The lost promise of hormone replacement therapy and heart disease.

Since the first secondary prevention trials were published in 1998, the prospect of hormone replacement therapy to prevent atherosclerotic heart disease in postmenopausal women has changed dramatically. Early harmful effects of hormone replacement therapy and lack of beneficial effects on coronary heart disease event rates in high-risk women have challenged the beneficial results gleaned from observational studies in the past. In this article, the effects of estrogens on lipids, hemostatic parameters, inflammation, and the vascular wall are described. The discrepancies that have arisen between the previous observational studies and recent randomized clinical trials are discussed: The current available data indicate that estrogens are beneficial to healthy endothelium but are harmful once atherosclerotic disease has developed.