Pharmacology of oestrogens and progestogens and cardiovascular risk

The rationale for oestrogen replacement therapy relies mainly on two types of evidence, both of which are flawed: (1) the relative protection of women in premenopausal status against cardiovascular diseases and the increase o f risk following menopause; (2) data from observational studies that showed a lower prevalence of cardiovascular events in women taking hormone replac ement therapy (HRT) compared with those not taking such treatment (OR=0.65; 95 per cent CI: 0.59-0.71). Behind the former evidence there is the assump tion that the difference in risk before and after menopause is mostly due t o the lack of ovarian oestrogens in post-menopausal women. This is indeed a strong assumption since there are many other changes during and after meno pause. The second type of evidence assumes that the ORs given by the observ ational studies are unbiased. In fact, there are reliable data suggesting t hat women taking and not taking HRT are different in many respects, especia lly in their concerns for their health. This dimension has been proposed as an explanation for the correlation between compliance with placebo and sur vival. The only reliable approach is to perform adequately sized and long-t erm follow-up randomized trials. Although they should not be viewed as conc lusive, the results of the first completed trial do not support the hypothe sis that HRT is beneficial in women with a history of coronary disease.