Is hormone replacement therapy cardioprotective? Decision-making after the heart and estrogen/progestin replacement study.

Coronary artery disease (CAD) is the major cause of death in women. Postmenopausal status is associated with a twofold increase of risk for cardiovascular events, in part because of detrimental changes in plasma lipoproteins and endothelial function. Hormone replacement therapy (HRT) has beneficial effects on plasma lipids, flow-mediated vasodilation and fibrinolysis that could be expected to have positive effects on the incidence of cardiovascular events in many postmenopausal women. However, oral HRT also has procoagulant effects and clearly increases the risk of venous thromboembolism. The prothrombotic effects of oral estrogen are not a major concern for the majority of healthy women and major studies including the Framingham Heart Study and the Nurses' Health Study showed that HRT use is associated with protection from cardiovascular disease. In contrast, the Heart and Estrogen/progestin Replacement Study (HERS) failed to show a beneficial effect of oral HRT on cardiovascular events in older women with advanced CAD. In such women, the acute prothrombotic effects of oral estrogen may outweigh the long-term antiatherosclerotic effects of HRT. Until the results of other randomized controlled studies are complete, advice regarding HRT should be based on anticipated benefits on CAD risk factors versus the overall risk of both venous and arterial thrombosis.