Abstract/Text: CONTEXT: 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.
OBJECTIVE: To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.
DESIGN, SETTING, AND PARTICIPANTS: 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.
MAIN OUTCOME MEASURES: 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.
RESULTS: 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.
CONCLUSIONS: 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.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

Abstract/Text: There are many options available to address the quality of life and health concerns of menopausal women. The principal indication for hormone therapy (HT) is the treatment of vasomotor symptoms, and benefits generally outweigh risks for healthy women with bothersome symptoms who elect HT at the time of menopause. Although HT increases the risk of coronary heart disease, recent analyses confirm that this increased risk occurs principally in older women and those a number of years beyond menopause. These findings do not support a role for HT in the prevention of heart disease but provide reassurance regarding the safety of use for hot flushes and night sweats in otherwise healthy women at the menopausal transition. An increased risk of breast cancer with extended use is another reason short-term treatment is advised. Hormone therapy prevents and treats osteoporosis but is rarely used solely for this indication. If only vaginal symptoms are present, low-dose local estrogen therapy is preferred. Contraindications to HT use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease. Alternatives to HT should be advised for women with or at increased risk for these disorders. The lowest effective estrogen dose should be provided for the shortest duration necessary because risks increase with increasing age, time since menopause, and duration of use. Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences.