Hormone replacement therapy and cardiovascular prevention. Where are we now?

During their fertile period women suffer significantly less atherosclerotic cardiovascular disease (particularly myocardial infarction) than men. This benefit progressively disappears after menopause, to equalize after the sixth decade of life. Experimental studies in animal and human models demonstrated the existence of physiological mechanisms suggesting that estrogens could be responsible for this cardiovascular protection, and retrospective analysis of clinical studies showed that post menopausal women who had used hormonal replacement therapy (HRT) suffered less cardiovascular events. These observations stimulated the execution of several prospective, randomized clinical trials (some of them with a large number of patients and prolonged follow-up) in post menopausal women, with the aim of proving the hypothesis that HRT could prevent major cardiovascular events. Such hypothesis could not be demonstrated in any of those studies because HRT was not beneficial, and in several cases it was even deleterious in some aspects. Criticism has arisen over some of the methodological aspects of those prospective trials, basically regarding the age of the included patients and the timing of the beginning of HRT. There are also biological reasons that can explain the contradiction. A new hypothesis, also based on experimental and clinical observations, suggests the possibility that beginning HRT in younger women and earlier after menopause could yield different results.