Hormone replacement therapy of the menopause, heart and blood vessels

The incidence of coronary heart disease (CHD) is lower in premenopausal wom en than in men and post-menopausal women of the same age. The higher CHD ra te after menopause is currently attributed to estrogen deficiency: many epi demiological (case-control and prospective) studies have reported a reduced risk (0.5-0.63) of CHD in post-menopausal women receiving hormone replacem ent therapy (HRT). Moreover, estrogens have multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, end othelial function, vascular reactivity and blood flow. However, the observa tional studies are subject to several biases that could falsely elevate the apparent benefit of estrogens: women taking estrogens tend to be wealthier , more educated and healthier than untreated women. The american HERS (Heart and Estrogen-progestin Replacement Study; 2.763 wo men) is a large multicenter randomized study of secondary prevention, desig ned to evaluate the efficacy of HRT. Results are disappointing, since no re duced risk was observed, and the risk of CHD was even higher in women recei ving HRT during the first year: 1.52 (CI 95% 1.01-2.29). In HERS study, the treatments consisted of conjugated equine estrogens and the synthetic prog estin medroxyprogesterone acetate (MPA) which are rarely used in Europe. In deed, the effects of HRT are not equivalent depending on the dose, the rout e of administration, the type of progestogen. It should be emphasized that MPA, contrarily to progesterone, inhibits the beneficial effect of estrogen s on lipids and experimental atherosclerosis. The route of administration o f estrogens is also involved : estrogens alter hemostasis factors, and when orally administered, they have a first pass liver effect, which favors hyp ercoagulability. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible benefical effect of non oral estrogens (g el or patch) associated with natural progesterone.