A comparative review of the risks and benefits of hormone replacement therapy regimens.

The Women's Health Initiative (a large, randomized, placebo-controlled trial) investigated the effect of conjugated equine estrogens combined with medroxyprogesterone acetate on specific potential long-term benefits and risks. A review of the clinical studies that have investigated different types and regimens of estrogens combined with progestins was conducted to assess how applicable the results of the Women's Health Initiative are to hormone replacement therapy regimens in general. The studies that were reviewed were limited to randomized clinical trials and observational studies that have been published over the last 15 years (1987-2002) and to meta-analyses and reviews that may have included the literature before 1987. The increased risks for venous thromboembolism, stroke, coronary heart disease, and breast cancer that were identified in the Women's Health Initiative trial have also been reported with postmenopausal hormone therapies that contain a variety of estrogen and progestin products. The beneficial effects that were noted in the Women's Health Initiative, with respect to reductions in fractures and colorectal cancer, have not been evaluated in large, randomized controlled trials that use different estrogen/progestin combinations; however, observational trials that used a variety of estrogen or hormone replacement therapy products and randomized clinical studies that evaluated bone mineral density (an excellent predictor of fracture risk) with different estrogen/hormone replacement therapy regimens would suggest that results would be similar to those found in the Women's Health Initiative. Although the relief of menopausal symptoms, the primary reason women seek treatment, was not included in the overall benefit/risk analysis of the Women's Health Initiative, numerous trials suggest that all therapies are effective. Overall, these data indicate that the benefit/risk analysis that was reported in the Women's Health Initiative can be generalized to all postmenopausal hormone replacement therapy products.