IMPORTANCE Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.OBJECTIVE To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up. DESIGN, SETTING, AND PARTICIPANTSA total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. INTERVENTIONS 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.MAIN OUTCOMES AND MEASURES 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. RESULTSDuring 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 Ն65 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.CONCLUSIONS AND RELEVANCE 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 n...

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.

This report provides a further analysis of the year 4 weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with long-term success. A total of 5145 overweight/obese men and women with type 2 diabetes were randomly assigned to an intensive lifestyle intervention (ILI) or a usual care group, referred to as Diabetes Support and Education (DSE). ILI participants were provided approximately weekly group or individual treatment in year 1; continued but less frequent contact was provided in years 2–4. DSE participants received three group educational sessions in all years. As reported previously, at year 4, ILI participants lost an average of 4.7% of initial weight, compared with 1.1% for DSE (p<0.0001). More ILI than DSE participants lost ≥5% (46% vs 25%, p<0.0001) and ≥10% (23% vs 10%, p<0.0001) of initial weight. Within the ILI, acheivement of both the 5% and 10% categorical weight losses at year 4 was strongly related to meeting these goals at year 1. A total of 887 participants in ILI lost ≥10% at year 1, of whom 374 (42.2%) achieved this loss at year 4. Participants who maintained the loss, compared with those who did not, attended more treatment sessions and reported more favorable physical activity and food intake at year 4. These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., ≥5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years.

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.

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.