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 PARTICIPANTS: A 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 oakleys Australia stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death.RESULTS: 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, Oakley Australia 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.CONCLUSIONS AND RELEVANCE: Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention oakley Holbrook 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.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.Comment inThe Women\'s Health Initiative--a victory for women and their health. [JAMA. 2013]The Women\'s Health Initiative--a victory for women and their health.Nabel EG. JAMA. 2013 Oct 2; 310(13):1349-50. Reproductive endocrinology: oakley Frogskins Hormone therapy to treat menopause--breaking a taboo. [Nat Rev Endocrinol. 2014]Reproductive endocrinology: Hormone therapy to treat menopause--breaking a taboo.Davis SR. Nat Rev Endocrinol. 2014 Jan; 10(1):6-8. Epub 2013 Oct 29.Menopausal hormone therapy and prevention of chronic diseases: IMS members react to the recent JAMA paper. [Climacteric. 2014]Menopausal hormone therapy and prevention of chronic diseases: IMS members react to the recent JAMA paper.Hodis HN, Neves-e-Castro M. Climacteric. 2014 Feb; 17(1):99-101. Hormone therapy use and outcomes in the Women\'s Health Initiative trials--reply. [JAMA. 2014]Hormone therapy use and outcomes in the Women\'s Health Initiative trials--reply.Manson JE, Chlebowski RT, Aragaki AK. JAMA. 2014 Jan 22-29; 311(4):417-8. Hormone therapy use and outcomes in the Women\'s Health Initiative trials. [JAMA. 2014]Hormone therapy use and outcomes in the Women\'s Health Initiative trials.Roehm E. JAMA. 2014 Jan 22-29; 311(4):417. Menopausal hormone therapy has risks and benefits during the intervention and poststopping phase. [Evid Based Med. 2014]Menopausal hormone therapy has risks and benefits during the intervention and poststopping phase.Warren MP. Evid Based Med. 2014 Jun; 19(3):105. Epub 2014 Feb 3.