ABSTRACT
Introduction The evidence that oestrogen alone (oestrogen replacement therapy, ERT) or in combination with a progestin (hormone replacement therapy, HRT) may be beneficial in preventing cardiovascular disease (CVD) in post-menopausal women came from numerous large epidemiological observational studies over the past several decades. These strongly suggested that oestrogen has a cardioprotective effect. In addition, a lower incidence of coronary heart disease (CHD) in pre-menopausal women is believed to be due to a higher oestrogen level, and thus more ‘cardioprotected’, naturally. In contrast, post-menopausal women are particularly vulnerable to postmyocardial infarction (post-MI) morbidity and mortality in view of their age and generally widespread coronary artery disease (CAD) at the time of presentation. Improving the outcome as well as lowering the incidence of CHD by replacing oestrogen thus seems an attractive therapeutic approach. However, more robust evidence from several recent large prospective randomized placebo-controlled trials repeatedly provided disappointing results that HRT is neither beneficial in primary prevention nor secondary prevention of major cardiovascular events in this population. The data from these randomized trials contrasted sharply from those of promising prospective cohort studies and many mechanistic studies that have shown potential vascular benefits. Few arguments had been raised to try to explain the discrepancy. One of these arguments was the bias in patient selection theory that women on HRT might have been healthier and taken a greater interest in modifying cardiovascular risks-the ‘healthy woman’ hypothesis. Uncertainty also exists about the duration and optimal type of HRT regimen to use, because different oestrogens and progestins may have yielded different results.
