Clinical cardiovascular studies of hormone replacement therapy.

Coronary artery disease (CAD) is the number 1 cause of death and disability in the Western world. The incidence of CAD increases with age, although, on average, women present with symptomatic CAD about 10 years later than men. The belief that hormone replacement therapy (HRT) may reduce the incidence of CAD is based on its favorable effects on (1) vasoreactivity, (2) progression of atherosclerosis, (3) lipids and lipoproteins, (4) hemostasis, and (5) impaired glucose tolerance. However, unopposed estrogen may be related to an increased risk of endometrial cancer. The belief that HRT has an overall beneficial effect on cardiovascular disease comes from the results of prospective cohort studies. The Heart and Estrogen/progestin Replacement Study (HERS), however, showed no beneficial effect of HRT on cardiovascular morbidity and mortality. Uncertainty exists about the duration and optimal type of HRT regimen to use, because different estrogens and progestins have yielded different results. Results of ongoing trials addressing similar questions will be published in future years. The Women's Hormone Intervention Secondary Prevention (WHISP) pilot study, using a different HRT regimen from that used in HERS, will assess the effect of HRT on lipid and hemostatic risk markers of heart disease, and it may provide the rationale for a large trial evaluating the effect of HRT on morbidity and mortality.