This systematic evidence review is an update for the U.S. Preventive Services Task Force (USPSTF) recommendations on use of menopausal hormone therapy for postmenopausal women to prevent chronic health conditions such as cardiovascular disease, types of cancer, and osteoporotic fractures. Use of menopausal hormone therapy for treatment of menopausal symptoms, such as vasomotor hot flashes or urogenital atrophy, or for other indications is outside the scope of this review. Menopausal hormone therapy includes use of various forms, doses, and regimens of estrogen with or without progestin. Estrogen combined with progestin is used by women who have not had previous hysterectomies to prevent endometrial proliferation and endometrial cancer, whereas women with previous hysterectomies use estrogen only. In 2002, the USPSTF recommended against the routine use of combined estrogen and progestin hormone therapy for the prevention of chronic conditions in postmenopausal women who have not had hysterectomies because the harmful effects were likely to exceed the chronic disease prevention benefits in most women (D recommendation). Based on the results of systematic reviews3-11 and early findings of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the USPSTF found good evidence that combined hormone therapy results in both benefits and harms. Benefits included reduced risk for fracture (good evidence) and colorectal cancer (fair evidence). Combined estrogen and progestin had no beneficial effect on coronary heart disease and suggested an increased risk (good evidence). Other harms included increased risk for breast cancer (good evidence), venous thromboembolism (good evidence), stroke (fair evidence), cholecystitis (fair evidence), dementia (fair evidence), and lower global cognitive function (fair evidence). Because of insufficient evidence, the USPSTF could not assess effects on the incidence of ovarian cancer, mortality from breast cancer or coronary heart disease, or all-cause mortality.In 2005, the USPSTF recommended against the routine use of unopposed estrogen for the prevention of chronic conditions in postmenopausal women who have had previous hysterectomies based on results of the WHI trial of estrogen only in women with hysterectomies (D recommendation). The USPSTF found good evidence that the use of unopposed estrogen resulted in both benefits and harms. The benefits included reduced risk for fracture (good evidence), and harms included increased risk for venous thromboembolism (fair evidence), stroke (fair evidence), dementia (fair evidence), and lower global cognitive function (fair evidence). There was fair evidence that unopposed estrogen had no beneficial effect on coronary heart disease. The USPSTF could not assess the effects of unopposed estrogen on the incidence of breast cancer, ovarian cancer, or colorectal cancer, as well as breast cancer mortality or all-cause mortality. A standard protocol was developed and followed for this review. Based on evidence from the previous review and using the methods of the USPSTF, USPSTF members and Agency for Healthcare Research and Quality (AHRQ) scientific staff determined the key questions for this update. Investigators created an analytic framework incorporating the key questions and outlining the patient populations, interventions, outcomes, and harms of menopausal hormone therapy. Key questions include: 1. What are the benefits of menopausal hormone therapy when used to prevent chronic conditions? 2. What are the harms of menopausal hormone therapy when used to prevent chronic conditions? 3. Do benefits and harms differ by subgroups? Subgroups include women with premature menopause; surgical menopause; age of use; types, doses, and modes of delivery of hormones; and presence of comorbidities.