[Effects of hormone replacement therapy in menopause on cardiovascular risk. Need for a European study]

The increased risk of coronary heart disease (CHD) after menopause is currently attributed to estrogen deficiency. Many epidemiological (case-control and prospective) studies have reported a decreased risk (0.5-0.7) of CHD in postmenopausal women receiving hormone replacement therapy (HRT). However, there are some discordant studies, among which the Framingham study. Moreover, the observational studies were subject to several biases that may have falsely elevated the apparent benefit of estrogen: women taking estrogen tend to be wealthier, more educated and healthier than untreated women. Large randomized clinical trials of secondary (HERS, WEST) or primary (WHI) prevention have not confirmed cardioprotection with HRT. However, these studies used orally administered estrogens, while the non-oral route of administration is frequently used in Europe. From a biological point of view, estrogen has multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, concerning hemostasis factors, a pro-coagulant effect can be induced by the first pass liver effect of estrogen when administered orally, which is not observed with the non oral routes of administration. In addition, the synthetic progestin medroxy-progesterone acetate (MPA) inhibits the beneficial effects of estrogen on the arterial wall, whereas natural progesterone does not. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non-oral estrogens (administered percutaneously or transdermally) associated with natural progesterone.