Hormone replacement therapy and cardioprotection: what is good and what is bad for the cardiovascular system?

The incidence of cardiovascular diseases (CVDs) increases after menopause and at any age postmenopausal women have a significantly higher incidence of CVD compared to premenopausal women. Several epidemiological findings suggest the causative pathogenetic role of ovarian hormone deficiency in the development of CVD in women. Ovarian hormones have several potential protective effects on the cardiovascular system and despite several observational studies have shown the beneficial effect of estrogens and estrogen/progestin associations on CVD, at the present, after the findings of randomized studies, the effect of hormone replacement therapy (HRT) in the prevention of CVD is still under debate. The randomized studies (Heart and Estrogen/Progestin Replacement Study [HERS] and Women's Health Initiative [WHI]) found largely concordant results with the observational studies except for the divergent findings about coronary heart disease (CHD). The discrepancy between the two arms of the WHI study suggests that two factors, time to initiation of HRT since menopause and estrogen/progestin associations, are of pivotal importance to explain the widely divergent findings on the cardiovascular effects of observational studies and randomized clinical studies. Basic science and animal studies together with clinical investigations and the results of clinical studies are concordant in suggesting that a long time since menopause is associated with a reduced protective effect of estrogens while the unfavorable effects upon coagulation remain unaltered. In early postmenopausal women, like the ones included in the observational studies, ovarian hormone replacement may be cardioprotective because of the responsiveness of the endothelium to estrogens that also buffer the detrimental effects upon coagulation. In late postmenopausal women ovarian hormones have either a null effect or even a detrimental effect because of the predominance of the procoagulant or plaque-destabilizing effects over the vasoprotective effects. Therefore, HRT has beneficial cardiovascular effects in younger women while it may have detrimental effect on coagulative balance and vascular inflammation and has little effect on cardiovascular functions in older women.