Use of CEE alone increased mammograms with short-interval follow-up recommendations (cumulative, 39.2% v 29.6.3%; P < .001) but not abnormal mammograms (ie, those suggestive of or highly suggestive of malignancy; cumulative, 7.3% v 7.0%; P = .41). Breast biopsies were more frequent in the CEE group (cumulative, 12.5% v 10.7%; P = .004) and less commonly diagnosed as cancer (8.9% v 15.8%, respectively, with positive biopsies; P = .04). Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use.CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies, respectively. Although the breast biopsies on CEE were less commonly diagnosed as cancer, breast cancer detection was not substantially compromised. These findings differ from estrogen-plus-progestin use, for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen.

  View details for DOI 10.1200/JCO.2009.24.8799

  View details for Web of Science ID 000278108800007

  View details for PubMedID 20439627

• Estrogen Alone and Lung Cancer in Postmenopausal Women Chlebowski, R., Anderson, G., Manson, J., Schwartz, A., Wakelee, H., Gass, M., Rodabough, R., Johnson, K., Wactawski-Wende, J., Stefanick, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2010: 394–94

  View details for Web of Science ID 000277538600050

• Physical Activity Resources and Changes in Walking in a Cohort of Older Men AMERICAN JOURNAL OF PUBLIC HEALTH Michael, Y. L., Perdue, L. A., Orwoll, E. S., Stefanick, M. L., Marshall, L. M. 2010; 100 (4): 654-660

  Abstract

  We evaluated the influence of physical activity resources and neighborhood-level socioeconomic status (SES) on walking among community-dwelling older men.Participants reported time walked per day at baseline (2000-2002) and follow-up. Residential addresses were linked to a geographic information system database to assess proximity to parks, trails, and recreational facilities. Log-binomial regression analyses were conducted to test the hypothesis that men living near physical activity resources were more likely to increase or maintain time walked.Average time walked per day declined by 6 minutes between baseline and follow-up (P < .05). There was a significant interaction of neighborhood SES and physical activity with walking time (P < .1). Proximity to parks and proximity to trails, respectively, were associated with a 22% (95% confidence interval [CI] = 1.01, 1.47) and 34% (95% CI = 1.16, 1.55) higher likelihood of maintaining or increasing walking time in high-SES neighborhoods, but there was no association in low-SES neighborhoods. Proximity to recreational facilities was not associated with walking.Uncovering reasons that proximity to parks and trails is not associated with maintenance of walking activity among men in low-SES neighborhoods could provide new insight into ways to promote physical activity.

  View details for DOI 10.2105/AJPH.2009.172031

  View details for Web of Science ID 000275937200017

  View details for PubMedID 20167887

• Association between sex steroids and cognition in elderly men CLINICAL ENDOCRINOLOGY LeBlanc, E. S., Wang, P. Y., Janowsky, J. S., Neiss, M. B., Fink, H. A., Yaffe, K., Marshall, L. M., Lapidus, J. A., Stefanick, M. L., Orwoll, E. S. 2010; 72 (3): 393-403

  Abstract

  To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men.Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older.One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined.Baseline and follow-up (4.5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression.Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0.03) and 3MS performance (P = 0.02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance.Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

  View details for DOI 10.1111/j.1365-2265.2009.03692.x

  View details for Web of Science ID 000274438600017

  View details for PubMedID 19744108

• Metabolic Syndrome and Changes in Body Fat From a Low-fat Diet and/or Exercise Randomized Controlled Trial OBESITY Camhi, S. M., Stefanick, M. L., Katzmarzyk, P. T., Young, D. R. 2010; 18 (3): 548-554

  Abstract

  It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight-stable randomized controlled trial of low-fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (DeltaMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (DeltaBF) as a covariate. In men, DeltaMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, DeltaMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for DeltaBF, all differences between groups were attenuated and no longer significant. DeltaMetS were associated with DeltaBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for DeltaBF, low-fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low-fat diet and/or increased physical activity appears to be body fat loss.

  View details for DOI 10.1038/oby.2009.304

  View details for Web of Science ID 000275024100018

  View details for PubMedID 19798074

• Relative Effects of Tamoxifen, Raloxifene, and Conjugated Equine Estrogens on Cognition JOURNAL OF WOMENS HEALTH Espeland, M. A., Shumaker, S. A., Limacher, M., Rapp, S. R., Bevers, T. B., Barad, D. H., Coker, L. H., Gaussoin, S. A., Stefanick, M. L., Lane, D. S., Maki, P. M., Resnick, S. M. 2010; 19 (3): 371-379

  Abstract

  To compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years.Annual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function in the two randomized placebo-controlled clinical trials of CEE therapies of the Women's Health Initiative Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential ethnic-related differences between studies, to Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with placebo therapy while controlling for differences between groups with respect to dementia risk factors.At baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was associated with a small mean relative deficit in 3MS scores of < or =0.5 units, which was fairly consistent between women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001) and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative deficits appeared to be greater among women with lower baseline 3MS scores: p = 0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE).Although unmeasured differences between trials may have confounded analyses, these findings raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women; however, the magnitude of the effect is small, and the long-term consequences are unknown.

  View details for DOI 10.1089/jwh.2009.1605

  View details for Web of Science ID 000275983200002

  View details for PubMedID 20136553

• The Relationship Between Cognitive Function and Physical Performance in Older Women: Results From the Women's Health Initiative Memory Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Atkinson, H. H., Rapp, S. R., Williamson, J. D., Lovato, J., Absher, J. R., Gass, M., Henderson, V. W., Johnson, K. C., Kostis, J. B., Sink, K. M., Mouton, C. P., Ockene, J. K., Stefanick, M. L., Lane, D. S., Espeland, M. A. 2010; 65 (3): 300-306

  Abstract

  Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear.In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change.Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p

  View details for DOI 10.1093/gerona/glp149

  View details for Web of Science ID 000275420800014

  View details for PubMedID 19789197

• Migraine History and Breast Cancer Risk Among Postmenopausal Women JOURNAL OF CLINICAL ONCOLOGY Li, C. I., Mathes, R. W., Bluhm, E. C., Caan, B., Cavanagh, M. F., Chlebowski, R. T., Michael, Y., O'Sullivan, M. J., Stefanick, M. L., Prentice, R. 2010; 28 (6): 1005-1010

  Abstract

  PURPOSE Both migraine and breast cancer are hormonally mediated. Two recent reports indicate that women with a migraine history may have a lower risk of postmenopausal breast cancer than those who never suffered migraines. This finding requires confirmation; in particular, an assessment of the influence of use of nonsteroidal anti-inflammatory drugs (NSAID) is needed, because many studies indicate that NSAID use also may confer a reduction in breast cancer risk. METHODS We assessed the relationship between self-reported history of migraine and incidence of postmenopausal breast cancer in 91,116 women enrolled on the Women's Health Initiative Observational Study prospective cohort from 1993 to 1998 at ages 50 to 79 years. Through September 15, 2005, there were 4,006 eligible patients with breast cancer diagnosed. Results Women with a history of migraine had a lower risk of breast cancer (hazard ratio [HR], 0.89; 95% CI, 0.80 to 98) than women without a migraine history. This risk did not vary by recent NSAID use. The lower risk was somewhat more pronounced for invasive estrogen-receptor-positive and progesterone-receptor-positive tumors (HR, 0.83; 95% CI, 0.71 to 0.97), as no reduction in risk was observed for invasive ER-negative/PR-negative tumors (HR, 1.16; 95% CI, 0.86 to 1.57), and this difference in risk estimates was borderline statistically significant (P = .06). CONCLUSION This study supports the hypothesis that a history of migraine is associated with a lower risk of breast cancer and that this relationship is independent of recent NSAID use.

  View details for DOI 10.1200/JCO.2009.25.0423

  View details for Web of Science ID 000274653200018

  View details for PubMedID 20100960

• Changes in C-reactive protein from low-fat diet and/or physical activity in men and women with and without metabolic syndrome METABOLISM-CLINICAL AND EXPERIMENTAL Camhi, S. M., Stefanick, M. L., Ridker, P. M., Young, D. R. 2010; 59 (1): 54-61

  Abstract

  Change in high-sensitivity C-reactive protein (CRP) from low-fat diet (diet) and physical activity (PA) interventions is relatively unknown for adults with metabolic syndrome. The objective of the study was to assess CRP change (DeltaCRP) with diet and/or PA in men and women with and without metabolic syndrome. Men (n = 149) and postmenopausal women (n = 125) with elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol were recruited into a 1-year randomized controlled trial. Treatment groups were as follows: control, diet (reduced total fat, saturated fat, and cholesterol intake), PA (45-60 minutes at 60%-85% maximum heart rate), or diet + PA. Weight loss was not an intervention focus. Metabolic syndrome was defined using the American Heart Association/National Heart, Lung, and Blood Institute criteria. Stored plasma samples were analyzed for CRP. Change in CRP was compared between treatments, within sex and metabolic syndrome status, using analysis of covariance, including covariates for baseline CRP and body fat change. For women with metabolic syndrome (n = 39), DeltaCRP was greater in diet vs control (-1.2 +/- 0.4, P = .009), diet + PA vs control (-1.3 +/- 0.4, P = .006), and diet + PA vs PA (-1.1 +/- 0.4, P = .02). Women with metabolic syndrome receiving the diet component (diet or diet + PA) had greater DeltaCRP compared with those who did not (control or PA) (P = .001). Change in CRP was not significantly different between intervention groups in men overall, women overall, men with (n = 47) or without metabolic syndrome (n = 102), or women without metabolic syndrome (n = 86). Low-fat diet may be the most effective treatment for reducing CRP in women with metabolic syndrome.

  View details for DOI 10.1016/j.metabol.2009.07.008

  View details for Web of Science ID 000276761500009

  View details for PubMedID 19709693

• Family history of later-onset breast cancer, breast healthy behavior and invasive breast cancer among postmenopausal women: a cohort study BREAST CANCER RESEARCH Gramling, R., Lash, T. L., Rothman, K. J., Cabral, H. J., Silliman, R., Roberts, M., Stefanick, M. L., Harrigan, R., Bertoia, M. L., Eaton, C. B. 2010; 12 (5)

  Abstract

  A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention--including maintaining a healthful body weight, being physically active and limiting alcohol intake--modifies breast cancer risk attributed to FHLBC in postmenopausal women.Breast cancer outcomes through August 2003 were analyzed in relationship to lifestyle and risk factors collected by questionnaire during enrollment (between 1993 and 1998) of 85,644 postmenopausal women into the Women's Health Initiative Observational Study.During a mean follow-up of 5.4 years, 1997 women were diagnosed with invasive breast cancer. The rate of invasive breast cancer among women with an FHLBC who participated in all three behaviors was 5.94 per 1,000 woman-years, compared with 6.97 per 1,000 woman-years among women who participated in none of the behaviors. The rate among women with no FHLBC who participated in all three behavioral conditions was 3.51 per 1,000 woman-years compared to 4.67 per 1,000 woman-years for those who participated in none. We did not observe a clinically important departure from additive effects (Interaction Contrast: 0.00014; 95% CI: -0.00359, 0.00388).Participating in breast healthy behaviours was beneficial to postmenopausal women and the degree of this benefit was the same for women with and without an FHLBC.

  View details for DOI 10.1186/bcr2727

  View details for Web of Science ID 000285506100017

  View details for PubMedID 20939870

• Independent Clinical Correlates of Atrial Fibrillation in Postmenopausal Women: The Women's Health Initiative Observational Study 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Klein, L., Connelly, S., Larson, J., Limacher, M., Manson, J., Martin, L. W., Prineas, R., Rodriguez, B. L., Smoller, S., Soliman, E., Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2009: S520–S520

  View details for Web of Science ID 000271831501093

• Effects of Postmenopausal Hormone Therapy on Atrial Fibrillation: The Women's Health Initiative Randomized Controlled Trials 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Perez, M., Wang, P. J., Cochrane, B., Curb, J. D., Klein, L., Larson, J., Manson, J., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. LIPPINCOTT WILLIAMS & WILKINS. 2009: S519–S519

  View details for Web of Science ID 000271831501090

• Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women with Prior Hysterectomy JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Resnick, S. M., Espeland, M. A., An, Y., Maki, P. M., Coker, L. H., Jackson, R., Stefanick, M. L., Wallace, R., Rapp, S. R. 2009; 94 (11): 4152-4161

  Abstract

  Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women.The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy.This was a randomized, double blind, placebo-controlled clinical trial.The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers.Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr.Intervention was 0.625 mg of CEE daily or placebo.Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect.CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women.

  View details for DOI 10.1210/jc.2009-1340

  View details for Web of Science ID 000271470800006

  View details for PubMedID 19850684

• Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial LANCET Chlebowski, R. T., Schwartz, A. G., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Rodabough, R. J., Chien, J. W., Wactawski-Wende, J., Gass, M., Kotchen, J. M., Johnson, K. C., O'Sullivan, M. J., Ockene, J. K., Chen, C., Hubbell, F. A. 2009; 374 (9697): 1243-1251

  Abstract

  In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611.After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups.Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.National Heart, Lung and Blood Institute, National Institutes of Health.

  View details for DOI 10.1016/S0140-6736(09)61526-9

  View details for Web of Science ID 000270852500030

  View details for PubMedID 19767090

• Histories including number of falls may improve risk prediction for certain non-vertebral fractures in older men INJURY PREVENTION Faulkner, K. A., Chan, B. K., Cauley, J. A., Marshall, L. M., Ensrud, K. E., Stefanick, M. L., Orwoll, E. S. 2009; 15 (5): 307-311

  Abstract

  To determine whether information on number of falls on a falls history screen predicts risk of non-vertebral and hip fracture.A cohort of 5995 community-dwelling men aged 65 years and older (mean 73.7) was followed over 7.2 years for incident non-vertebral fractures. Cox proportional hazard models were used to calculate hazard ratios (HRs) (95% CI) for incident fracture comparing a history of one and two or more falls with no falls. Models were adjusted for age, clinic, body mass index, height, femoral neck bone mineral density and whether the participant had a non-trauma fracture after the age of 50. p

  View details for DOI 10.1136/ip.2009.021915

  View details for Web of Science ID 000270485400004

  View details for PubMedID 19805598

• Sex Hormones and Frailty in Older Men: The Osteoporotic Fractures in Men (MrOS) Study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Cawthon, P. M., Ensrud, K. E., Laughlin, G. A., Cauley, J. A., Dam, T. L., Barrett-Connor, E., Fink, H. A., Hoffman, A. R., Lau, E., Lane, N. E., Stefanick, M. L., Cummings, S. R., Orwoll, E. S. 2009; 94 (10): 3806-3815

  Abstract

  As men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors.The aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status.The Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers.A total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later.Proportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods.In cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment.Low levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.

  View details for DOI 10.1210/jc.2009-0417

  View details for Web of Science ID 000270526500025

  View details for PubMedID 19737923

  View details for PubMedCentralID PMC2758722

• Vasomotor Symptoms, Adoption of a Low-Fat Dietary Pattern, and Risk of Invasive Breast Cancer: A Secondary Analysis of the Women's Health Initiative Randomized Controlled Dietary Modification Trial JOURNAL OF CLINICAL ONCOLOGY Caan, B. J., Aragaki, A., Thomson, C. A., Stefanick, M. L., Chlebowski, R., Hubbell, F. A., Tinker, L., Vitolins, M., Rajkovic, A., Bueche, M., Ockene, J. 2009; 27 (27): 4500-4507

  Abstract

  To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms.Postmenopausal women age 50 to 79 years enrolled onto the Women's Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators.Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata.The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.

  View details for DOI 10.1200/JCO.2008.20.0493

  View details for Web of Science ID 000270019900012

  View details for PubMedID 19687338

• A Longitudinal Study of the Metabolic Syndrome and Risk of Postmenopausal Breast Cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Kabat, G. C., Kim, M., Chlebowski, R. T., Khandekar, J., Ko, M. G., McTiernan, A., Neuhouser, M. L., Parker, D. R., Shikany, J. M., Stefanick, M. L., Thomson, C. A., Rohan, T. E. 2009; 18 (7): 2046-2053

  Abstract

  The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure.

  View details for DOI 10.1158/1055-9965.EPI-09-0235

  View details for Web of Science ID 000268059700015

  View details for PubMedID 19567502

• Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Chlebowski, R. T., Schwartz, A., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Chien, J. W., Chen, C., Wactawski-Wende, J., Gass, M. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276607000022

• Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Chlebowski, R. T., Schwartz, A., Wakelee, H., Anderson, G. L., Stefanick, M. L., Manson, J. E., Chien, J. W., Chen, C., Wactawski-Wende, J., Gass, M. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606602097

• Calcium Plus Vitamin D Supplementation and Mortality in Postmenopausal Women: The Women's Health Initiative Calcium-Vitamin D Randomized Controlled Trial JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LaCroix, A. Z., Kotchen, J., Anderson, G., Brzyski, R., Cauley, J. A., Cummings, S. R., Gass, M., Johnson, K. C., Ko, M., Larson, J., Manson, J. E., Stefanick, M. L., Wactawski-Wende, J. 2009; 64 (5): 559-567

  Abstract

  Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality.

  View details for DOI 10.1093/gerona/glp006

  View details for Web of Science ID 000265095900007

  View details for PubMedID 19221190

• Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study 5th International Congress on Vegetarian Nutrition Pierce, J. P., Natarajan, L., Caan, B. J., Flatt, S. W., Kealey, S., Gold, E. B., Hajek, R. A., Newman, V. A., Rock, C. L., Pu, M., Saquib, N., Stefanick, M. L., Thomson, C. A., Parker, B. AMER SOC NUTRITION-ASN. 2009: S1565–S1571

  View details for DOI 10.3945/ajcn.2009.26736F

  View details for Web of Science ID 000265394300045

• Colorectal Cancer in Relation to Postmenopausal Estrogen and Estrogen Plus Progestin in the Women's Health Initiative Clinical Trial and Observational Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Prentice, R. L., Pettinger, M., Beresford, S. A., Wactawski-Wende, J., Hubbell, F. A., Stefanick, M. L., Chlebowski, R. T. 2009; 18 (5): 1531-1537

  Abstract

  Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants andPostmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review.Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period.Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.

  View details for DOI 10.1158/1055-9965.EPI-08-1209

  View details for Web of Science ID 000266081500027

  View details for PubMedID 19423530

• Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study. American journal of clinical nutrition Pierce, J. P., Natarajan, L., Caan, B. J., Flatt, S. W., Kealey, S., Gold, E. B., Hajek, R. A., Newman, V. A., Rock, C. L., Pu, M., Saquib, N., Stefanick, M. L., Thomson, C. A., Parker, B. 2009; 89 (5): 1565S-1571S

  Abstract

  A diet high in vegetables, fruit, and fiber and low in fat decreased additional risk of secondary breast cancer events in women without hot flashes (HF-) compared with that in women with hot flashes (HF+), possibly through lowered concentrations of circulating estrogens.The objective was to investigate the intervention effect by baseline quartiles of dietary pattern among breast cancer survivors in the HF- subgroup of the Women's Healthy Eating and Living Study. Design: A randomized controlled trial compared a putative cancer prevention diet with a diet of 5 servings of vegetables and fruit daily in early-stage breast cancer survivors. Participants did not experience hot flashes at baseline (n = 896). We confirmed cancer status for 96% of participants approximately 7.3 y after enrollment.The study intervention achieved a large between-group difference in dietary pattern that, at 4 y, was not significantly different across baseline quartiles of dietary pattern. The intervention group experienced fewer breast cancer events than did the comparison group for all of the baseline quartiles. This difference was significant only in upper baseline quartiles of intake of vegetables, fruit, and fiber and in the lowest quartile of fat. A significant trend for fewer breast cancer events was observed across quartiles of vegetable-fruit and fiber consumption.The secondary analysis showing the decreased risk in the HF- subgroup was not explained by amount of change in dietary pattern achieved. The difference was strongest in the quartile with the most putatively cancer-preventive dietary pattern at baseline.

  View details for DOI 10.3945/ajcn.2009.26736F

  View details for PubMedID 19339393

• Biomarker-calibrated Energy and Protein Consumption and Increased Cancer Risk Among Postmenopausal Women AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Shaw, P. A., Bingham, S. A., Beresford, S. A., Caan, B., Neuhouser, M. L., Patterson, R. E., Stefanick, M. L., Satterfield, S., Thomson, C. A., Snetselaar, L., Thomas, A., Tinker, L. F. 2009; 169 (8): 977-989

  Abstract

  The authors previously reported equations, derived from the Nutrient Biomarker Study within the Women's Health Initiative, that produce calibrated estimates of energy, protein, and percentage of energy from protein consumption from corresponding food frequency questionnaire estimates and data on other factors, such as body mass index, age, and ethnicity. Here, these equations were applied to yield calibrated consumption estimates for 21,711 women enrolled in the Women's Health Initiative dietary modification trial comparison group and 59,105 women enrolled in the observational study. These estimates were related prospectively to total and site-specific invasive cancer incidence (1993-2005). In combined cohort analyses that do not control for body mass, uncalibrated energy was not associated with total cancer incidence or site-specific cancer incidence for most sites, whereas biomarker-calibrated energy was positively associated with total cancer (hazard ratio = 1.18, 95% confidence interval: 1.10, 1.27, for 20% consumption increase), as well as with breast, colon, endometrial, and kidney cancer (respective hazard ratios of 1.24, 1.35, 1.83, and 1.47). Calibrated protein was weakly associated, and calibrated percentage of energy from protein was inversely associated, with total cancer. Calibrated energy and body mass index associations were highly interdependent. Implications for the interpretation of nutritional epidemiology studies are described.

  View details for DOI 10.1093/aje/kwp008

  View details for Web of Science ID 000264634900008

  View details for PubMedID 19258487

• Association Between Sleep Architecture and Measures of Body Composition SLEEP Rao, M. N., Blackwell, T., Susan, R., Stefanick, M. L., Ancoli-Israel, S., Stone, K. L. 2009; 32 (4): 483-490

  Abstract

  To determine whether slow wave sleep (SWS) is inversely associated with body mass index (BMI) and other measures of body composition.Cross-sectional, observational study.Community-based.2745 older men from the MrOS Sleep Study who completed polysomnography. Interventions: N/A.SWS as a percentage of total sleep duration was obtained from in-home, overnight polysomnography. Measures of body composition including BMI, weight, waist circumference and total body fat mass were determined by standard techniques. Other covariates in the analysis were age, race/ethnicity, clinic site, physical activity, respiratory disturbance index (RDI), total sleep time, and sleep efficiency. In the multivariate analysis, there was a significant inverse association between quartiles of SWS and BMI (P-trend = 0.0095). Older men in the lowest quartile of SWS had an average BMI of 27.4 kg/m2, compared to 26.8 for those in the highest quartile of SWS. This association was attenuated in men with RDI > or = 15. Furthermore, participants in the lowest quartile of SWS had a 1.4-fold increased odds for obesity (P = 0.03, 95% CI 1.0, 1.8) compared to those in the highest quartile. A similar inverse association between SWS and waist circumference as well as weight was observed. REM sleep was not associated with measures of body composition.Independent of sleep duration, percentage time in SWS is inversely associated with BMI and other measures of body composition in this population of older men. Participants in the lowest quartile of SWS (compared to those in the highest quartile) are at increased risk for obesity.

  View details for Web of Science ID 000264543300006

  View details for PubMedID 19413142

  View details for PubMedCentralID PMC2663862

• Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women NEW ENGLAND JOURNAL OF MEDICINE Chlebowski, R. T., Kuller, L. H., Prentice, R. L., Stefanick, M. L., Manson, J. E., Gass, M., Aragaki, A. K., Ockene, J. K., Lane, D. S., Sarto, G. E., Rajkovic, A., Schenken, R., Hendrix, S. L., Ravdin, P. M., Rohan, T. E., Yasmeen, S., Anderson, G. 2009; 360 (6): 573-587

  Abstract

  Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

  View details for Web of Science ID 000263028800004

  View details for PubMedID 19196674

• Longitudinal Biological Exposure to Carotenoids Is Associated with Breast Cancer-Free Survival in the Women's Healthy Eating and Living Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Rock, C. L., Natarajan, L., Pu, M., Thomson, C. A., Flatt, S. W., Caan, B. J., Gold, E. B., Al-Delaimy, W. K., Newman, V. A., Hajek, R. A., Stefanick, M. L., Pierce, J. P. 2009; 18 (2): 486-494

  Abstract

  In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer-free survival in the Women's Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.

  View details for DOI 10.1158/1055-9965.EPI-08-0809

  View details for Web of Science ID 000263547800016

  View details for PubMedID 19190138

• Dietary Pattern Influences Breast Cancer Prognosis in Women Without Hot Flashes: The Women's Healthy Eating and Living Trial JOURNAL OF CLINICAL ONCOLOGY Gold, E. B., Pierce, J. P., Natarajan, L., Stefanick, M. L., Laughlin, G. A., Caan, B. J., Flatt, S. W., Emond, J. A., Saquib, N., Madlensky, L., Kealey, S., Wasserman, L., Thomson, C. A., Rock, C. L., Parker, B. A., Karanja, N., Jones, V., Hajek, R. A., Pu, M., Mortimer, J. E. 2009; 27 (3): 352-359

  Abstract

  To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment.A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines.Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002).A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.

  View details for DOI 10.1200/JCO.2008.16.1067

  View details for Web of Science ID 000262499100007

  View details for PubMedID 19075284

• Breast cancer after stopping estrogen plus progestin in postmenopausal women in the women's health initiative. 31st Annual Meeting of the San Antonio Breast Cancer Symposium Chlebowski, R. T., Kuller, L., Anderson, G., Mason, J. A., Schenken, R., Rajkovic, A., Stefanick, M., Sarto, G., Ravdin, P., Prentice, R. AMER ASSOC CANCER RESEARCH. 2009: 78S–79S

  View details for Web of Science ID 000262583200057

• Postmenopausal hormone therapy and subclinical cerebrovascular disease The WHIMS-MRI Study NEUROLOGY Coker, L. H., Hogan, P. E., Bryan, N. R., Kuller, L. H., Margolis, K. L., Bettermann, K., Wallace, R. B., Lao, Z., Freeman, R., Stefanick, M. L., Shumaker, S. A. 2009; 72 (2): 125-134

  Abstract

  The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS.We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of alpha = 0.05 was used.In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo.Conjugated equine estrogen-based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials.

  View details for DOI 10.1212/01.wnl.0000339036.88842.9e

  View details for Web of Science ID 000262393200005

  View details for PubMedID 19139363

• Postmenopausal hormone therapy and regional brain volumes The WHIMS-MRI Study NEUROLOGY Resnick, S. M., Espeland, M. A., Jaramillo, S. A., Hirsch, C., Stefanick, M. L., Murray, A. M., Ockene, J., Davatzikos, C. 2009; 72 (2): 135-142

  Abstract

  To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90).Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

  View details for DOI 10.1212/01.wnl.0000339037.76336.cf

  View details for Web of Science ID 000262393200006

  View details for PubMedID 19139364

• The association between sleep duration and obesity in older adults INTERNATIONAL JOURNAL OF OBESITY Patel, S. R., Blackwell, T., Redline, S., Ancoli-Israel, S., Cauley, J. A., Hillier, T. A., Lewis, C. E., Orwoll, E. S., Stefanick, M. L., Taylor, B. C., Yaffe, K., Stone, K. L. 2008; 32 (12): 1825-1834

  Abstract

  Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67-96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70-99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.Compared to those sleeping an average of 7-8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m(2) (95% confidence interval (CI): 2.0-2.9) greater in men and 1.8 kg/m(2) (95% CI: 1.1-2.4) greater in women. The odds of obesity (BMI >or= 30 kg/m(2)) was 3.7-fold greater (95% CI: 2.7-5.0) in men and 2.3-fold greater in women (95% CI: 1.6-3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

  View details for DOI 10.1038/ijo.2008.198

  View details for Web of Science ID 000261695400009

  View details for PubMedID 18936766

• Sleep Duration and Risk of Ischemic Stroke in Postmenopausal Women STROKE Chen, J., Brunner, R. L., Ren, H., Wassertheil-Smoller, S., Larson, J. C., Levine, D. W., Allison, M., Naughton, M. J., Stefanick, M. L. 2008; 39 (12): 3185-3192

  Abstract

  Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed.We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics.At baseline, 8.3% of subjects had reported their sleep duration as or=9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting or=9 hours of sleep. A modestly stronger association with sleep duration or=9 hours/night) need further elucidation.

  View details for DOI 10.1161/STROKEAHA.108.521773

  View details for Web of Science ID 000261224800010

  View details for PubMedID 18635832

  View details for PubMedCentralID PMC2587518

• Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Chlebowski, R. T., Johnson, K. C., Kooperberg, C., Pettinger, M., Wactawski-Wende, J., Rohan, T., Rossouw, J., Lane, D., O'Sullivan, M. J., Yasmeen, S., Hiatt, R. A., Shikany, J. M., Vitolins, M., Khandekar, J., Hubbell, F. A. 2008; 100 (22): 1581-1591

  Abstract

  Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships.Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided.Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20).Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

  View details for DOI 10.1093/jnci/djn360

  View details for Web of Science ID 000261170000007

  View details for PubMedID 19001601

• Sax Differences In Peripheral Arterial Disease 81st Annual Scientific Session of the American-Heart-Association Rafie, A. H., Sims, T., Edwards, K. A., Phan, T., Stefanick, M. L., Assimes, T., Trammel, J. A., Olin, J., Cooke, J. P. LIPPINCOTT WILLIAMS & WILKINS. 2008: S811–S811

  View details for Web of Science ID 000262104502719

• Conjugated equine estrogens and colorectal cancer incidence and survival: The women's health initiative randomized clinical trial CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ritenbaugh, C., Stanford, J. L., Wu, L., Shikany, J. M., Schoen, R. E., Stefanick, M. L., Taylor, V., Garland, C., Frank, G., Lane, D., Mason, E., Mcneeley, S. G., Ascensao, J., Chlebowski, R. T. 2008; 17 (10): 2609-2618

  Abstract

  In separate Women's Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial.10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected.After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19).In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis.

  View details for DOI 10.1158/1055-9965.EPI-08-0385

  View details for Web of Science ID 000260051000013

  View details for PubMedID 18829444

  View details for PubMedCentralID PMC2937217

• Hip bone density predicts breast cancer risk independently of gail score - Results from the women's health initiative CANCER Chen, Z., Arendell, L., Aickin, M., Cauley, J., Lewis, C. E., Chlebowski, R., Nabel, E., Rossouw, J., Ludlam, S., Pottern, L., McGowan, J., Ford, L., Geller, N., Prentice, R., Anderson, G., LaCroix, A., Kooperberg, C. L., Patterson, R. E., McTiernan, A., Shumaker, S., Stein, E., Cummings, S., Wassertheil-Smoller, S., Hays, J., Manson, J., Assaf, A. R., Phillips, L., Beresford, S., Hsia, J., Chlebowski, R., Whitlock, E., Caan, B., Howard, B. V., Van Horn, L., Black, H., Stefanick, M. L., Lane, D., Jackson, R., Lewis, C. E., Bassford, T., Wactawski-Wende, J., Robbins, J., Hubbell, F. A., Judd, H., Langer, R. D., Gass, M., Limacher, M., Curb, D., Wallace, R., Ockene, J., Lasser, N., O'Sullivan, M. J., Margolis, K., Brunner, R., Heiss, G., Kuller, L., Johnson, K. C., Brzyski, R., Santo, G. E., Bonds, D., Henddx, S., Kotchen, J. M. 2008; 113 (5): 907-915

  Abstract

  The Gail model has been commonly used to estimate a woman's risk of breast cancer within a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it appears to play no role in the Gail model. The objective of the current study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score.In this prospective study, 9941 postmenopausal women who had a baseline hip BMD and Gail score from the Women's Health Initiative were included in the analysis. Their average age was 63.0 +/- 7.4 years at baseline.After an average of 8.43 years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazards ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (>or=1.67%) and 1.25 (95% CI, 1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting the analysis to women with both BMD and a Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (P < .05).The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population was found to be independent of the Gail score. However, among women with both high BMD and a high Gail score, there appears to be an interaction between these 2 factors. These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer.

  View details for DOI 10.1002/cncr.23674

  View details for Web of Science ID 000259069000007

  View details for PubMedID 18666209

• Conjugated equine estrogens and breast cancer risk in the women's health initiative clinical trial and observational study AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Chlebowski, R. T., Stefanick, M. L., Manson, J. E., Langer, R. D., Pettinger, M., Hendrix, S. L., Hubbell, F. A., Kooperberg, C., Kuller, L. H., Lane, D. S., McTiernan, A., O'Sullivan, M. J., Rossouw, J. E., Anderson, G. L. 2008; 167 (12): 1407-1415

  Abstract

  The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

  View details for DOI 10.1093/aje/kwn090

  View details for Web of Science ID 000256755900002

  View details for PubMedID 18448442

• Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events AMERICAN JOURNAL OF CARDIOLOGY Bray, P. F., Larson, J. C., LaCroix, A. Z., Manson, J., Limacher, M. C., Rossouw, J. E., Lasser, N. L., Lawson, W. E., Stefanick, M. L., Langer, R. D., Margolis, K. L. 2008; 101 (11): 1599-1605

  Abstract

  Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.

  View details for DOI 10.1016/j.amjcard.2008.01.043

  View details for Web of Science ID 000256450700011

  View details for PubMedID 18489937

• Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women's Health Initiative AMERICAN JOURNAL OF EPIDEMIOLOGY Neuhouser, M. L., Tinker, L., Shaw, P. A., Schoeller, D., Bingham, S. A., Van Horn, L., Beresford, S. A., Caan, B., Thomson, C., Satterfield, S., Kuller, L., Heiss, G., Smit, E., Sarto, G., Ockene, J., Stefanick, M. L., Assaf, A., Runswick, S., Prentice, R. L. 2008; 167 (10): 1247-1259

  Abstract

  Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Women's Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.

  View details for DOI 10.1093/aje/kwn026

  View details for Web of Science ID 000255756100013

  View details for PubMedID 18344516

• Estrogen plus progestin therapy and breast cancer in recently postmenopausal women AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Chlebowski, R. T., Stefanick, M. L., Manson, J. E., Pettinger, M., Hendrix, S. L., Hubbell, F. A., Kooperberg, C., Kuller, L. H., Lane, D. S., McTiernan, A., O'Sullivan, M. J., Rossouw, J. E., Anderson, G. L. 2008; 167 (10): 1207-1216

  Abstract

  The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.

  View details for DOI 10.1093/aje/kwn044

  View details for Web of Science ID 000255756100009

  View details for PubMedID 18372396

• Grip strength predicts dementia in 75 to 80 year-old women: The Women's Health Initiative Memory Study (WHIMS) Annual Meeting of the American-Geriatrics-Society Atkinson, H. H., Williamson, J. D., Rapp, S. R., Lovato, J., Sink, K. M., Absher, J. R., Gass, M., Henderson, V., Johnson, K. C., Kostis, J. B., Mouton, C., Ockene, J. K., Stefanick, M. L., Lane, D. S., Espeland, M. A. WILEY-BLACKWELL. 2008: S107–S107

  View details for Web of Science ID 000254840300311

• Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Heiss, G., Wallace, R., Anderson, G. L., Aragaki, A., Beresford, S. A., Brzyski, R., Chlebowski, R. T., Gass, M., LaCroix, A., Manson, J. E., Prentice, R. L., Rossouw, J., Stefanick, M. L. 2008; 299 (9): 1036-1045

  Abstract

  The Women's Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits.To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women.Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention.The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo.clinicaltrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000253644800021

  View details for PubMedID 18319414

• Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Rock, C. L., Flatt, S. W., Laughlin, G. A., Gold, E. B., Thomson, C. A., Natarajan, L., Jones, L. A., Caan, B. J., Stefanick, M. L., Hajek, R. A., Al-Delaimyl, W. K., Stanczyk, F. Z., Pierce, J. P. 2008; 17 (3): 614-620

  Abstract

  Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.

  View details for DOI 10.1158/1055-9965.EPI-07-0761

  View details for Web of Science ID 000254373600020

  View details for PubMedID 18323413

• Factors associated with 5-year risk of hip fracture in postmenopausal women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Robbins, J., Aragaki, A. K., Kooperberg, C., Watts, N., Wactawski-Wende, J., Jackson, R. D., LeBoff, M. S., Lewis, C. E., Chen, Z., Stefanick, M. L., Cauley, J. 2007; 298 (20): 2389-2398

  Abstract

  The 329,000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention.To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women.A total of 93,676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68,132 women who participated in the clinical trial. The model was tested in a subset of 10,750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment.The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves.During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%).This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.

  View details for Web of Science ID 000251163400019

  View details for PubMedID 18042916

• Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern JOURNAL OF NUTRITION Pierce, J. P., Newman, V. A., Natarajan, L., Flatt, S. W., Al-Delaimy, W. K., Caan, B. J., Emond, J. A., Faerber, S., Gold, E. B., Hajek, R. A., Hollenbach, K., Jones, L. A., Karanja, N., Kcaley, S., Madlensky, L., Marshall, J., Ritenbaugh, C., Rock, C. L., Stefanick, M. L., Thomson, C., Wasserman, L., Parker, B. A. 2007; 137 (10): 2291-2296

  Abstract

  Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.

  View details for Web of Science ID 000249701400020

  View details for PubMedID 17885013

• Prevalence and correlates of sleep-disordered breathing in older men: Osteoporotic fractures in men sleep study 72nd Annual International Scientific Assembly of the American-College-of-Chest-Physicians Mehra, R., Stone, K. L., Blackwell, T., Israel, S. A., Dam, T. L., Stefanick, M. L., Redline, S. BLACKWELL PUBLISHING. 2007: 1356–64

  Abstract

  To determine the prevalence and distribution of sleep-disordered breathing and associated correlates in a large cohort of older men using several standardized definitions.Cross-sectional analyses.Six U.S. communities.Polysomnography was performed on 2,911 participants of the Outcomes of Sleep Disorders in Older Men Sleep Study (mean age+/-standard deviation 76.38+/-5.53; body mass index 27.17+/-3.8 kg/m(2)).Three outcomes were assessed: sleep-disordered breathing (respiratory disturbance index > or =15), obstructive apnea (obstructive apnea index > or =5), and central apnea (central apnea index > or =5).The prevalence of moderate-severe sleep-disordered breathing was estimated to be 21.4% to 26.4%. Multivariable logistic regression models demonstrated that age (adjusted odds ratio (AOR) per 5-year increase =1.24, 95% confidence interval (CI)=1.15-1.34), obesity (AOR=2.54, 95% CI=2.09-3.09), Asian versus Caucasian race (AOR=2.14, 95% CI=1.33-3.45), snoring (AOR=2.01, 95% CI=1.62-2.49), sleepiness (AOR=1.41, 95% CI=1.11-1.79), hypertension (AOR=1.26, 95% CI=1.06-1.50), cardiovascular disease (AOR=1.24, 95% CI=1.19-1.29), and heart failure (AOR=1.81, 1.31-2.51) were independently associated with sleep-disordered breathing; snoring (AOR=2.10, 95% CI=1.67-2.70), age (AOR per 5-year increase=1.27, 95% CI=1.18-1.38), obesity (AOR=1.48, 95% CI=1.21-1.82), and heart failure (AOR=1.60, 95% CI=1.15-2.24) were associated with obstructive apnea; and age (AOR=1.33, 1.17-1.50) and heart failure (AOR=1.88, 95% CI=1.17-3.04) were associated with central apnea.Regardless of definition, a high prevalence of sleep disorders is observed in community-dwelling older men. Qualitatively similar associations were observed between sleep disorders and snoring, obesity, and comorbidities, as reported for middle aged populations. Asian race was associated with sleep-disordered breathing.

  View details for DOI 10.1111/j.1532-5415.2007.01290.x

  View details for Web of Science ID 000249178400005

  View details for PubMedID 17767677

• Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer - The Women's Healthy Eating and Living (WHEL) Randomized Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pierce, J. P., Natarajan, L., Caan, B. J., Parker, B. A., Greenberg, E. R., Flatt, S. W., Rock, C. L., Kealey, S., Al-Delaimy, W. K., Bardwell, W. A., Carlson, R. W., Emond, J. A., Faerber, S., Gold, E. B., Hajek, R. A., Hollenbach, K., Jones, L. A., Karanja, N., Madlensky, L., Marshall, J., Newman, V. A., Ritenbaugh, C., Thomson, C. A., Wasserman, L., Stefanick, M. L. 2007; 298 (3): 289-298

  Abstract

  Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the "5-A-Day" dietary guidelines.Invasive breast cancer event (recurrence or new primary) or death from any cause.From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.clinicaltrials.gov Identifier: NCT00003787.

  View details for Web of Science ID 000248086700023

  View details for PubMedID 17635889

• Estrogen therapy and coronary-artery calcification NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Allison, M. A., Rossouw, J. E., Carr, J. J., Langer, R. D., Hsia, J., Kuller, L. H., Cochrane, B. B., Hunt, J. R., Ludlam, S. E., Pettinger, M. B., Gass, M., Margolis, K. L., Nathan, L., Ockene, J. K., Prentice, R. L., Robbins, J., Stefanick, M. L., Rossouw, J. E., Ludlam, S., Cochrane, B. B., Hunt, J. R., Lund, B., Prentice, R., Carr, J. J., O'Rourke, C., Du, L., Pillsbury, S., Hightower, C., Ellison, R., Tan, J., Wassertheil-Smoller, S., Magnani, M., Noble, D. H., Dellicarpini, T., Manson, J. E., Bueche, M., McGinnis, A. D., Rybicki, F. J., Assaf, A. R., Sloane, G., Phillips, L. S., Butler, V., Huber, M., Vitali, J., Hsia, J., Lebrun, C., Palm, R., Embersit, D., Whitlock, E., Arnold, K., Sidney, S., Cantrell, V., Kotchen, J. M., Feltz, C., Howard, B. V., Thomas-Geevarghese, A., Boggs, G., Jelinick, J. S., Greenland, P., Neuman, A., Carlson-Lund, G., Giovanazzi, S. M., Stefanick, M. L., Swope, S., Jackson, R., Toussant, K., Lewis, C. E., Pierce, P., Stallings, C., Wactawski-Wende, J., Goel, S., Laughlin, R., Robbins, J., Zaragoza, S., Macias, D., BeLisle, D., Nathan, L., Voigt, B., Goldin, J., Woo, M., Langer, R. D., Allison, M. A., Lien, X., Wright, C. M., Gass, M., Sheridan, S., Robinson, J. G., Feddersen, D., Kelly-Brake, K., Carroll, J., Ockene, J., Churchill, L., Lasser, N. L., Miller, B., Maldjian, P. D., Pierre-Louis, J., FISHMAN, J., O'Sullivan, M. J., Fernandez, D., Margolis, K. L., Bjerk, C. L., Truwit, C., Hearity, J. A., Hyslop, W. B., Darroch, K., Murphy, C., Heiss, G., Kuller, L. H., Edmundowicz, D., Ives, D., Johnson, K. C., Satterfield, S., Connelly, S. A., Jones, E. L., Brzyski, R., Nashawati, M. A., Torchia, S., Rodriguez, A., Garza, R., Nentwich, P., Sarto, G. E., Broderick, L., Sweitzer, N. K., Nabel, E., Rossouw, J. E., Ludlam, S. E., Pottern, L., McGowan, J., Ford, L., Geller, N., Prentice, R. L., Anderson, G., Lacroix, A., Kooperberg, C. L., Patterson, R. E., McTiernan, A., Shumaker, S., Stein, E., Cummings, S., Wassertheil-Smoller, S., Hays, J., Manson, J. E., Assaf, A. R., Phillips, L., Beresford, S., Hsia, J., Chlebowski, R., Whitlock, E., Caan, B., Kotchen, J. M., Howard, B. V., Van Horn, L., BLACK, H., Stefanick, M. L., Lane, D., Jackson, R., Lewis, C. E., Bassford, T., Wactawski-Wende, J., Robbins, J., Hubbell, F. A., Judd, H., Langer, R. D., Gass, M., Limacher, M., Curb, D., Wallace, R., Ockene, J., Lasser, N., O'Sullivan, M. J., Margolis, K. L., Brunner, R., Heiss, G., Kuller, L. H., Johnson, K. C., Brzyski, R., Sarto, G. E., Bonds, D., Hendrix, S. 2007; 356 (25): 2591-2602

  Abstract

  Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.)

  View details for Web of Science ID 000247351200006

  View details for PubMedID 17582069

• Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity JOURNAL OF CLINICAL ONCOLOGY Pierce, J. P., Stefanick, M. L., Flatt, S. W., Natarajan, L., Sternfeld, B., Madlensky, L., Al-Delaimy, W. K., Thomson, C. A., Kealey, S., Hajek, R., Parker, B. A., Newman, V. A., Caan, B., Rock, C. L. 2007; 25 (17): 2345-2351

  Abstract

  Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables.A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005.In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor-positive cancers.A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.

  View details for DOI 10.1200/JCO.2006.08.6819

  View details for Web of Science ID 000247241600005

  View details for PubMedID 17557947

• Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rossouw, J. E., Prentice, R. L., Manson, J. E., Wu, L., Barad, D., Barnabei, V. M., Ko, M., LaCroix, A. Z., Margolis, K. L., Stefanick, M. L. 2007; 297 (13): 1465-1477

  Abstract

  The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.clinicaltrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000245404100023

  View details for PubMedID 17405972

• Objective measures of sleep duration and obesity in older men and women 21st Annual Meeting of the American-Professional-Sleep-Societies Stone, K., Blackwell, T., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Orwoll, E., Cauley, J., Lewis, C., Redline, S. AMER ACAD SLEEP MEDICINE. 2007: A106–A107

  View details for Web of Science ID 000246224900313

• The relationship of actigraphic sleep characteristics and measures of cognition: The mros sleep study 21st Annual Meeting of the American-Professional-Sleep-Societies Blackwell, T., Yaffe, K., Redline, S., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Stone, K. AMER ACAD SLEEP MEDICINE. 2007: A111–A111

  View details for Web of Science ID 000246224900325

• The relationship of sleep disordered breathing and cognition: The mros sleep study 21st Annual Meeting of the American-Professional-Sleep-Societies Stone, K., Blackwell, T., Yaffe, K., Ancoli-Israel, S., Ensrud, K., Stefanick, M., Redline, S. AMER ACAD SLEEP MEDICINE. 2007: A105–A105

  View details for Web of Science ID 000246224900308

• Does calcium supplementation increase cardiovascular risk: The women's health initiative randomized trial 79th Annual Scientific Session of the American-Heart-Association Hsia, J., Heiss, G., Ren, H., Trevisan, M., Greenland, P., Johnson, K., Allison, M., Stefanick, M., Manson, J., Heckbert, S., Dolan, N., Sidney, S., Permanente, K. LIPPINCOTT WILLIAMS & WILKINS. 2006: 884–84

  View details for Web of Science ID 000241792805571

• Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer BREAST CANCER RESEARCH AND TREATMENT Caan, B. J., Emond, J. A., Natarajan, L., Castillo, A., Gunderson, E. P., Habel, L., Jones, L., Newman, V. A., Rock, C. L., Slattery, M. L., Stefanick, M. L., Sternfeld, B., Thomson, C. A., Pierce, J. P. 2006; 99 (1): 47-57

  Abstract

  To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence.Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors.Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis).Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.

  View details for DOI 10.1007/s10549-006-9179-y

  View details for Web of Science ID 000239548500006

  View details for PubMedID 16541317

• Risk factors for hip fracture, WHI. 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research Robbins, J., Agaki, A., Kooperberg, C., Cauley, J. A., Chen, Z., Wactawski-Wende, J., LeBoff, M. S., Lewis, C. E., Jackson, R., Watts, N. B., Stefanick, M. WILEY-BLACKWELL. 2006: S55–S55

  View details for Web of Science ID 000240866300206

• Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study OSTEOPOROSIS INTERNATIONAL Ensrud, K. E., Lewis, C. E., Lambert, L. C., Taylor, B. C., Fink, H. A., Barrett-Connor, E., Cauley, J. A., Stefanick, M. L., Orwoll, E. 2006; 17 (9): 1329-1336

  Abstract

  Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones.To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study.Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001).These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

  View details for DOI 10.1007/s00198-006-0088-z

  View details for Web of Science ID 000239300400002

  View details for PubMedID 16767524

• Risk-benefit profiles of raloxifene for women NEW ENGLAND JOURNAL OF MEDICINE Stefanick, M. L. 2006; 355 (2): 190-192

  View details for Web of Science ID 000238970600013

  View details for PubMedID 16837684

• Mortality and cardiac and vascular outcomes in extremely obese women JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION McTigue, K., Larson, J. C., Valoski, A., Burke, G., Kotchen, J., Lewis, C. E., Stefanick, M. L., Van Horn, L., Kuller, L. 2006; 296 (1): 79-86

  Abstract

  Obesity, typically measured as body mass index of 30 or higher, has 3 subclasses: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (> or =40). Extreme obesity is increasing particularly rapidly in the United States, yet its health risks are not well characterized.To determine how cardiovascular and mortality risks differ across clinical weight categories in women, with a focus on extreme obesity.We examined incident mortality and cardiovascular outcomes by weight status in 90,185 women recruited from 40 US centers for the Women's Health Initiative Observational Study and followed up for an average of 7.0 years (October 1, 1993 to August 31, 2004).Incidence of mortality, coronary heart disease, diabetes, and hypertension.Extreme obesity prevalence differed with race/ethnicity, from 1% among Asian and Pacific Islanders to 10% among black women. All-cause mortality rates per 10,000 person-years were 68.39 (95% confidence interval [CI], 65.26-71.68) for normal body mass index, 71.16 (95% CI, 67.68-74.82) for overweight, 84.47 (95% CI, 78.90-90.42) for obesity 1, 102.85 (95% CI, 92.90-113.86) for obesity 2, and 116.85 (95% CI, 103.36-132.11) for extreme obesity. Analyses adjusted for age, smoking, educational achievement, US region, and physical activity levels showed that weight-related risk for all-cause mortality, coronary heart disease mortality, and coronary heart disease incidence did not differ by race/ethnicity. Adjusted analyses among white and black participants showed positive trends in all-cause mortality and coronary heart disease incidence with increasing weight category. Much of the obesity-related mortality and coronary heart disease risk was mediated by diabetes, hypertension, and hyperlipidemia. In white women, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women.Considering obesity as a body mass index of 30 or higher may lead to misinterpretation of individual and population risks. Escalating extreme obesity may exacerbate health effects and costs of the obesity epidemic.

  View details for Web of Science ID 000238683100025

  View details for PubMedID 16820550

• Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Gold, E. B., Flatt, S. W., Pierce, J. P., Bardwell, W. A., Hajek, R. A., Newman, V. A., Rock, C. L., Stefanick, M. L. 2006; 13 (3): 423-433

  Abstract

  Vasomotor symptoms (VMS)(hot flashes, night sweats) are associated with natural or surgically or chemotherapy-induced menopause, the latter occurring frequently in women treated for breast cancer. To manage VMS, some women seek alternatives to menopausal hormone therapy, such as supplements or modified food choices. The objective of the present analyses was to assess associations of VMS occurrence and change in severity of VMS over 12 months with dietary intakes of fiber, fat, and selected soy-containing foods, and use of phytoestrogen or vitamin E supplements in women with recent early stage breast cancer, adjusting for covariates.Using multivariate logistic regression, data were analyzed from 2,198 women with early-stage breast cancer who enrolled 2 to 48 months after diagnosis in the Women's Healthy Eating and Living randomized, controlled trial of a high-vegetable, high-fiber, reduced-fat diet.Being peri- or postmenopausal, using tamoxifen, having low social support or depressive symptoms, and using vitamin E or phytoestrogen supplements were significantly associated cross-sectionally with reporting moderate/severe VMS at enrollment. Increased symptom severity after 12 months was significantly associated with higher body mass index, tamoxifen use, and smoking. Decreased symptom severity at 12 months was significantly associated with high dietary fiber intake; no decrease was observed in women who were peri- or postmenopausal, using tamoxifen, or had low fat intake or low social support.High dietary fiber intakes, premenopausal, and high social support were related to decreased severity of VMS 1 year after study enrollment in women recently treated for breast cancer.

  View details for DOI 10.1097/01.gme.0000185754.85328.44

  View details for Web of Science ID 000238116100013

  View details for PubMedID 16735939

• Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stefanick, M. L., Anderson, G. L., Margolis, K. L., Hendrix, S. L., Rodabough, R. J., Paskett, E. D., Lane, D. S., Hubbell, F. A., Assaf, A. R., Sarto, G. E., Schenken, R. S., Yasmeen, S., Lessin, L., Chlebowski, R. T. 2006; 295 (14): 1647-1657

  Abstract

  The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis.To determine the effects of CEE on breast cancers and mammographic findings.Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included.A dose of 0.625 mg/d of CEE or an identical-appearing placebo.Breast cancer incidence, tumor characteristics, and mammogram findings.After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up.Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits.clinicaltrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000236707300020

  View details for PubMedID 16609086

• Combined analysis of Women's Health Initiative Observational and Clinical Trial data on postmenopausal hormone treatment and cardiovascular disease AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Langer, R. D., Stefanick, M. L., Howard, B. V., Pettinger, M., Anderson, G. L., Barad, D., Curb, J. D., Kotchen, J., Kuller, L., Limacher, M., Wactawski-Wende, J. 2006; 163 (7): 589-599

  Abstract

  Circumstances in which both randomized controlled trial and observational study data are available provide an important opportunity to identify biases and improve study design and analysis procedures. In addition, joint analyses of data from the two sources can extend clinical trial findings. The US Women's Health Initiative includes randomized controlled trials of use of estrogen by posthysterectomy women and of estrogen plus progestin by women with a uterus, along with corresponding observational study components. In this paper, for coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin. These findings support certain combined analyses of the observational data on estrogen and the estrogen plus progestin clinical trial and observational study data to give adjusted observational study estimates of estrogen treatment effects. The resulting treatment effect estimates are compared with corresponding clinical trial estimates, and parallel analyses are also presented for estrogen plus progestin. An application to postmenopausal hormone treatment effects on coronary heart disease among younger women is also provided.

  View details for DOI 10.1093/aje/kwj079

  View details for Web of Science ID 000236250900001

  View details for PubMedID 16484450

• Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancer INTERNATIONAL JOURNAL OF CANCER Modugno, F., Kip, K. E., Cochrane, B., Kuller, L., Klug, T. L., Rohan, T. E., Chlebowski, R. T., Lasser, N., Stefanick, M. L. 2006; 118 (5): 1292-1301

  Abstract

  Hormone therapy (HT) and body mass index (BMI) have been associated with postmenopausal breast cancer. Because estrogen metabolism may affect breast cancer risk and can be altered by weight and HT, it might play a role in the HT-BMI-breast cancer associations. We undertook a nested case-control study within the Observational Study of the Women's Health Initiative. Baseline levels of 2- and 16alpha-hydroxy estrone (2-OHE1 and 16alpha-OHE1) were measured in 200 women who developed breast cancer during follow-up and 200 healthy controls matched to cases by ethnicity, enrollment date, clinic site, type of HT and years since menopause. Wilcoxon nonparametric tests were used to compare estrogen metabolite levels between cases and controls. Conditional logistic regression was used to assess the relationship between BMI, estrogen metabolites and breast cancer risk. 16alpha-OHE1 levels were modestly but significantly higher in HT users among cases (median 356 pg/ml vs. 315 pg/ml) and controls (354 pg/ml vs. 298 pg/ml). 2-OHE1 levels were substantially and significantly higher in HT users among cases (369 pg/ml vs. 125 pg/ml) and controls (347 pg/ml vs. 134 pg/ml). For non-HT users only, greater BMI and higher 16alpha-OHE1 levels were individually and jointly associated with increased breast cancer risk (OR for women with high BMI and high 16alpha-OHE1 compared to those with low BMI and low 16alpha-OHE1 = 3.51, 95% CI = 1.34-9.16). No associations between BMI, estrogen metabolism and breast cancer risk were found for HT users. Estrogen metabolism differs according to both BMI and HT use, potentially explaining the interaction between BMI and HT in relation to breast cancer risk.

  View details for DOI 10.1002/ijc.21487

  View details for Web of Science ID 000235056100029

  View details for PubMedID 16161054

• Calcium plus vitamin D supplementation and the risk of colorectal cancer NEW ENGLAND JOURNAL OF MEDICINE Wactawski-Wende, J., Kotchen, J. M., Anderson, G. L., Assaf, A. R., Brunner, R. L., O'Sullivan, M. J., Margolis, K. L., Ockene, J. K., Phillips, L., Pottern, L., Prentice, R. L., Robbins, J., Rohan, T. E., Sarto, G. E., Sharma, S., Stefanick, M. L., Van Horn, L., Wallace, R. B., Whitlock, E., Bassford, T., Beresford, S. A., Black, H. R., Bonds, D. E., Brzyski, R. G., Caan, B., Chlebowski, R. T., Cochrane, B., Garland, C., Gass, M., Hays, J., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Jackson, R. D., Johnson, K. C., Judd, H., Kooperberg, C. L., Kuller, L. H., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lasser, N. L., Lewis, C. E., Limacher, M. C., Manson, J. E. 2006; 354 (7): 684-696

  Abstract

  Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

  View details for Web of Science ID 000235316100005

  View details for PubMedID 16481636

• Calcium plus vitamin D supplementation and the risk of fractures NEW ENGLAND JOURNAL OF MEDICINE Jackson, R. D., LaCroix, A. Z., Gass, M., Wallace, R. B., Robbins, J., Lewis, C. E., Bassford, T., Beresford, S. A., Black, H. R., Blanchette, P., Bonds, D. E., Brunner, R. L., Brzyski, R. G., Caan, B., Cauley, J. A., Chlebowski, R. T., Cummings, S. R., Granek, I., Hays, J., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Johnson, K. C., Judd, H., Kotchen, J. M., Kuller, L. H., Langer, R. D., Lasser, N. L., Limacher, M. C., Ludlam, S., Manson, J. E., Margolis, K. L., McGowan, J., Ockene, J. K., O'Sullivan, M. J., Phillips, L., Prentice, R. L., Sarto, G. E., Stefanick, M. L., Van Horn, L., Wactawski-Wende, J., Whitlock, E., Anderson, G. L., Assaf, A. R., Barad, D. 2006; 354 (7): 669-683

  Abstract

  The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

  View details for Web of Science ID 000235316100004

  View details for PubMedID 16481635

• Low-fat dietary pattern and risk of invasive breast cancer - The women's health initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Prentice, R. L., Caan, B., Chlebowski, R. T., Patterson, R., Kuller, L. H., Ockene, J. K., Margolis, K. L., Limacher, M. C., Manson, J. E., Parker, L. M., Paskett, E., Phillips, L., Robbins, J., Rossouw, J. E., Sarto, G. E., Shikany, J. M., Stefanick, M. L., Thomson, C. A., Van Horn, L., Vitolins, M. Z., Wactawski-Wende, J., Wallace, R. B., Wassertheil-Smoller, S., Whitlock, E., Yano, K., Adams-Campbell, L., Anderson, G. L., Assaf, A. R., Beresford, S. A., Black, H. R., Brunner, R. L., Brzyski, R. G., Ford, L., Gass, M., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Hsia, J., Hubbell, F. A., Jackson, R. D., Johnson, K. C., Kotchen, J. M., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lasser, N. L., Henderson, M. M. 2006; 295 (6): 629-642

  Abstract

  The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Invasive breast cancer incidence.Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.ClinicalTrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000235168200023

  View details for PubMedID 16467232

• Low-fat dietary pattern and risk of cardiovascular disease - The Women's Health Initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Howard, B. V., Van Horn, L., Hsia, J., Manson, J. E., Stefanick, M. L., Wassertheil-Smoller, S., Kuller, L. H., LaCroix, A. Z., Langer, R. D., Lasser, N. L., Lewis, C. E., Limacher, M. C., Margolis, K. L., Mysiw, J., Ockene, J. K., Parker, L. M., Perri, M. G., Phillips, L., Prentice, R. L., Robbins, J., Rossouw, J. E., Sarto, G. E., Schatz, I. J., Snetselaar, L. G., Stevens, V. J., Tinker, L. F., Trevisan, M., Vitolins, M. Z., Anderson, G. L., Assaf, A. R., Bassford, T., Beresford, S. A., Black, H. R., Brunner, R. L., Brzyski, R. G., Caan, B., Chlebowski, R. T., Gass, M., Granek, I., Greenland, P., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Hubbell, F. A., Johnson, K. C., Kotchen, J. M. 2006; 295 (6): 655-666

  Abstract

  Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.ClinicalTrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000235168200025

  View details for PubMedID 16467234

• Low-fat dietary pattern and risk of colorectal cancer - The Women's Health Initiative randomized controlled dietary modification trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Beresford, S. A., Johnson, K. C., Ritenbaugh, C., Lasser, N. L., Snetselaar, L. G., Black, H. R., Anderson, G. L., Assaf, A. R., Bassford, T., Bowen, D., Brunner, R. L., Brzyski, R. G., Caan, B., Chlebowski, R. T., Gass, M., Harrigan, R. C., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Howard, B. V., Hsia, J., Hubbell, F. A., Jackson, R. D., Kotchen, J. M., Kuller, L. H., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lewis, C. E., Manson, J. E., Margolis, K. L., Mossavar-Rahmani, Y., Ockene, J. K., Parker, L. M., Perri, M. G., Phillips, L., Prentice, R. L., Robbins, J., Rossouw, J. E., Sarto, G. E., Stefanick, M. L., Van Horn, L., Vitolins, M. Z., Wactawski-Wende, J., Wallace, R. B., Whitlock, E. 2006; 295 (6): 643-654

  Abstract

  Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Invasive colorectal cancer incidence.A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.ClinicalTrials.gov Identifier: NCT00000611.

  View details for Web of Science ID 000235168200024

  View details for PubMedID 16467233

• Low-fat dietary pattern and weight change over 7 years - The Women's Health Initiative Dietary Modification Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Howard, B. V., Manson, J. E., Stefanick, M. L., Beresford, S. A., Frank, G., Jones, B. T., Rodabough, R. J., Snetselaar, L., Thomson, C., Tinker, L., Vitolins, M., Prentice, R. 2006; 295 (1): 39-49

  Abstract

  Obesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets.To report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components.Randomized intervention trial of 48,835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women's Health Initiative Dietary Modification Trial; 40% (19,541) were randomized to the intervention and 60% (29,294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004).The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials.Change in body weight from baseline to follow-up.Women in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber.A low-fat eating pattern does not result in weight gain in postmenopausal women. Clinical Trial Registration ClinicalTrials.gov, NCT00000611.

  View details for Web of Science ID 000234381100019

  View details for PubMedID 16391215

• Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. American journal of medicine Stefanick, M. L. 2005; 118: 64-73

  Abstract

  The US Food and Drug Administration (FDA) approved marketing of diethylstilbestrol in 1941 and conjugated equine estrogens (CEE) in 1942 for treatment of menopausal symptoms. Estrogen sales doubled and tripled in the mid-1960s to mid-1970s, until 1975, when reports of increased endometrial cancer in estrogen users resulted in a dramatic decline. Estrogen use increased again, with evidence of protective effects of progestins on estrogen-induced endometrial changes, combined with a 1982 report that Premarin (conjugated estrogen tablets; Wyeth Pharmaceuticals, Philadelphia, PA) retained bone mass and a 1984 National Institutes of Health (NIH) Consensus Conference on Osteoporosis statement that estrogens were the most effective means for preventing bone loss. Despite conflicting reports in 1985 regarding the relation between estrogens and coronary heart disease (CHD), many published observations of reduced CHD risk in estrogen users--reinforced by clinical trial findings in 1995 of favorable lipoprotein changes in women assigned to CEE with or without a progestin--promoted increased use through the 1990s. By 2001, approximately 15 million US women were using estrogen therapy, with or without progestins. The 2002 Women's Health Initiative (WHI) report of greater harm than benefit of combined CEE plus a progestin resulted in a precipitous decrease in estrogen and progestin use and a serious reevaluation of menopausal hormone therapy, as well as increased interest in alternative approaches to managing menopausal symptoms, including use of "bioidentical" hormones. FDA guidelines regarding treatment indications for vasomotor symptoms, vaginal atrophy, and osteoporosis prevention have resulted in approval of several estrogen (and progestin) formulations, doses, and routes of administration, thereby providing many options for women who seek conventional therapy.

  View details for PubMedID 16414329

• Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study - A large observational study of the determinants of fracture in older men CONTEMPORARY CLINICAL TRIALS Orwoll, E., Blank, J. B., Barrett-Connor, E., Cauley, J., Cummings, S., Ensrud, K., Lewis, C., Cawthon, P. M., Marcus, R., Marshall, L. M., McGowan, J., Phipps, K., Sherman, S., Stefanick, M. L., Stone, K. 2005; 26 (5): 569-585

  Abstract

  Very little information is available to direct the prevention or management of osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a prospective cohort study designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in men. The study is also designed to understand how osteoporosis is related to prostate disease. At baseline, participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine, and DNA specimens were collected. After the baseline assessments, a questionnaire is mailed to participants every 4 months to ascertain incident falls, fractures, prostate cancer, and deaths. After an average of 4.5 years, participants are scheduled to return for a second comprehensive visit. Men were eligible if > or =65 years. 5995 men enrolled with a mean (+/-SD) age of 73.7 (+/-5.9) years, 11% of which were minorities. Most rated their health as good/excellent. Few were current smokers, although 59% had smoked previously, and 35% reported no alcohol intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass index was 26.9 kg/m2 (17-56). A non-traumatic fracture after age 50 was reported by 17% of the cohort. The MrOS cohort should provide valuable information concerning the determinants of fracture in men and should help set the stage for the development of effective methods to identify those at risk.

  View details for DOI 10.1016/j.cct.2005.05.006

  View details for Web of Science ID 000232023400007

  View details for PubMedID 16084776

• Postmenopausal hormone therapy and body composition - a substudy of the estrogen plus progestin trial of the Women's Health Initiative AMERICAN JOURNAL OF CLINICAL NUTRITION Chen, Z., Bassford, T., Green, S. B., Cauley, J. A., Jackson, R. D., LaCroix, A. Z., LeBoff, M., Stefanick, M. L., Margolis, K. L. 2005; 82 (3): 651-656

  Abstract

  It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women.This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women.The substudy was composed of 835 women from the estrogen plus progestin trial of the Women's Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed.After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (-0.04 kg) than did the women who received placebo (-0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: -0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took > or = 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis.A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.

  View details for Web of Science ID 000231809900024

  View details for PubMedID 16155280

• Combined postmenopausal hormone therapy and cardiovascular disease: Toward resolving the discrepancy between observational studies and the women's health initiative clinical trial AMERICAN JOURNAL OF EPIDEMIOLOGY Prentice, R. L., Langer, R., Stefanick, M. L., Howard, B. V., Pettinger, M., Anderson, G., Barad, D., Curb, J. D., Kotchen, J., Kuller, L., Limacher, M., Wactawski-Wende, J. 2005; 162 (5): 404-414

  Abstract

  Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.

  View details for DOI 10.1093/aje/kwi223

  View details for Web of Science ID 000231363800002

  View details for PubMedID 16033876

• Incident mortality, cardiac and vascular outcomes among extremely obese US women: A growing health threat 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention McTigue, K. M., Valoski, A., Chang, Y. F., Burke, G. L., Lewis, C. E., Kotchen, J., Stefanick, M. L., Van Horn, L., Kuller, L. H. LIPPINCOTT WILLIAMS & WILKINS. 2005: E204–E204

  View details for Web of Science ID 000228280900120

• Voluntary weight reduction in older men increases hip bone loss: The Osteoporotic Fractures in Men study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ensrud, K. E., Fullman, R. L., Barrett-Connor, E., Cauley, J. A., Stefanick, M. L., Fink, H. A., Lewis, C. E., Orwoll, E. 2005; 90 (4): 1998-2004

  Abstract

  To test the hypothesis that weight loss in older men is associated with increased rates of hip bone loss regardless of adiposity and intention to lose weight, we measured body weight, body composition, hip bone mineral density (BMD), and intention to lose weight in a cohort of 1342 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study and followed them prospectively for an average of 1.8 yr for changes in weight and BMD. The adjusted average rate of change in total hip BMD was 0.1%/yr in men with weight gain, -0.3%/yr in men with stable weight, and -1.4%/yr in men with weight loss (test for trend, P < 0.001). Higher rates of hip bone loss were observed in men with weight loss regardless of category of body mass index, body composition, or intention to lose weight. Even among obese (body mass index, > or =30 kg/m2) men trying to lose weight, those with documented voluntary weight reduction experienced an increase in hip bone loss (average rate of change in total hip BMD, 0.5%/yr in those with weight gain, -0.1%/yr in those with stable weight, and -1.7%/yr in those with weight loss; test for trend, P < 0.001). Older men who experience weight loss have increased rates of hip bone loss, even among overweight and obese men undergoing voluntary weight reduction.

  View details for DOI 10.1210/jc.2004-1805

  View details for Web of Science ID 000228198900014

  View details for PubMedID 15671096

• Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy - The Women's Health Initiative Observational Study CIRCULATION Howard, B. V., Kuller, L., Langer, R., Manson, J. E., Allen, C., Assaf, A., Cochrane, B. B., Larson, J. C., Lasser, N., Rainford, M., Van Horn, L., Stefanick, M. L., Trevisan, M. 2005; 111 (12): 1462-1470

  Abstract

  Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy.This analysis was conducted on 89 914 women in the Women's Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant.Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.

  View details for DOI 10.1161/01.CIR.0000159344.21672.FD

  View details for Web of Science ID 000227984800003

  View details for PubMedID 15781742

• Association between reported alcohol intake and cognition: Results from the Women's Health Initiative Memory Study AMERICAN JOURNAL OF EPIDEMIOLOGY Espeland, M. A., Gu, L., Masaki, K. H., Langer, R. D., Coker, L. H., Stefanick, M. L., Ockene, J., Rapp, S. R. 2005; 161 (3): 228-238

  Abstract

  Some, but not all, observational studies have suggested that moderate levels of alcohol intake may be associated with improved cognitive function and reduced risk of cognitive decline and dementia. The authors of this 1996-2002 study used data from the Women's Health Initiative Memory Study of postmenopausal combination hormone therapy to assess cross-sectional and prospective associations of self-reported alcohol intake with cognitive function. Across 39 US academic medical centers, 4,461 community-dwelling women aged 65-79 years were followed an average of 4.2 years with annual Modified Mini-Mental State Examinations and standardized protocols for detecting mild cognitive impairment and probable dementia. Compared with no intake, intake of > or =1 drink per day was associated with higher baseline Modified Mini-Mental State Examination scores (p < 0.001) and a covariate-adjusted odds ratio of 0.40 (95% confidence interval: 0.28, 0.99) for significant declines in cognitive function. Associations with incident probable dementia and mild cognitive impairment were of similar magnitude but were not statistically significant after covariate adjustment. Associations with intakes of <1 drink per day were intermediate. Moderate levels of alcohol intake may be associated with better cognition and reduced risk of significant cognitive decline; however, confounding associations with unmeasured factors cannot be ruled out.

  View details for DOI 10.1093/aje/kwi043

  View details for Web of Science ID 000226604900004

  View details for PubMedID 15671255

• The rise and fall of menopausal hormone therapy ANNUAL REVIEW OF PUBLIC HEALTH Barrett-Connor, E., Grady, D., Stefanick, M. L. 2005; 26: 115-140

  Abstract

  Clinical trials show that hormone therapy (HT) is an effective treatment for vasomotor symptoms and vaginal dryness. HT improves other symptoms including sleep and quality of life in women who have menopause symptoms. In the Women's Health Initiative controlled clinical trials, both estrogen therapy (ET) and estrogen plus progestin therapy (EPT) reduced fracture risk, neither reduced the risk of heart disease, and both increased the risk of stroke, deep vein thrombosis, and dementia. EPT, but not ET, increased breast cancer risk and reduced colon cancer risk. Differences between EPT and ET may reflect chance, baseline differences between the EPT and ET cohorts, or a progestin effect. Studies of younger women and lower HT doses with intermediate endpoints are beginning.

  View details for DOI 10.1146/annurev.publhealth.26.021304.144637

  View details for Web of Science ID 000228981500006

  View details for PubMedID 15760283

• Insulin, physical activity, and caloric intake in postmenopausal women: Breast cancer implications JOURNAL OF CLINICAL ONCOLOGY Chlebowski, R. T., Pettinger, M., Stefanick, M. L., Howard, B. V., Mossavar-Rahmani, Y., McTiernan, A. 2004; 22 (22): 4507-4513

  Abstract

  Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels.An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors.Lower BMI (P < .0001), higher levels of physical activity (P < .0001), and lower caloric intake (P < .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 microU/mL +/- 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 microU/mL +/- 16.32 SD in the lowest physical activity and highest caloric intake quintile (P < .0001).These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.

  View details for DOI 10.1200/JCO.2004.04.119

  View details for Web of Science ID 000225175600012

  View details for PubMedID 15542801

• On the importance of using multiple methods of dietary assessment EPIDEMIOLOGY Natarajan, L., Rock, C. L., Major, J. M., Thomson, C. A., Caan, B. J., Flatt, S. W., Chilton, J. A., Hollenbach, K. A., Newman, V. A., Faerber, S., Ritenbaugh, C. K., Gold, E., Stefanick, M. L., Jones, L. A., Marshall, J. R., Pierce, J. P. 2004; 15 (6): 738-745

  Abstract

  Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial.Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method.In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error.These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.

  View details for DOI 10.1097/01.ede.0000135178.36362.ef

  View details for Web of Science ID 000224697200013

  View details for PubMedID 15475724

• Sex steroid hormones in older men: Cross-sectional and longitudinal associations with bone mineral density (BMD). The osteoporotic fracture in men study (MrOS). 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research Cauley, J., Taylor, B., Fink, H., Ensrud, K., Bauer, D., Barrett-Connor, E., Marshall, L., Nevitt, M., Stefanick, M., Orwoll, E. WILEY-BLACKWELL. 2004: S16–S16

  View details for Web of Science ID 000224326800059

• Association between reported alcohol intake and changes in cognition: The Women's Health Initiative Memory Study (WHIMS) Coker, L., Rapp, S., Stefanick, M., Masaki, K., Ockene, J., Espeland, M., Langer, R., Gu, L., Shumaker, S. OXFORD UNIV PRESS INC. 2004: 82–83

  View details for Web of Science ID 000225458800241

• Postmenopausal hormone therapy and body composition - Results from the Women's Health Initiative E+P trial. 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research Chen, Z., Bassford, T., Green, S. B., LeBoff, M., Margolis, K. L., Lacroix, A., Jackson, R. D., Cauley, J., Stefanick, M. L. WILEY-BLACKWELL. 2004: S40–S40

  View details for Web of Science ID 000224326800155

• Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women - Women's Health Initiative Memory Study JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Shumaker, S. A., Legault, C., Kuller, L., Rapp, S. R., Thal, L., Lane, D. S., Fillit, H., Stefanick, M. L., Hendrix, S. L., Lewis, C. E., Masaki, K., Coker, L. H. 2004; 291 (24): 2947-2958

  Abstract

  The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.Probable dementia and MCI.In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.

  View details for Web of Science ID 000222184600024

  View details for PubMedID 15213206

• Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer 11th Annual Research Conference on Diet, Nutrition and Cancer Rock, C. L., Flatt, S. W., Thomson, C. A., Stefanick, M. L., Newman, V. A., Jones, L. A., Natarajan, L., Ritenbaugh, C., Hollenbach, K. A., Pierce, J. P., Chang, R. J. AMER SOC CLINICAL ONCOLOGY. 2004: 2379–87

  Abstract

  Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. Participants andSerum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured.The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations.Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

  View details for DOI 10.1200/JCO.2004.09.025

  View details for Web of Science ID 000222153400016

  View details for PubMedID 15197199

• Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy - The women's health initiative randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Anderson, G. L., Limacher, M., Assaf, A. R., Bassford, T., Beresford, S. A., BLACK, H., Bonds, D., Brunner, R., Brzyski, R., Caan, B., Chlebowski, R., Curb, D., Gass, M., Hays, J., Heiss, G., Hendrix, S., Howard, B. V., Hsia, J., Hubbell, A., Jackson, R., Johnson, K. C., Judd, H., Kotchen, J. M., Kuller, L., LaCroix, A. Z., Lane, D., Langer, R. D., Lasser, N., Lewis, C. E., Manson, J., Margolis, K., Ockene, J., O'Sullivan, M. J., Phillips, L., Prentice, R. L., Ritenbaugh, C., Robbins, J., Rossouw, J. E., Sarto, G., Stefanick, M. L., Van Horn, L., Wactawski-Wende, J., Wallace, R., Wassertheil-Smoller, S. 2004; 291 (14): 1701-1712

  Abstract

  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

  View details for Web of Science ID 000220788700027

  View details for PubMedID 15082697

• Estrogen plus progestin and colorectal cancer in postmenopausal women NEW ENGLAND JOURNAL OF MEDICINE Chlebowski, R. T., Wactawski-Wende, J., Ritenbaugh, C., Hubbell, F. A., Ascensao, J., Rodabough, R. J., Rosenberg, C. A., Taylor, V. M., Harris, R., Chen, C., Adams-Campbell, L. L., White, E., Alving, B., Rossouw, J., Pottern, L., Ludlam, S., McGowan, J., Prentice, R., Anderson, G., Lacroix, A., Patterson, R., McTiernan, A., Cochrane, B., Hunt, J., Tinker, L., Kooperberg, C., McIntosh, M., Wang, C. Y., Chen, C., Bowen, D., Kristal, A., Stanford, J., Urban, N., Weiss, N., White, E., Shumaker, S., Rautaharju, P., Prineas, R., Naughton, M., Stein, E., Laskarzewski, P., Cummings, S., Nevitt, M., Dockrell, M., Harnack, L., Cammarata, F., Lindenfelser, S., Psaty, B., Heckbert, S., Wassertheil-Smoller, S., Frishman, W., Wylie-Rosett, J., Barad, D., Freeman, R., Hays, J., Young, R., Anderson, J., Lithgow, S., Bray, P., Manson, J., Buring, J., Gaziano, J. M., Rexrode, K., Chae, C., Assaf, A. R., WHEELER, C., Eaton, C., Cyr, M., Phillips, L., PEDERSEN, M., Strickland, O., Huber, M., Porter, V., Beresford, S. A., Taylor, V. M., Woods, N. F., Henderson, M., Kestin, M., Hsia, J., Gaba, N., Ascensao, J., Chlebowski, R., Detrano, R., Nelson, A., Heiner, J., Marshall, J., Ritenbaugh, C., Valanis, B., Elmer, P., Stevens, V., Karanja, N., Caan, B., Sidney, S., Bailey, G., HIRATA, J., Kotchen, J. M., Barnabei, V., Kotchen, T. A., Gilligan, M. A., Neuner, J., Howard, B. V., Adams-Campbell, L., Passaro, M., Rainford, M., Agurs-Collins, T., Van Horn, L., Greenland, P., Khandekar, J., Liu, K., Rosenberg, C., BLACK, H., Powell, L., Mason, E., Stefanick, M. L., Hlatky, M. A., Chen, B., Stafford, R. S., Giudice, L. C., Lane, D., Granek, I., Lawson, W., San Roman, G., Messina, C., Jackson, R., Harris, R., Paskett, E., Mysiw, W. J., Blumenfeld, M., Lewis, C. E., Oberman, A., Shikany, J. M., Safford, M., Britt, B. K., Bassford, T., Mattox, J., Ko, M., Lohman, T., Wactawski-Wende, J., Trevisan, M., Smit, E., Graham, S., Chang, J., Robbins, J., Yasmeen, S., Lindfors, K., Stern, J., Hubbell, A., Frank, G., Wong, N., Greep, N., Monk, B., Judd, H., Heber, D., Elashoff, R., Langer, R. D., Criqui, M. H., Talavera, G. T., Garland, C. F., Hanson, R. E., Gass, M., Wernke, S., Watts, N., Limacher, M., Perri, M., Kaunitz, A., Williams, R. S., Brinson, Y., Curb, D., Petrovitch, H., Rodriguez, B., Masaki, K., Sharma, S., Wallace, R., Torner, J., JOHNSON, S., Snetselaar, L., VanVoorhis, B., Ockene, J., Rosal, M., Ockene, I., Yood, R., Aronson, P., Lasser, N., Singh, B., Lasser, V., Kostis, J., O'Sullivan, M. J., PARKER, L., Estape, R., Fernandez, D., Margolis, K. L., Grimm, R. H., Hunninghake, D. B., LaValleur, J., Kempainen, S., Brunner, R., Graettinger, W., Oujevolk, V., Heiss, G., Haines, P., Ontjes, D., Sueta, C., Wells, E., Kuller, L., Cauley, J., Milas, N. C., Johnson, K. C., Satterfield, S., Ke, R. W., Vile, J., Tylavsky, F., Brzyski, R., Schenken, R., Trabal, J., Rodriguez-Sifuentes, M., Mouton, C., Sarto, G., Laube, D., McBride, P., Mares-Perlman, J., Loevinger, B., Bonds, D., BURKE, G., Crouse, R., Parsons, L., Vitolins, M., Hendrix, S., Simon, M., McNeely, G., Gordon, P., MAKELA, P., Allen, C., Dougherty, S., Carleton, R. 2004; 350 (10): 991-1004

  Abstract

  Although the Women's Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants.In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication.There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006).Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.

  View details for Web of Science ID 000189363600007

  View details for PubMedID 14999111

• Women's Ischemic Syndrome Evaluation - Current status and future research directions - Report of the National Heart, Lung and Blood Institute Workshop - October 2-4, 2002 - Section 4 - Lessons from hormone replacement trials NHLBI Workshop on Women and Ischemia Syndrome Evaluation (WISE) Waters, D. D., GORDON, D., Rossouw, J. E., Cannon, R. O., Collins, P., Herrington, D. M., Hsia, J., Langer, R., Mosca, L., Ouyang, P., Sopko, G., Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2004: E53–E55

  View details for DOI 10.1161/01.CIR.0000116209.25597.AE

  View details for Web of Science ID 000189005500026

  View details for PubMedID 14970126

• Telephone counseling intervention increases intakes of micronutrient- and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors JOURNAL OF NUTRITION Pierce, J. P., Newman, V. A., Flatt, S. W., Faerber, S., Rock, C. L., Natarajan, L., Caan, B. J., Gold, E. B., Hollenbach, K. A., Wasserman, L., Jones, L., Ritenbaugh, C., Stefanick, M. L., Thomson, C. A., Kealey, S. 2004; 134 (2): 452-458

  Abstract

  Although a large body of evidence suggests that diet may play an important role in cancer prevention, randomized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk. The Women's Healthy Eating and Living (WHEL) Study, a randomized controlled trial of the role diet modification may play in future breast cancer events, introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber, low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals. This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants, assessed through 24-h recalls and validated with plasma carotenoid concentrations. At 12 mo, the intervention group reported a significantly increased daily vegetable intake (+vegetable juice) of 7.1 servings (+82%) and fruit intake of 3.9 servings (+18%). Fiber intake increased from 3.04 to 4.16 g/(MJ. d), whereas energy from fat decreased significantly from 28.6 to 23.7%. Plasma carotenoid concentrations increased significantly, i.e., alpha-carotene (+223%); beta-carotene (+87%); lutein (+29%); and lycopene (+17%). In the comparison group, dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo. The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables, fruit and fiber intakes, enabling an investigation of the potential cancer preventive effects of these food components.

  View details for Web of Science ID 000188708100026

  View details for PubMedID 14747688

• Plasma triacylglycerol and HDL cholesterol concentrations confirm self-reported changes in carbohydrate and fat intakes in women in a diet intervention trial JOURNAL OF NUTRITION Rock, C. L., Flatt, S. W., Thomson, C. A., Stefanick, M. L., Newman, V. A., Jones, L., Natarajan, L., Pierce, J. P., Chang, R. J., WITZTUM, J. L. 2004; 134 (2): 342-347

  Abstract

  Diet intervention trials are currently testing whether reduced fat intake can reduce the risk and progression of breast cancer. Energy from dietary fat is generally replaced by energy from carbohydrate in these studies, and altering the proportion of energy from dietary carbohydrate and fat has been shown to affect plasma lipid concentrations in controlled feeding studies. The purpose of this study was to examine the effect of increased carbohydrate and reduced fat intakes on plasma lipids in a randomized, controlled trial that is testing the effect of diet modification on risk for recurrence and survival in women previously treated for breast cancer. Plasma concentrations of lipids and related factors were measured at enrollment and 1-y follow-up in 393 women enrolled in the trial. Dietary goals for the intervention group focused on an increase in vegetable, fruit and fiber intakes, and reduced fat intake. Women assigned to the intervention group significantly reduced fat intake (from 28.1 to 21.0% of energy), and significantly increased intakes of carbohydrate (from 56.9 to 65.3% of energy) and fiber (from 21.0 to 29.6 g/d) (P < 0.05). Body weight did not change significantly in either study group. A small but significant increase in fasting plasma triacylglycerol concentration, and decreases in HDL cholesterol and apoprotein-A1 concentrations, were observed in the intervention group (P < 0.05) but not in the comparison group. Changes in total cholesterol, LDL cholesterol, apoprotein-B, lipoprotein (a), and insulin concentrations, and in the LDL cholesterol/HDL cholesterol ratio, were not observed in either group. The lipid responses that were observed in this study provide biological evidence that validates the self-reported change in dietary intakes of fat and carbohydrate in response to the intervention efforts. The degree of change in these lipid concentrations was small and does not suggest increased cardiovascular disease risk.

  View details for Web of Science ID 000188708100008

  View details for PubMedID 14747670

• National use of postmenopausal hormone therapy - Annual trends and response to recent evidence JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hersh, A. L., Stefanick, M. L., Stafford, R. S. 2004; 291 (1): 47-53

  Abstract

  Postmenopausal hormone therapy use increased dramatically during the past 2 decades because of a prevailing belief in its health benefits. Recent evidence from randomized trials published in July 2002 demonstrated adverse cardiovascular disease events and other risks with hormone therapy in the form of oral estrogen combined with progestin.To describe patterns of hormone therapy use from 1995 until July 2003, including the impact of recent evidence.Two databases were used to describe national trends in hormone therapy use from January 1995 to July 2003. The National Prescription Audit database provided data on the number of hormone therapy prescriptions filled by retail pharmacies and the National Disease and Therapeutic Index database provided data on patient visits to office-based physicians during which hormone therapy was prescribed.Annual number of hormone therapy prescriptions and characteristics of visits to physicians during which hormone therapy was prescribed.Annual hormone therapy prescriptions increased from 58 million in 1995 to 90 million in 1999, representing approximately 15 million women per year, then remained stable through June 2002. Adoption of new oral estrogen/progestin combinations, primarily Prempro, accounted for most of this growth. Obstetrician/gynecologists provided more than 70% of hormone therapy prescriptions, and more than one third of patients were older than 60 years. Following the publication of trial results in July 2002, hormone therapy prescriptions declined in successive months. Relative to January-June 2002, prescriptions from January-June 2003 declined by 66% for Prempro and 33% for Premarin. Small increases were observed in vaginal formulations and in new prescriptions for low-dose Premarin. If prescription rates observed through July 2003 remain stable, a decline to 57 million prescriptions for 2003, similar to the rate in 1995, is projected.Clinical practice responded rapidly to recent evidence of harms associated with hormone therapy. Since July 2002, many patients have discontinued hormone therapy or are tapering to lower doses.

  View details for Web of Science ID 000187836000018

  View details for PubMedID 14709575

• The Women's Health Initiative postmenopausal hormone trials: Overview and baseline characteristics of participants ANNALS OF EPIDEMIOLOGY Stefanick, M. L., Cochrane, B. B., Hsia, J., Barad, D. H., Liu, J. H., Johnson, S. R. 2003; 13 (9): S78-S86

  View details for DOI 10.1016/S1047-2797(03)00045-0

  View details for Web of Science ID 000186363200004

  View details for PubMedID 14575940

• Effects of estrogen plus progestin on risk of fracture and bone mineral density - The Women's Health Initiative randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Cauley, J. A., Robbins, J., Chen, Z., Cummings, S. R., Jackson, R. D., LaCroix, A. Z., LeBoff, M., Lewis, C. E., McGowan, J., Neuner, J., Pettinger, M., Stefanick, M. L., Wactawski-Wende, J., Watts, N. B. 2003; 290 (13): 1729-1738

  Abstract

  In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures.To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures.Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years.Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk.Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54).This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

  View details for Web of Science ID 000185606100022

  View details for PubMedID 14519707

• Estrogen plus progestin and the risk of coronary heart disease NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Hsia, J., Johnson, K. C., Rossouw, J. E., Assaf, A. R., Lasser, N. L., Trevisan, M., Black, H. R., Heckbert, S. R., Detrano, R., Strickland, O. L., Wong, N. D., Crouse, J. R., Stein, E., Cushman, M., Alving, B., Rossouw, J. E., Pottern, L., Ludlam, S., McGowan, J. A., Prentice, R., Anderson, G., Lacroix, A., Patterson, R., McTiernan, A., Cochrane, B., Hunt, J., Tinker, L., Kooperberg, C., McIntosh, M., Wang, C. Y., Chen, C., Bowen, D., Kristal, A., Stanford, J., Urban, N., Weiss, N., White, E., Shumaker, S., Rautaharju, P., Prineas, R., Naughton, M., Stein, E., Laskarzewski, P., Cummings, S., Nevitt, M., Dockrell, M., Harnack, L., Cammarata, F., Lindenfelser, S., Psaty, B., Heckbert, S., Wassertheil-Smoller, S., Frishman, W., Wylie-Rosett, J., Barad, D., Freeman, R., Hays, J., Young, R., Anderson, J., Lithgow, S., Bray, P., Manson, J., Buring, J., Gaziano, J. M., Rexrode, K., Chae, C., Assaf, A. R., Carleton, R., WHEELER, C., Eaton, C., Cyr, M., Phillips, L., PEDERSEN, M., Strickland, O., Huber, M., Porter, V., Beresford, S. A., Taylor, V. M., Woods, N. F., Henderson, M., Kestin, M., Hsia, J., Gaba, N., Ascensao, J., Laowattana, S., Chlebowski, R., Detrano, R., Nelson, A., Heiner, J., Marshall, J., Ritenbaugh, C., Valanis, B., Elmer, P., Stevens, V., Karanja, N., Caan, B., Sidney, S., Bailey, G., HIRATA, J., Kotchen, J. M., Barnabei, V., Kotchen, T. A., Gilligan, M. A., Neuner, J., Howard, B. V., Adams-Campbell, L., Passaro, M., Rainford, M., Agurs-Collins, T., Van Horn, L., Greenland, P., Khandekar, J., Liu, K., Rosenberg, C., BLACK, H., Powell, L., Mason, E., Stefanick, M. L., Hlatky, M. A., Chen, B., Stafford, R. S., Giudice, L. C., Lane, D., Granek, I., Lawson, W., San Roman, G., Messina, C., Jackson, R., Harris, R., Frid, D., Mysiw, W. J., Blumenfeld, M., Lewis, C. E., Oberman, A., Fouad, M. N., Shikany, J. M., West, D. S., Bassford, T., Mattox, J., Ko, M., Lohman, T., Trevisan, M., Wactawski-Wende, J., Graham, S., Chang, J., Smit, E., Robbins, J., Yasmeen, S., Lindfors, K., Stern, J., Hubbell, A., Frank, G., Wong, N., Greep, N., MoOnk, B., Judd, H., Heber, D., Elashoff, R., Langer, R. D., Criqui, M. H., Talavera, G. T., Garland, C. F., Hanson, R. E., Gass, M., Wernke, S., Watts, N., Limacher, M., Perri, M., Kaunitz, A., Williams, R. S., Brinson, Y., Curb, D., Petrovitch, H., Rodriguez, B., Masaki, K., Sharma, S., Wallace, R., Torner, J., JOHNSON, S., Snetselaar, L., VanVoorhis, B., Ockene, I., Yood, R., Aronson, P., Lasser, N., Hymowitz, N., Lasser, V., Safford, M., Kostis, J., O'Sullivan, M. J., PARKER, L., Estape, R., Fernandez, D., Margolis, K. L., Grimm, R. H., Hunninghake, D. B., LaValleur, J., Hall, K. M., Brunner, R., St Jeor, S., Graettinger, W., Oujevolk, V., Heiss, G., Haines, P., Ontjes, D., Sueta, C., Wells, E., Kuller, L., Caggiula, A., Cauley, J., Berga, S., Milas, N. C., Johnson, K. C., Satterfield, S., Ke, T. W., Vile, J., Tylavsky, F., Brzyski, R., Schenken, R., Trabal, J., Rodriguez-Sifuentes, M., Mouton, C., Allen, C., Laube, D., McBride, P., Mares-Perlman, J., Loevinger, B., BURKE, G., Crouse, R., Parsons, L., Vitolins, M., Hendrix, S., Simon, M., McNeeley, G., Gordon, P., MAKELA, P. 2003; 349 (6): 523-534

  Abstract

  Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI).The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD).After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD.Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.

  View details for Web of Science ID 000184563500003

  View details for PubMedID 12904517

• Influence of estrogen plus progestin on breast, cancer and mammography in healthy postmenopausal women - The Women's Health Initiative Randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Chlebowski, R. T., Hendrix, S. L., Langer, R. D., Stefanick, M. L., Gass, M., Lane, D., Rodabough, R. J., Gilligan, M. A., Cyr, M. G., Thomson, C. A., Khandekar, J., Petrovitch, H., McTiernan, A. 2003; 289 (24): 3243-3253

  Abstract

  The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

  View details for Web of Science ID 000183704600017

  View details for PubMedID 12824205

• Effect of estrogen plus progestin on global cognitive function in postmenopausal women - The Women's Health Initiative Memory Study: A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rapp, S. R., Espeland, M. A., Shumaker, S. A., Henderson, V. W., Brunner, R. L., Manson, J. E., Gass, M. L., Stefanick, M. L., Lane, D. S., Hays, J., Johnson, K. C., Coker, L. H., Dailey, M., Bowen, D. 2003; 289 (20): 2663-2672

  Abstract

  Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women.A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002.Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236).Global cognitive function measured annually with the Modified Mini-Mental State Examination.The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P =.03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (> or =2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P =.008).Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.

  View details for Web of Science ID 000183075600025

  View details for PubMedID 12771113

• A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study CONTROLLED CLINICAL TRIALS Pierce, J. P., Faerber, S., Wright, F. A., Rock, C. L., Newman, V., Flatt, S. W., Kealey, S., Jones, V. E., Caan, B. J., Gold, E. B., Haan, M., Hollenbach, K. A., Jones, L., Marshall, J. R., Ritenbaugh, C., Stefanick, M. L., Thomson, C., Wasserman, L., Natarajan, L., Thomas, R. G., Gilpin, E. A. 2002; 23 (6): 728-756

  Abstract

  The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

  View details for Web of Science ID 000179835100010

  View details for PubMedID 12505249

• Menopausal symptoms in older women and the effects of treatment with hormone therapy OBSTETRICS AND GYNECOLOGY Barnabei, V. M., Grady, D., Stovall, D. W., Cauley, J. A., Lin, F., Stuenkel, C. A., Stefanick, M. L., Pickar, J. H. 2002; 100 (6): 1209-1218

  Abstract

  In some women, hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses. The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented.We used data from the Heart and Estrogen/Progestin Replacement Study, a blinded, clinical trial among 2763 women with documented coronary disease and a uterus who were randomized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo. Participants were queried at baseline and annually regarding menopausal symptoms. Breast symptoms were self-reported, and uterine bleeding was recorded on a daily diary.Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants, whose average age was 67 years and who averaged 18 years since menopause. At baseline, 16% of women reported frequent hot flashes, 26% vaginal dryness, 10% genital irritation, 55% trouble sleeping, and 53% early awakening. Women assigned to hormone therapy reported less frequent hot flashes, vaginal dryness, and trouble sleeping compared with women assigned to placebo, but more frequent vaginal discharge, genital irritation, uterine bleeding, and breast symptoms. The reporting of breast symptoms among women in the hormone group decreased from 40% at 1 year to 13% by the 4th year. Uterine bleeding was reported by 31% and spotting by an additional 33% of women in the hormone group during the 1st year of treatment; by the 4th year, these proportions had fallen to 11% and 20%, respectively.Symptoms typically attributed to menopause are common in elderly women. Postmenopausal hormone therapy reduces hot flashes, trouble sleeping, and vaginal dryness, but at standard doses in elderly women is associated with vaginal discharge, genital irritation, uterine bleeding, and breast symptoms.

  View details for Web of Science ID 000179526600011

  View details for PubMedID 12468165

• Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States) CANCER CAUSES & CONTROL Morimoto, L. M., White, E., Chen, Z., Chlebowski, R. T., Hays, J., Kuller, L., Lopez, A. M., Manson, J., Margolis, K. L., Muti, P. C., Stefanick, M. L., McTiernan, A. 2002; 13 (8): 741-751

  Abstract

  Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50-79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993-1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) >31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62-3.93), compared to slimmer women (baseline BMI < 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88-2.01).Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.

  View details for Web of Science ID 000178063700007

  View details for PubMedID 12420953

• Compliance with national cholesterol education program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia: The women's health initiative AMERICAN JOURNAL OF MEDICINE Hsia, J., Rodabough, R., Rosal, M. C., Cochrane, B., Howard, B. V., Snetselaar, L., FRISHMAN, W. H., Stefanick, M. L. 2002; 113 (5): 384-392

  Abstract

  Dietary therapy remains the first line of treatment for patients with high blood cholesterol levels. Among free-living persons, compliance with National Cholesterol Education Program (NCEP) dietary recommendations is uncertain.We performed a cross-sectional, baseline analysis of 91,627 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Among women with self-reported hypercholesterolemia, we ascertained factors associated with compliance with National Cholesterol Education Program dietary recommendations, defined for the Step II diet as

  View details for Web of Science ID 000178799400005

  View details for PubMedID 12401533

• Walking compared with vigorous exercise for the prevention of cardiovascular events in women NEW ENGLAND JOURNAL OF MEDICINE Manson, J. E., Greenland, P., LaCroix, A. Z., Stefanick, M. L., Mouton, C. P., Oberman, A., Perri, M. G., Sheps, D. S., Pettinger, M. B., Siscovick, D. S. 2002; 347 (10): 716-725

  Abstract

  The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse.We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events.An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk.These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.

  View details for Web of Science ID 000177765800003

  View details for PubMedID 12213942

• Stage of motivational readiness: Predictive ability for exercise behavior AMERICAN JOURNAL OF HEALTH BEHAVIOR Young, D. R., King, A. C., Sheehan, M., Stefanick, M. L. 2002; 26 (5): 331-341

  Abstract

  To determine if stage of motivational readiness for exercise predicted adherence to a 9-month exercise intervention.Three hundred forty-two individuals were randomized into a diet and physical activity trial. The exercise goal was to complete or add at least 10 miles of weekly brisk walking or jogging. Adherence was determined from logs.Sixty-four percent of men and 34% of women reported an increase of at least 10 miles per week. Adherence did not differ by baseline exercise motivational readiness stage.Future work should determine in what contexts stage-targeted interventions are most successful for adoption and maintenance of physical activity.

  View details for Web of Science ID 000177281200002

  View details for PubMedID 12206443

• Risks and benefits of estrogen plus progestin in healthy postmenopausal women - Principal results from the Women's Health Initiative randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Rossouw, J. E., Anderson, G. L., Prentice, R. L., LaCroix, A. Z., Kooperberg, C., Stefanick, M. L., Jackson, R. D., Beresford, S. A., Howard, B. V., Johnson, K. C., Kotchen, M., Ockene, J. 2002; 288 (3): 321-333

  Abstract

  Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

  View details for Web of Science ID 000176807000024

  View details for PubMedID 12117397

• Effects of food availability on serum insulin and lipid concentrations in free-ranging baboons AMERICAN JOURNAL OF PRIMATOLOGY Kemnitz, J. W., Sapolsky, R. M., Altmann, J., Muruthi, P., Mott, G. E., Stefanick, M. L. 2002; 57 (1): 13-19

  Abstract

  The relationship between food availability and metabolic physiology was studied in groups of free-ranging baboons (Papio spp.) living in the Amboseli National Park and the Masai Mara National Reserve of Kenya. Three groups subsisted entirely on natural forage, while two other groups lived near tourist facilities and often consumed food wastes from these lodges. The refuse provided a very accessible food source with relatively high caloric density. Consumption of the refuse was associated with reduced locomotion. Sexually mature individuals from all five groups were sedated surreptitiously in the early morning and blood samples were collected. Compared to animals foraging exclusively in the wild, animals that supplemented their diet with the refuse items had two- to threefold elevations in serum insulin concentrations, as well as increased total cholesterol (C), HDL-C, and VLDL+LDL-C levels. No sex differences in physiological measures were observed except in body mass. Elevated serum insulin, and cholesterol and lipoprotein concentrations influence the development of cardiovascular disease and have been shown to be subject to dietary manipulation and exercise under controlled conditions. The present results suggest potentially deleterious effects of a highly accessible, calorically dense food source, and associated reduction of physical activity for baboons living in an otherwise natural environment.

  View details for DOI 10.1002/ajp.1083

  View details for Web of Science ID 000175326700002

  View details for PubMedID 11977122

• Men gain additional psychological benefits by adding exercise to a weight-loss program OBESITY RESEARCH Kiernan, M., King, A. C., Stefanick, M. L., Killen, J. D. 2001; 9 (12): 770-777

  Abstract

  Adding exercise to a comprehensive weight-loss program might not only attenuate any psychological distress associated with weight-loss attempts but also may provide psychological benefits. This study examined whether a diet-plus-exercise weight-loss program improved psychological outcomes more than a diet-only weight-loss program or an assessment-only control group.This study was part of a larger 1-year randomized weight-loss trial examining the effects of diet and exercise on cardiovascular disease risk factors in 264 overweight adults. Psychological measures specific to weight control (e.g., cognitive restraint, disinhibition, hunger, and body dissatisfaction) as well as traditional measures of psychological distress (e.g., symptoms of depression, anxiety, and stress) were obtained at baseline and 1 year.Men and women in either weight-loss program reported greater restraint, less disinhibition, and less hunger at 1 year than those in no program. Men in the diet-plus-exercise program experienced additional increases in restraint and decreases in hunger than did men in the diet-only program. Women in the diet-plus-exercise program did not experience additional psychological benefits specific to weight control than those in the diet-only program, despite increases in aerobic capacity.The pattern seen for overweight men in the diet-plus-exercise program at 1 year-greater restraint, less disinhibition, and less hunger-is similar to the pattern seen in successful weight maintainers. These results underscore the need for innovative strategies that will enhance and sustain the pattern of psychological benefits specific to weight control associated with successful weight loss, especially for overweight women.

  View details for Web of Science ID 000172892000006

  View details for PubMedID 11743061

• Reduction in fat intake is not associated with weight loss in most women alter breast cancer diagnosis - Evidence from a randomized controlled trial CANCER Rock, C. L., Thomson, C., Caan, B. J., Flatt, S. W., Newman, V., Ritenbaugh, C., Marshall, J. R., Hollenbach, K. A., Stefanick, M. L., Pierce, J. P. 2001; 91 (1): 25-34

  Abstract

  A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence.Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index.The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index.For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.

  View details for Web of Science ID 000168675200004

  View details for PubMedID 11148556

• Correlates of high HDL cholesterol among women with coronary heart disease AMERICAN HEART JOURNAL Bittner, V., Simon, J. A., Fong, J., Blumenthal, R. S., Newby, K., Stefanick, M. L. 2000; 139 (2): 288-296

  Abstract

  The National Cholesterol Education Program (NCEP) has designated high-density lipoprotein cholesterol (HDL-C) > or =60 mg/dL a "negative" coronary heart disease (CHD) risk factor, but a substantial proportion of coronary events occur among women despite high HDL-C levels.The objective of this study was to characterize postmenopausal women with prevalent CHD despite HDL-C > or =60 mg/dL and to identify factors that may attenuate the protective effect of high HDL-C. We analyzed baseline data from a randomized, double-blind study of estrogen/progestin replacement therapy in 2763 postmenopausal women <80 years old with CHD. Demographics, CHD risk factors, medications, anthropometrics, and lipid levels were compared among women with low, normal, and high HDL-C by NCEP criteria with and without stratification by use of lipid-lowering medications. Independent correlates of high HDL-C were determined by logistic regression analysis. HDL-C > or =60 mg/dL was present in 20% of participants. Women with high HDL-C were older, better educated, had fewer CHD risk factors, lower triglyceride levels and total cholesterol/HDL-C ratio, and were more likely to report past estrogen and current calcium antagonist, niacin, and statin use. beta-Blocker, diuretic, and fibrate use was less common. Older age, alcohol consumption, niacin, and calcium antagonist use and prior estrogen use were independently associated with high HDL-C, whereas waist-to-hip ratio, smoking, triglyceride level, and beta-blocker and fibrate use were inversely associated (all P <.05).High HDL-C, as defined by the NCEP, occurred in 20% of women with CHD in this cohort without a concomitantly higher prevalence of other CHD risk factors. Redefinition of "high" HDL-C levels for women may be warranted.

  View details for Web of Science ID 000085253300014

  View details for PubMedID 10650302

• Effect of hormone replacement therapy on the validity of the Friedewald equation in postmenopausal women: The Postmenopausal Estrogen/Progestins Interventions (PEPI) trial JOURNAL OF CLINICAL EPIDEMIOLOGY Legault, C., Stefanick, M. L., Miller, V. T., Marcovina, S. M., Schrott, H. G. 1999; 52 (12): 1187-1195

  Abstract

  The Friedewald equation is often used to estimate low-density lipoprotein cholesterol (LDL-C). Hormone therapy is known to raise triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and alter lipid contents of lipoproteins. We compared Friedewald estimated LDL-C to measured LDL-C in PEPI participants on placebo or four different hormone treatment groups. At baseline, the 0.2 coefficient for triglyceride (TG) was accurate for all five treatment groups. Among women who took >80% of their pills and whose TG was <4.5 mmol/l (400 mg/dl), LDL-C was underestimated for 69-82% of the participants in the active treatment groups, compared to 50% in the placebo group. After 3 years of therapy, the TG coefficient that offered a better fit of the Friedewald equation in the active treatment groups was 0.39 for the equation in mmol/l (0.17 for the equation in mg/dl). Using this coefficient is clearly warranted for greater accuracy in research studies.

  View details for Web of Science ID 000083817000008

  View details for PubMedID 10580781

• Physical activity for preventing and treating obesity-related dyslipoproteinemias Conference on Physical Activity in the Prevention and Treatment of Obesity and its Comorbidities Stefanick, M. L. LIPPINCOTT WILLIAMS & WILKINS. 1999: S609–S618

  Abstract

  The clinical trial data were reviewed on effects of physical activity on obesity-related dyslipoproteinemias (specifically low HDL-cholesterol (HDL-C), elevated triglycerides (TG), and high total and LDL-cholesterol (TC and LDL-C)) in adult men and women.Effort was made to identify all randomized clinical trials (RCT), with exercise intervention programs of at least 4 months' duration, which had lipoprotein outcomes. Those that had both an exercise only intervention and control groups or both a diet plus exercise and identical diet only intervention groups were reviewed. Tables were developed of baseline characteristics and weight and lipoprotein changes for aerobic exercise trials by body mass index: 1) < 25.0 kg x m(-2), 2) 25.0-29.9 kg x m(2), and 3) > or = 30.0 kg x m(-2)and for studies involving resistance exercise or increased energy expenditure from daily activities versus structured exercise programs.Very few RCT were found that specifically addressed the role of physical activity in preventing or treating obesity-related adverse lipoprotein levels. There was essentially no evidence found in lean or overweight men or women to support a specific role for exercise in improving undesirable lipoprotein levels; however, trial data strongly suggest that the addition of exercise to a hypocaloric, reduced-fat diet improves HDL-C and TG in men and women with generally desirable initial levels and reduces LDL-C in men and women with initially elevated LDL-C levels. The evidence is also reasonably strong that weight loss, including that achieved solely by exercise, improves HDL-C and TG in obese men, without reducing LDL-C, whereas it remains weak for women. There are also virtually no trial data to support a role for resistance exercise or an increase in daily living activities for improving obesity-related lipoproteins.Current evidence from RCT is too limited to determine whether physical activity can raise low HDL-C or lower high TG or LDL-C levels in overweight and obese individuals.

  View details for Web of Science ID 000083756700020

  View details for PubMedID 10593536

• Factors associated with weight gain in women after diagnosis of breast cancer JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION Rock, C. L., Flatt, S. W., Newman, V., Caan, B. J., Haan, M. N., Stefanick, M. L., Faerber, S., Pierce, J. P. 1999; 99 (10): 1212-?

  Abstract

  To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women.Descriptive cross-sectional study.1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses.Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score.Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.

  View details for Web of Science ID 000083014700017

  View details for PubMedID 10524383

• Effect of postmenopausal hormones on inflammation-sensitive proteins - The Postmenopausal Estrogen/Progestin Interventions (PEPI) Study CIRCULATION Cushman, M., Legault, C., Barrett-Connor, E., Stefanick, M. L., Kessler, C., Judd, H. L., Sakkinen, P. A., Tracy, R. P. 1999; 100 (7): 717-722

  Abstract

  Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest.Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline.Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.

  View details for Web of Science ID 000082082900007

  View details for PubMedID 10449693

• Knowledge and perceived risk of major diseases in middle-aged and older women HEALTH PSYCHOLOGY Wilcox, S., Stefanick, M. L. 1999; 18 (4): 346-353

  Abstract

  Women's (N = 200; 41-95 years) knowledge of mortality risks and their perceived general risk, personal risk, control, and preventability of coronary heart disease (CHD) and breast, colon, and lung cancer were examined. Middle-aged (MA) women were more accurate in their mortality knowledge for MA men than for MA women and were more accurate for MA than for older (OA) men and women. OA women, in contrast, were least accurate in their mortality knowledge for OA women compared with all other target groups; only 34% knew that CHD is the leading cause of death in OA women. Participants also overestimated a woman's risk of death from breast cancer and underestimated the risk from lung and colon cancer. Ratings of perceived risk, control, and preventability varied as a function of disease. OA women in particular appear to lack knowledge regarding women's risk of major diseases. Results have implications for women's health behaviors and medical decisions.

  View details for Web of Science ID 000081525500004

  View details for PubMedID 10431935

• Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol NEW ENGLAND JOURNAL OF MEDICINE Stefanick, M. L., Mackey, S., Sheehan, M., Ellsworth, N., Haskell, W. L., Wood, P. D. 1998; 339 (1): 12-20

  Abstract

  Guidelines established by the National Cholesterol Education Program (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein levels. Little is known, however, about the effects of exercise or the NCEP diet, which is moderately low in fat and cholesterol, in persons with lipoprotein levels that place them at high risk for coronary heart disease.We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or =44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus exercise, or to a control group, which received no intervention.Dietary intake of fat and cholesterol decreased during the one-year study (P<0.001), as did body weight, in women and men in either the diet group or the diet-plus-exercise group, as compared with the controls (P<0.001) and the exercise group (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups, for subjects of either sex. The serum level of LDL cholesterol was significantly reduced among women (a decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg per deciliter) in the diet-plus-exercise group, as compared with the control group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group (3.6+/-18.8 mg per deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the controls.The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.

  View details for Web of Science ID 000074500000003

  View details for PubMedID 9647874

• Characteristics of successful and unsuccessful dieters: An application of signal detection methodology ANNALS OF BEHAVIORAL MEDICINE Kiernan, M., King, A. C., Kraemer, H. C., Stefanick, M. L., Killen, J. D. 1998; 20 (1): 1-6

  Abstract

  Signal detection methods were used to identify predictors of successful weight loss in 177 mildly to moderately overweight women and men assigned to one of two weight-loss programs. Predictors included initial demographic, physiological, behavioral, and psychosocial characteristics, and program type (e.g. diet-only and diet-plus-exercise). Successful weight loss was defined as a loss of at least two units of body mass index at one year. Four subgroups were identified. Participants in the diet-plus-exercise program who were initially more satisfied with their bodies and did not have a history of repeated weight loss were most likely to succeed (63% succeeded). In contrast, participants assigned to the diet-plus-exercise program who were either extremely dissatisfied with their bodies or who had a history of repeated weight loss were at similar risk for failure as participants in the diet-only program (only 26% to 35% succeeded). The results underscore the potential utility of exploring these subgroups further to inform the development of new treatment strategies to increase the likelihood of success.

  View details for Web of Science ID 000075741800001

  View details for PubMedID 9755345

• Effect of postmenopausal hormone therapy on body weight and waist and hip girths JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Espeland, M. A., Stefanick, M. L., KRITZSILVERSTEIN, D., Fineberg, S. E., Waclawiw, M. A., James, M. K., Greendale, G. A. 1997; 82 (5): 1549-1556

  Abstract

  Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth.

  View details for Web of Science ID A1997WX55100041

  View details for PubMedID 9141548

• Physical activity and lipid metabolism Consensus Development Conference on Physical Activity and Cardiovascular Health Stefanick, M. L. HUMAN KINETICS PUBL. 1997: 98–104

  View details for Web of Science ID A1997BH67L00012

• Effects of hormone replacement therapy on endometrial histology in postmenopausal women - The Postmenopausal Estrogen Progestin Interventions (PEPI) trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Judd, H. L., Wasilauskas, C., JOHNSON, S., Merino, M., BARRETTCONNOR, E., Trabal, J., Miller, V. T., Barnabei, V., Levin, G., Bush, T., Foster, D., Zacur, H., Woodruff, J. D., Stefanick, M., AKANA, A., Heinrichs, W. L., OHANLAN, K., Buyalos, R. P., Greendale, G., Lozano, K., CarrionPetersen, L., CAVERO, C., Langer, R., Schrott, H. G., Benda, J. A., DEPROSSE, C., Fedderson, D., Johnson, S. R., Ahmad, M. M., Brown, H. P., Schenken, R. S., RODRIGUEZSIFUENTES, M., VALENTE, P. T., Espeland, M., Lane, K., Legault, C., MEBANESIMS, I. L., Kelaghan, J., McGowan, J., Fradkin, J., Sherman, S., Scully, R. 1996; 275 (5): 370-375

  View details for Web of Science ID A1996TT30300030

• DISTRIBUTION AND CORRELATES OF PLASMA-FIBRINOGEN IN MIDDLE-AGED WOMEN - INITIAL FINDINGS OF THE POSTMENOPAUSAL ESTROGEN-PROGESTIN INTERVENTIONS (PEPI) STUDY ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Stefanick, M. L., Legault, C., Tracy, R. P., Howard, G., Kessler, C. M., Lucas, D. L., Bush, T. L. 1995; 15 (12): 2085-2093

  Abstract

  Fibrinogen levels have been reported in cohort and case-control studies to be positively related to the development of coronary heart disease. This report presents the distribution and determinants of fibrinogen in women enrolling in a 3-year randomized trial of hormone replacement therapy (HRT), the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. Fasting plasma fibrinogen levels were measured in 874 postmenopausal women, aged 45 to 65 years, who had not used HRT for at least 3.5 months. Mean (+/- SD) fibrinogen level was 2.83 +/- 0.45 g/L. There was a significant positive association between fibrinogen and age (P = .03). Significantly higher (P < .005) fibrinogen levels were seen in current smokers versus nonsmokers (2.94 versus 2.81 g/L), in women who reported consuming fewer than 12 alcoholic drinks in the 12 months before the baseline visit versus higher consumption (2.90 versus 2.79 g/L), and in women who reported never versus ever having used HRT (2.90 versus 2.77 g/L). Self-reported leisure time physical activity (LTPA) was negatively associated (P = .0001) with fibrinogen levels as follows: inactive (2.84 g/L), light (2.89 g/L), moderate (2.80 g/L), and heavy (2.60 g/L), with significantly (P = .0001) lower levels in women who reported heavy LTPA versus each of the other categories and in women reporting moderate versus light LTPA. A strong positive correlation was found between fibrinogen and body mass index (BMI) (r = .32; P < .0001). In a model that included age, smoking, alcohol intake, prior HRT, LTPA, and BMI, LTPA was no longer a statistically significant predictor of fibrinogen level, while associations with other variables remained significant.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1995TJ36800001

  View details for PubMedID 7489228

• PHYSICAL AND LABORATORY MEASUREMENTS IN THE PEPI TRIAL CONTROLLED CLINICAL TRIALS Wood, P. D., Kessler, G., Lippel, K., Stefanick, M. L., Wasilauskas, C. H., Wells, H. B. 1995; 16 (4): S36-S53

  View details for Web of Science ID A1995RN61200004

• Physical and laboratory measurements in the PEPI Trial Postmenopausal Estrogen/Progestin Interventions. Controlled clinical trials Wood, P. D., Kessler, G., Lippel, K., Stefanick, M. L., Wasilauskas, C. H., Wells, H. B. 1995; 16 (4): 36S-53S

  View details for PubMedID 7587219

• RATIONALE, DESIGN, AND CONDUCT OF THE PEPI TRIAL CONTROLLED CLINICAL TRIALS Espeland, M. A., Bush, T. L., MEBANESIMS, I., Stefanick, M. L., JOHNSON, S., Sherwin, R., Waclawiw, M. 1995; 16 (4): S3-S19

  View details for Web of Science ID A1995RN61200002

• Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions. Controlled clinical trials Espeland, M. A., Bush, T. L., Mebane-Sims, I., Stefanick, M. L., JOHNSON, S., Sherwin, R., Waclawiw, M. 1995; 16 (4): 3S-19S

  Abstract

  There is growing and consistent evidence that estrogen use in postmenopausal women is associated with a substantial reduction in the occurrence of cardiovascular disease. However, remarkably little is known about the biological mechanisms by which estrogen therapy may influence risk. Even less information is available on the cardiovascular effects of combined estrogen-progestin use. PEPI was not designed to test whether estrogen and estrogen-progestin therapy is efficacious in the prevention of cardiovascular disease, as a much larger trial with clinical disease outcomes is needed to answer that question. However, PEPI will provide critical evidence regarding the potential effectiveness of the various estrogen and estrogen/progestin regimens ni altering risk factors for cardiovascular disease in women. Detailed information on factors such as adherence, side effects, and general patient acceptability will also be ascertained. The main results from PEPI will provide the scientific community with information on the basic actions of estrogen and estrogen/progestin therapy on four biological systems believed to be causally associated with cardiovascular disease occurrence. Further, since the trial is designed to continue for 3 years, PEPI will be able to provide information on longer term as well as short-term effects on these systems. Finally, the results from PEPI should enable women and their physicians to select an optimal hormonal regimen, i.e., one that is acceptable, safe, and provides the most beneficial and least deleterious changes in cardiovascular and other risk factors.

  View details for PubMedID 7587218

• LONG-TERM EFFECTS OF VARYING INTENSITIES AND FORMATS OF PHYSICAL-ACTIVITY ON PARTICIPATION RATES, FITNESS, AND LIPOPROTEINS IN MEN AND WOMEN AGED 50 TO 65 YEARS CIRCULATION King, A. C., Haskell, W. L., Young, D. R., Oka, R. K., Stefanick, M. L. 1995; 91 (10): 2596-2604

  Abstract

  Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term, few data are available evaluating their longer-term effects. The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates, fitness, and plasma HDL cholesterol levels among healthy older adults.Higher-intensity, group-based exercise training; higher-intensity, home-based exercise; and lower-intensity, home-based exercise were compared in a 2-year randomized trial. Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease. Recruitment was achieved through a random digit-dial community telephone survey and media promotion. All exercise occurred in community settings. For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate. Treadmill exercise performance, lipoprotein levels and other heart disease risk factors, and exercise adherence were evaluated at baseline and across the 2-year period. Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2, particularly for subjects in the higher-intensity, home-based condition. Subjects in that condition also showed the greatest year 2 exercise adherence rates (P < .003). Although no significant increases in HDL cholesterol were observed during year 1, by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline (P < .01). The increases were particularly pronounced for subjects in the lower-intensity condition, whose exercise prescription required more frequent exercise sessions per week. For all exercise conditions, increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women (P < .04).While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels, the time frame needed to achieve HDL cholesterol change (2 years) may be longer than that reported previously for younger populations. Frequency of participation may be particularly important for achieving such changes. Supervised home-based exercise regimens represent a safe, attractive alternative for achieving sustained participation.

  View details for Web of Science ID A1995QX58700017

  View details for PubMedID 7743622

• EFFECTS OF ESTROGEN OR ESTROGEN/PROGESTIN REGIMENS ON HEART-DISEASE RISK-FACTORS IN POSTMENOPAUSAL WOMEN - THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS (PEPI) TRIAL JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Miller, V. T., LaRosa, J., Barnabei, V., Kessler, C., Levin, G., SMITHROTH, A., Griffin, M., Stoy, D. B., Bush, T., Zacur, H., Foster, D., Anderson, J., McKenzie, A., Miller, S., Wood, P. D., Stefanick, M. L., Marcus, R., AKANA, A., Heinrichs, L., Kirchner, C., OHANLAN, K., Ruyle, M., Sheehan, M., Judd, H. L., Greendale, G., BAYALOS, R., Lozano, K., Kawakami, K., BARRETTCONNOR, E., Langer, R., KRITZSILVERSTEIN, D., CARRIONPETERSEN, M. L., CAVERO, C., Schrott, H. G., Johnson, S. R., FEDDERSEN, D. A., KRUTZFELDT, D. L., Benda, J. A., PAUERSTEIN, C., Trabal, J., Schenken, R., Stern, M. P., RODRIGUEZSIFUENTES, M., Easton, C., Wells, H. B., Espeland, M., Howard, G., Byington, R., Legault, C., Shumaker, S., Hogan, P., HIRE, D., Wasilauskas, C., James, M., Lane, K., Terrell, T., Reece, S., Pierce, J., Snow, M., Anthony, S., MEBANESIMS, I. L., Einhorn, P., Hunsberger, S., Waclawiw, M., Lippel, K., Lucas, D., Verter, J., Jackson, S., Kelaghan, J., Perlman, J., Wolf, P., McGowan, J., GORDON, S., Heyse, S., Fradkin, J., Sherman, S., Page, L., Sorenson, A., Hulka, B., Brody, B., Burkman, R., Heaney, R., Krauss, R., Roberts, H., Wittes, J., Riggs, L., Moss, R., Albers, J., Marcovina, S., Fineberg, S. E., Tracy, R. P., Merino, M., Scully, R., Livolsi, V., Kessler, G. 1995; 273 (3): 199-208

  Abstract

  To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women.A 3-year, multicenter, randomized, double-blind, placebo-controlled trial.A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy.Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. PRIMARY ENDPOINTS: Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen.Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment.Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dL]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status.Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia.

  View details for Web of Science ID A1995QB23400023

• THE EFFECTS OF WEIGHT-LOSS BY EXERCISE OR BY DIETING ON PLASMA HIGH-DENSITY-LIPOPROTEIN (HDL) LEVELS IN MEN WITH LOW, INTERMEDIATE, AND NORMAL-TO-HIGH HDL AT BASE-LINE METABOLISM-CLINICAL AND EXPERIMENTAL Williams, P. T., Stefanick, M. L., Vranizan, K. M., Wood, P. D. 1994; 43 (7): 917-924

  Abstract

  To assess whether baseline plasma high-density lipoprotein (HDL) cholesterol levels affected the HDL response to weight loss, we examined lipoprotein changes in overweight men aged 30 to 59 years who were randomized to lose weight by exercise training (primarily running, n = 46) or by caloric restriction (ie, dieting, n = 42) or to remain sedentary, nondieting controls (n = 42) in a 1-year study. In exercisers, absolute increases in HDL (mg/dL) were greatest in men with normal-to-high baseline HDL and least in men with low baseline HDL. Specifically, when divided into groups of low (< or = 37 mg/dL), intermediate (38 to 47 mg/dL), and normal-to-high HDL cholesterol (> or = 48 mg/dL) at baseline, the exercisers increased HDL cholesterol by 2.3 +/- 1.9, 4.9 +/- 1.1, and 7.0 +/- 1.3 mg/dL, respectively; HDL2 cholesterol by 0.8 +/- 1.6, 2.3 +/- 1.2, and 5.1 +/- 1.3 mg/dL; and HDL2 mass by 2.8 +/- 5.1, 9.5 +/- 8.9, and 31.7 +/- 11.0 mg/dL. Relative increases in HDL cholesterol were more similar in the low (7.1% +/- 6.1%), intermediate (12.4% +/- 3.9%), and normal-to-high men (13.2% +/- 4.0%). Regression analyses were performed to assess whether baseline HDL cholesterol was related to the amount of absolute HDL change per unit of weight loss. In exercisers, the increase in HDL3 cholesterol concentrations was significantly greater in men with low HDL than in those with normal-to-high HDL at entry (2.0 +/- 0.8 v 0.2 +/- 0.8 mg/dL per kg/m2 lost).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1994NV98400022

  View details for PubMedID 8028519

• EFFECTS OF LOW-FAT DIET, CALORIE RESTRICTION, AND RUNNING ON LIPOPROTEIN SUBFRACTION CONCENTRATIONS IN MODERATELY OVERWEIGHT MEN METABOLISM-CLINICAL AND EXPERIMENTAL Williams, P. T., Krauss, R. M., Stefanick, M. L., Vranizan, K. M., Wood, P. D. 1994; 43 (5): 655-663

  Abstract

  We studied the effects of exercise (primarily running), calorie restriction (dieting), and a low-fat, high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a randomized controlled clinical trial. After 1 year, complete data were obtained for 39 men assigned to lose weight through dieting without exercise, 37 men assigned to lose weight through dieting with exercise (primarily running), and 40 nondieting sedentary controls. We instructed both diet groups to consume no more than 30% total fat, 10% saturated fat, and 300 mg/d of cholesterol, and at least 55% carbohydrates, and the controls were instructed to maintain their usual food choices. Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations. In addition, the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein (HDL) subclasses that have been identified by their particle sizes, ie, HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Relative to controls, weight decreased significantly in men who dieted with exercise (net difference +/- SE, -3.3 +/- 0.4 kg/m2) and in men who dieted without exercise (-2.0 +/- 0.4 kg/m2). Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass, HDL3a, HDL2a, and HDL2b relative to both control and dieting without exercise. There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1994NL24400021

  View details for PubMedID 8177056

• Exercise and weight control. Exercise and sport sciences reviews Stefanick, M. L. 1993; 21: 363-396

  Abstract

  Several important questions need to be answered to increase the likelihood that exercise will be accepted by the millions in the population who are obese. What is the minimum exercise "dose" (intensity, duration, frequency) and what is the optimal mode to bring about substantial fat weight loss, with minimal loss of lean mass? What is the best nutritional plan to optimize fat utilization during exercise, without impairing performance or loss of lean mass? Which diet and exercise programs maximally increase utilization of centrally deposited fat and how can hyperplastic obesity best be treated? Also of interest is the potential role of resistance exercise for weight loss, and the predictors of weight loss success. For instance, do individuals with gynoid obesity really differ from individuals with android obesity in their utilization and loss of body fat during exercise? The potential advantages of exercise include: stimulation of fat as opposed to carbohydrate oxidation; increased energy use during the exercise itself and in the postexercise period; protection of lean body mass; possible reversal of the diet-induced suppression of BMR; and other health benefits. Among other parameters, the effectiveness of exercise on weight loss may be influenced by the type, intensity, frequency, and duration of exercise bouts and the duration of the training program, the nature of the excess fat stores, i.e., whether the person has obesity characterized by hyperplastic or hypertrophic adipose tissue or central (with large-intra-abdominal depot) or peripheral obesity, the composition and caloric content of the diet, and behavioral aspects that affect adherence to the program. With respect to this latter concern, even if a person has been very successful at weight loss in a metabolic ward or intensive program, he/she must eventually return to the outside world and figure out for himself/herself how to eat real food and/or maintain an activity level that promotes weight maintenance. Because diet and exercise habits are difficult to assess and to quantify in free-living populations, it continues to be difficult to evaluate the success of diet and/or exercise prescriptions for weight loss accurately and we continue to be plagued with questions regarding the effectiveness vs. efficacy of exercise as a means to control body weight. It would seem that the wide range of health benefits derived from regular exercise would justify emphasizing increased activity for inactive people, particularly for obese, sedentary individuals, whether or not ideal body weight or significant weight loss is achieved.

  View details for PubMedID 8504848

• ASSOCIATIONS OF LIPOPROTEINS AND APOLIPOPROTEINS WITH GRADIENT GEL-ELECTROPHORESIS ESTIMATES OF HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS IN MEN AND WOMEN ARTERIOSCLEROSIS AND THROMBOSIS Williams, P. T., Krauss, R. M., Vranizan, K. M., Stefanick, M. L., WOOD, P. D., LINDGREN, F. T. 1992; 12 (3): 332-340

  Abstract

  We examined the relations of gender and lipoproteins to subclasses of high density lipoproteins (HDLs) in a cross-sectional sample of moderately overweight men (n = 116) and women (n = 78). The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations of HDL at intervals of 0.01 nm across the entire HDL particle size range (7.2-12 nm). At least five HDL subclasses have been identified by their particle sizes: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Men had significantly higher HDL3b and significantly lower HDL2a and HDL2b than did women. Correlations of HDL subclasses with concentrations of other lipoprotein variables were generally as strong for gradient gel electrophoresis as for analytical ultracentrifugation measurements of HDL particle distributions. In both sexes, high levels of HDL3b were associated with coronary heart disease risk factors, including high concentrations of triglycerides, apolipoprotein B, small low density lipoproteins, intermediate density lipoproteins, and very low density lipoproteins and low concentrations of HDL2 cholesterol and HDL2 mass. Plasma concentrations of HDL3 cholesterol were unrelated to protein-stained HDL3b levels. HDL3 cholesterol concentrations also did not exhibit the sex difference or the relations with lipoprotein concentrations that characterized HDL3b. Thus, low HDL3b levels may contribute in part to the low heart disease risk in men and women who have high HDL cholesterol. Measurements of HDL3 cholesterol may not identify clinically important relations involving HDL3b.

  View details for Web of Science ID A1992HJ91600010

  View details for PubMedID 1547192

• HORMONES AND SEXUAL-BEHAVIOR IN RELATIONSHIP TO AGING IN MALE-RATS HORMONES AND BEHAVIOR Smith, E. R., Stefanick, M. L., Clark, J. T., DAVIDSON, J. M. 1992; 26 (1): 110-135

  Abstract

  To determine if the age-related decline in male sex behavior is correlated with hormonal factors, a longitudinal study was conducted. Sexually experienced males were given mating tests every 2 months from 7 through 27 months of age. To study possible relationships between changes in behavior and alterations in hormone levels, blood samples were taken before and after these bimonthly tests. At 23 months, cross-sectional studies were also conducted comparing results to those obtained in 5-month-old males. Significant changes in mating behavior first appeared at 11 months; mount latency, intromission latency, ejaculation latency, postejaculatory interval, and intercopulatory interval were increased. Similarly, detectable decreases in testosterone (T) also occurred at this age. A significant decline in luteinizing hormone (LH) was not seen until 19 months. Correlational analyses revealed small (r less than or equal to -0.29) but significant negative correlations between T and parameters of mating behavior with age. When each age was examined separately, no significant correlations appeared. Plasma T was not predictive of behavioral performance. At 23 months, cross-sectional studies revealed deficits in mounting and penile reflex behavior but ejaculatory reflex capacity was unimpaired. At 28 months, males were decapitated. Only T levels showed a significant effect of age; estradiol, prolactin, and LH were unaffected when compared to 5-month-old males. The data suggest that although there are small and significant negative correlations between circulating testosterone and parameters of mating behavior with advancing age, it is unlikely that the observed decline in testosterone is the primary cause of the age-induced behavioral deficits. It is likely that the major causal factor(s) involves non-hormone-dependent changes within the CNS.

  View details for Web of Science ID A1992HJ94600009

  View details for PubMedID 1563724

• THE EFFECTS ON PLASMA-LIPOPROTEINS OF A PRUDENT WEIGHT-REDUCING DIET, WITH OR WITHOUT EXERCISE, IN OVERWEIGHT MEN AND WOMEN NEW ENGLAND JOURNAL OF MEDICINE Wood, P. D., Stefanick, M. L., Williams, P. T., Haskell, W. L. 1991; 325 (7): 461-466

  Abstract

  The National Cholesterol Education Program (NCEP) recommends a low-saturated-fat, low-cholesterol diet, with weight loss if indicated, to correct elevated plasma cholesterol levels. Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein (HDL) cholesterol. Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people.We tested the hypothesis that exercise (walking or jogging) will increase HDL cholesterol levels in moderately overweight, sedentary people who adopt a hypocaloric NCEP diet. We randomly assigned 132 men and 132 women 25 to 49 years old to one of three groups: control, hypocaloric NCEP diet, or hypocaloric NCEP diet with exercise. One hundred nineteen of the men and 112 of the women returned for testing after one year.After one year, the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly (range of reduction in mean fat weight, 4.0 to 7.8 kg). Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group. Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted (mean [+/- SE] change, +13 +/- 3 percent) than in the men who only dieted (+2 +/- 3 percent, P less than 0.01) or the men who acted as controls (-4 +/- 2 percent, P less than 0.001). HDL cholesterol levels remained about the same in the women who exercised and dieted (+1 +/- 2 percent); they were higher than in the women who only dieted (-10 +/- 3 percent, P less than 0.01), but not higher than in the controls (-3 +/- 3 percent).Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat, low-cholesterol diet.

  View details for Web of Science ID A1991GA76300003

  View details for PubMedID 1852180

• CONTRIBUTIONS OF REGIONAL ADIPOSE-TISSUE DEPOTS TO PLASMA-LIPOPROTEIN CONCENTRATIONS IN OVERWEIGHT MEN AND WOMEN - POSSIBLE PROTECTIVE EFFECTS OF THIGH FAT METABOLISM-CLINICAL AND EXPERIMENTAL Terry, R. B., Stefanick, M. L., Haskell, W. L., Wood, P. D. 1991; 40 (7): 733-740

  Abstract

  Anthropometry and dual-photon absorptiometry (DPA) were used to examine associations of regional adiposity with plasma lipid, lipoprotein, and lipoprotein subfraction mass concentrations in moderately overweight men and women. Among 130 women, waist to thigh girth ratio (WTR) correlated with triglycerides (TG) (r = .33, P less than .0001) and negatively with high-density lipoprotein (HDL)-cholesterol (HDL-C) (r = -.37, P less than .0001) concentration, as expected. While WTR did not correlate with low-density lipoprotein (LDL)-cholesterol (LDL-C) it correlated positively with the mass subfraction of small (Sfo, 0 to 7) LDL (r = .38, P less than .0001), and negatively with large (Sfo, 7 to 12) LDL (r = -.31, P less than .01). Among 133 men, similar though weaker relationships were found. Thigh girth correlated positively with HDL and HDL2-C and mass, and with LDL particle size among women. Multivariate analysis suggests that association of WTR with lipoprotein values known to carry risk of coronary heart disease (CHD) are due at least as much to effects of thigh girth as to deleterious effects of waist girth. Estimates of fat weight in thigh and abdominal regions by DPA support thigh fat as contributing to these effects of thigh girth. Thigh fat may contribute to lipoprotein profiles that predict lower risk of cardiovascular disease.

  View details for Web of Science ID A1991FV09000014

  View details for PubMedID 1870428

• INSULIN RESISTANCE AND HYPERTRIGLYCERIDEMIA IN NONDIABETIC RELATIVES OF PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Laws, A., Stefanick, M. L., Reaven, G. M. 1989; 69 (2): 343-347

  Abstract

  Plasma glucose, FFA, and insulin responses to an oral glucose challenge, plasma lipid and lipoprotein concentrations, and the ability of insulin to stimulate glucose disposal were measured in 35 nondiabetic sedentary and overweight subjects. The subjects were divided into 2 groups on the basis of the presence (n = 19) or absence (n = 16) of a history of a first degree relative with noninsulin-dependent diabetes. The 2 groups were similar in age, body mass index, waist to hip ratio, and maximal aerobic capacity. The results demonstrated that the ability of insulin to stimulate disposal of a glucose load was significantly reduced in the subjects with a positive family history of noninsulin-dependent diabetes. In addition, these individuals had significantly higher plasma triglyceride and very low density lipoprotein cholesterol concentrations. Since all environmental factors known to modify insulin action and very low density lipoprotein metabolism were equal in the 2 groups, these data suggest that the metabolic differences noted are likely to be genetic in origin.

  View details for Web of Science ID A1989AF97500020

  View details for PubMedID 2666429

• REGIONAL ADIPOSITY PATTERNS IN RELATION TO LIPIDS, LIPOPROTEIN CHOLESTEROL, AND LIPOPROTEIN SUBFRACTION MASS IN MEN JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Terry, R. B., Wood, P. D., Haskell, W. L., Stefanick, M. L., Krauss, R. M. 1989; 68 (1): 191-199

  Abstract

  Anatomical adipose tissue distribution patterns are reported to relate to plasma lipids and risk of cardiovascular disease. Waist to hip girth ratios (WHR) and subscapular 10 triceps skinfold thickness ratios (STR) were compared with percent body fat and body mass index values as correlates of plasma lipids and lipoprotein cholesterol and serum lipoprotein subfraction mass by analytic ultracentrifugation in 81 sedentary middle-aged men in a typical range of adiposity. WHR was significantly and positively correlated with plasma concentrations of triglycerides, cholesterol, and low and very low density lipoprotein (LDL and VLDL) cholesterol and inversely correlated with high density lipoprotein (HDL) cholesterol. STR followed these trends, though less strongly, in relation to plasma triglycerides, VLDL cholesterol, and HDL cholesterol. Pronounced differences were found between regional adiposity patterns in their relationships to lipoprotein subfractions, as determined by analytic ultracentrifugation. WHR was negatively correlated with HDL2 (flotation rate F(1.2) 3.5-9), positively with small LDL (S.f 0-7), intermediate density lipoprotein (S.f 12-20), and VLDL (S.f 20-400), while STR correlated with larger LDL (S.f 7-12) and larger VLDL (S.f 60-400). Overall adiposity was not significantly associated with plasma lipoprotein levels after adjusting for regional adiposity patterns. Plasma sex hormone-binding globulin and percent free testosterone were associated with regional adiposity, but did not account for the correlations between WHR and lipoproteins. WHR and STR are measures of fat distribution that correlate with plasma lipoprotein profiles consistent with cardiovascular disease risk and have different relationships to lipoprotein mass subfractions.

  View details for Web of Science ID A1989R678200031

  View details for PubMedID 2909551

• CHANGES IN PLASMA-LIPIDS AND LIPOPROTEINS IN OVERWEIGHT MEN DURING WEIGHT-LOSS THROUGH DIETING AS COMPARED WITH EXERCISE NEW ENGLAND JOURNAL OF MEDICINE Wood, P. D., Stefanick, M. L., Dreon, D. M., FREYHEWITT, B., GARAY, S. C., Williams, P. T., Superko, H. R., Fortmann, S. P., Albers, J. J., Vranizan, K. M., ELLSWORTH, N. M., Terry, R. B., Haskell, W. L. 1988; 319 (18): 1173-1179

  Abstract

  We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men--decreasing energy intake without increasing exercise (diet), and increasing energy expenditure without altering energy intake (exercise, primarily running)--in a one-year randomized controlled trial. As compared with controls (n = 42), dieters (n = 42) had significant loss of total body weight (-7.8 +/- 0.9 kg [mean +/- SE]), fat weight (-5.6 +/- 0.8 kg), and lean (non-fat) weight (-2.1 +/- 0.5 kg) (P less than 0.001 for each variable), and exercisers (n = 47) had significant loss of total body weight (-4.6 +/- 0.8 kg) and fat weight (-3.8 +/- 0.7 kg) (P less than 0.001 for both variables) but not lean weight (-0.7 +/- 0.4 kg). Fat-weight loss did not differ significantly between dieters and exercisers. All subjects were discouraged from altering their diet composition; however, dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat. As compared with the control group, both weight-loss groups had significant increases (P less than 0.01) in plasma concentrations of high-density lipoprotein (HDL) cholesterol (diet vs. exercise, 0.13 +/- 0.03 vs. 0.12 +/- 0.03 mmol per liter), HDL2 cholesterol (0.07 +/- 0.02 vs. 0.07 +/- 0.02 mmol per liter), and HDL3 cholesterol (0.07 +/- 0.02 vs. 0.06 +/- 0.02 mmol per liter) and significant decreases (P less than 0.05) in triglyceride levels (diet vs. exercise, -0.35 +/- 0.14 vs. -0.24 +/- 0.12 mmol per liter). Levels of total and low-density lipoprotein cholesterol were not significantly changed, relative to values in controls. None of these changes were significantly different between dieters and exercisers. Thus, we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations.

  View details for Web of Science ID A1988Q697500001

  View details for PubMedID 3173455

• THE EFFECT OF ACTIVE WEIGHT-LOSS ACHIEVED BY DIETING VERSUS EXERCISE ON POSTHEPARIN HEPATIC AND LIPOPROTEIN-LIPASE ACTIVITY ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Stefanick, M. L., FREYHEWITT, B., Hoover, C. A., Terry, R. B., Wood, P. D. 1987; 499: 338-339

  View details for Web of Science ID A1987J506700038

• RELATIONSHIPS OF PLASMA ESTRADIOL, TESTOSTERONE, AND SEX HORMONE-BINDING GLOBULIN WITH LIPOPROTEINS, APOLIPOPROTEINS, AND HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS IN MEN JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Stefanick, M. L., Williams, P. T., Krauss, R. M., Terry, R. B., Vranizan, K. M., Wood, P. D. 1987; 64 (4): 723-729

  Abstract

  Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

  View details for Web of Science ID A1987G463100014

  View details for PubMedID 3818901

• GENITAL RESPONSES IN NONCOPULATORS AND RATS WITH LESIONS IN THE MEDIAL PREOPTIC AREA OR MIDTHORACIC SPINAL-CORD PHYSIOLOGY & BEHAVIOR Stefanick, M. L., DAVIDSON, J. M. 1987; 41 (5): 439-444

  Abstract

  To determine whether genital dysfunction participates in the sexual inactivity of noncopulator and MPOA-lesioned rats, penile reflexes and spontaneous seminal emission (SSE) were investigated in such animals. The display of penile reflexes was either the same or enhanced in these animals, relative to controls. Noncopulators and MPOA-lesioned rats also did not differ from controls in SSE. Plasma testosterone levels showed no differences between noncopulators and sexually active controls but tended to be elevated in rats bearing MPOA lesions. Finally, SSE did not differ between rats with midthoracic spinal cord transections and controls, suggesting that SSE is not under supraspinal inhibition.

  View details for Web of Science ID A1987K989300008

  View details for PubMedID 3432397

• REPRODUCTIVE PHYSIOLOGY AND BEHAVIOR IN THE MALE-RAT FOLLOWING ACUTE AND CHRONIC PERIPHERAL ADRENERGIC DEPLETION BY GUANETHIDINE PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Stefanick, M. L., Smith, E. R., SZUMOWSKI, D. A., DAVIDSON, J. M. 1985; 23 (1): 55-63

  Abstract

  The effect of guanethidine, an adrenergic neuron blocking agent, on sexual behavior, penile reflexes, and spontaneous seminal emission (SSE) in the rat was studied by acute (i.e., 4 hours prior to testing) and daily IP injection of a low (5 mg/kg) and moderately high (25 mg/kg) dose of the drug. Acute low dose treatment eliminated the expulsion of a seminal plug with behavioral ejaculation without affecting sexual behavior; while acute high dose administration significantly decreased the number of intromissions preceding ejaculation and eliminated emission in copula and SSE for 3 days, with no evidence of retrograde ejaculation. Acute high dose treatment also increased the number of long flips displayed in the penile reflex test, and resulted in significant depression in plasma testosterone (T) and luteinizing hormone (LH) levels. Daily injection with the low dose eliminated emission in and ex copula for 4 weeks, without altering sexual behavior or penile reflexes. Seminal emission in copula reappeared more rapidly after stopping injections than SSE. Chronic high dose treatment was also without effect on copulatory activity. There was a partial recovery of emission in copula by the fourth week of treatment, suggesting that a nonadrenergic mechanism had assumed this function. In penile reflex tests conducted after 4 and 8 weeks, significantly fewer erections were displayed by drug-treated animals. During the period of initial recovery of emission in copula, emission during the reflex test was markedly increased, but SSE was decreased. Plasma T was significantly suppressed after two and four weeks of daily injections, but not thereafter, while plasma LH levels were not affected by the drug.

  View details for Web of Science ID A1985ANQ1800011

  View details for PubMedID 4034620

• RELATIONSHIP BETWEEN PLASMA LIPOPROTEINS (LP) AND SEX-HORMONES IN MEN BEFORE AND AFTER EXERCISE TRAINING Stefanick, M. L., Williams, P. T., DAVIDSON, J. M., Krauss, R. M., Wood, P. D. FEDERATION AMER SOC EXP BIOL. 1985: 847–47

  View details for Web of Science ID A1985ADF6102586

• THE CIRCADIAN PATTERNS OF SPONTANEOUS SEMINAL EMISSION, SEXUAL-ACTIVITY AND PENILE REFLEXES IN THE RAT PHYSIOLOGY & BEHAVIOR Stefanick, M. L. 1983; 31 (6): 737-743

  Abstract

  Spontaneous seminal emission (SSE) by sexually naive and experienced rats occurred almost exclusively in the light period of a 14:10 LD cycle. The circadian pattern of SSE slowly shifted following an LD reversal and was completely reversed by three weeks. The diurnal variation in parameters of sexual activity which are associated with sexual arousal shifted much more readily such that it was reversed within one week of the LD reversal. In contract, parameters of sexual behavior which are associated with the ejaculatory mechanism were altered following the LD shift with a phase-shifting pattern more similar to that exhibited for SSE, such that the diurnal variation seen before the LD shift was not reestablished until the third week after the shift. The characteristic pattern of SSE in 14:10 LD lighting was disrupted with two weeks of a shift to constant illumination, but the number and weight of spontaneously produced plugs did not change. Finally, there were no differences in any component of the display of penile reflexes by 29 rats tested in the dark period compared to 19 rats tested in the light period, despite significant circadian variation in the copulatory activity of these animals.

  View details for Web of Science ID A1983RS83800001

  View details for PubMedID 6665062

• PENILE REFLEXES IN INTACT RATS FOLLOWING ANESTHETIZATION OF THE PENIS AND EJACULATION PHYSIOLOGY & BEHAVIOR Stefanick, M. L., Smith, E. R., DAVIDSON, J. M. 1983; 31 (1): 63-65

  Abstract

  Application of the topical anesthetic pontocaine (tetracaine hydrochloride) to the penis and preputial sheath virtually abolished the display of penile reflexes by intact rats. When pontocaine was applied immediately following ejaculation in copula, however, normal genital reflexes were observed in the majority of rats, albeit with a prolonged latency to the first erection relative to the control test. These same animals were, nonetheless, unable to achieve intromission when returned to the mating arena despite repeated mounting attempts. These data suggest that sensory input to the genitalia is generally necessary for the display of penile reflexes in the rat. However, stimuli associated with copulation can override the suppressive effect of sensory loss of these reflexes, presumably due to removal of supraspinal inhibition.

  View details for Web of Science ID A1983RB04000009

  View details for PubMedID 6634978

• FURTHER-STUDIES ON ALTERATIONS IN MALE-RAT COPULATORY-BEHAVIOR INDUCED BY THE DOPAMINE-RECEPTOR AGONIST RDS-127 PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR Clark, J. T., Stefanick, M. L., Smith, E. R., DAVIDSON, J. M. 1983; 19 (5): 781-786

  Abstract

  Pharmacologic dopamine receptor stimulation by RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane) resulted in qualitatively different changes in the mating pattern depending on the dose administered and time elapsed between treatment and behavioral observation. A low dose (0.25 mg/kg) selectively increased the latency to ejaculation whereas a high dose (3.0 mg/kg) decreased ejaculation latency and intromission frequency (both indicators of ejaculatory efficiency) when behavioral observations were begun 30 minutes after intraperitoneal administration. Intermediate doses (0.5, 1.0, and 2.0 mg/kg) did not alter the time required to achieve ejaculation but did lower the number of intromissions preceding ejaculation. These dose-dependent actions resemble the effects of dopaminomimetics (reported by others) on locomotor activity. When mating tests were conducted shortly (less than five minutes) after drug administration, the induction of ejaculation by the high dose was enhanced. At this time, as well as after a prolonged delay (two hours), signs of decreased arousal (longer intromission latencies) were also observed. However, the postejaculatory refractory period was altered in a time-dependent fashion, viz: it was shortened closest to the injection time, not altered 30 minutes after treatment, and increased two hours after RDS-127 administration. Finally, RDS-127 induced seminal emission (ex copula) in 2.9 +/- 0.9 (S.E.) minutes, and these emissions did not differ in weight from normal spontaneous (diurnal) seminal emissions. The RDS-127-induced seminal emission was not followed by a refractory period of similar magnitude to that seen after ejaculation in copula. The data are interpreted in terms of the involvement of dopamine receptor subtypes in the modulation of masculine sexual behavior.

  View details for Web of Science ID A1983RQ84000010

  View details for PubMedID 6647512

• SEXUAL EXPERIENCE AND PLASMA TESTOSTERONE LEVELS IN MALE VETERANS AFTER SPINAL-CORD INJURY ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Phelps, G., Brown, M., Chen, J., Dunn, M., Lloyd, E., Stefanick, M. L., DAVIDSON, J. M., Perkash, I. 1983; 64 (2): 47-52

  Abstract

  Fifty men with spinal cord injuries (SCI) were asked to complete a questionnaire concerning their sexuality before and after injury. Medical examination confirmed the location and completeness of the injury and extracted information about genitourologic status. The respondents rated sexuality highly as a concern in living, and a wide variety of sexual techniques were reported. A marked decrease in sexual activity, satisfaction, and feelings of sexual adequacy was reported after injury, as compared to retrospective "before injury" responses, lack of opportunity being reported as causative by 66% of the subjects and insufficient personal satisfaction by 59%. Seventy-five percent of the subjects experienced sexual arousal from genital stimulation, and several methods of eliciting erection were cited. Orgasm was described by a variety of terms. Significant differences were found between quadriplegic and paraplegic patients in answers to several items, though there was generally no difference between cervical and thoracic groups, which were more specifically broken down with respect to motor or sensory/complete or incomplete lesions. Plasma testosterone levels were found to fall well within the normal adult male range, as were levels of free testosterone and serum sex binding protein. The resulting information demonstrated more sexual concern among men with SCI than the literature previously indicated.

  View details for Web of Science ID A1983QB70600001

  View details for PubMedID 6681699

• EFFECTS OF A NOVEL DOPAMINE-RECEPTOR AGONIST RDS-127 (2-N,N-DI-N-PROPYLAMINO-4,7-DIMETHOXYINDANE), ON HORMONE LEVELS AND SEXUAL-BEHAVIOR IN THE MALE-RAT PHYSIOLOGY & BEHAVIOR Clark, J. T., Smith, E. R., Stefanick, M. L., Arneric, S. P., Long, J. P., DAVIDSON, J. M. 1982; 29 (1): 1-6

  Abstract

  Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.

  View details for Web of Science ID A1982NX40200001

  View details for PubMedID 7122715

• EFFECTS OF A POTENT DOPAMINE RECEPTOR AGONIST, RDS-127, ON PENILE REFLEXES AND SEMINAL EMISSION IN INTACT AND SPINALLY TRANSECTED RATS PHYSIOLOGY & BEHAVIOR Stefanick, M. L., Smith, E. R., Clark, J. T., DAVIDSON, J. M. 1982; 29 (6): 973-978

  Abstract

  Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.

  View details for Web of Science ID A1982PS53000001

  View details for PubMedID 7163401

• ROLE OF ANDROGEN IN SEXUAL REFLEXES OF MALE RAT PHYSIOLOGY & BEHAVIOR DAVIDSON, J. M., Stefanick, M. L., Sachs, B. D., Smith, E. R. 1978; 21 (2): 141-146

  View details for Web of Science ID A1978FN17000001

  View details for PubMedID 693640