Coronary heart disease and menopause management: the swinging pendulum of HRT.

The Women's Health Initiative comprised a randomized placebo-controlled clinical trial of therapeutic and dietary interventions influencing postmenopausal women's health. One arm evaluated hormone replacement therapy and its effects on major health outcomes. Initial publication of the preliminary results suggested overall harm from hormone replacement therapy, leading to a dramatic worldwide decrease in its use, and concerns from clinicians and regulatory authorities. Subsequent publications with more detailed analyses appear to have countermanded these initial concerns. Analyses of the studies have not been adherent to those specified in the original published protocol. Nominal confidence intervals should have been used only for the primary outcome, which was coronary heart disease. Initially reported as showing a significant increase in events with hormone replacement therapy, in a subsequent analysis of the full data the increase was no longer significant. Adjusted confidence intervals showed no significant increase for breast cancer, the primary adverse outcome. A major difference in the effects of hormones between younger and older women has emerged but this important finding has been minimized. For women under age 60 years or within 10 years of menopause, the final findings for all outcomes closely resemble those from observational cohorts. The raw data must be made available for independent assessment to obtain valid conclusions which may again change clinical practice.