Oestrogens and the heart

The incidence of cardiovascular disease is lower in women before the menopause compared with men, while menopausal women have an incidence of coronary disease similar to that of men of the same age. This is mainly dependent upon oestrogen deficiency. Large-scale epidemiological studies have demonstrated that oestrogen replacement therapy leads to approximately 50 per cent reduction of cardiovascular disease in women taking hormones, compared with untreated women. Multiple mechanisms have been proposed to explain the cardiovascular risk reduction observed in women on oestrogen therapy. Oestrogens positively affect plasma lipids and exert a beneficial effect upon carbohydrate metabolism and the haemocoagulation profile. Oestrogens may also have anti-atherogenic properties. Recent in vitro studies have demonstrated that oestrogens may positively influence all the steps involved in the formation of the atherosclerotic plaque (accumulation of cholesterol in the arterial wall, arterial smooth muscle cell proliferation, platelet aggregation, collagen and elastin production). Angiographic studies conducted in humans have demonstrated that women on oestrogens have significantly less coronary disease and less severe occlusion scores compared with women not taking hormone replacement therapy. Animal and human studies have shown that oestrogens act as vasodilating substances. Endothelium-dependent mechanisms have been identified and imply that oestrogens act through the endothelial release, mainly, of nitric oxide, a potent vasodilating substance which has been identified with EDRF (endothelium derived relaxing factor). More recently, oestrogens have been shown to affect also the vascular tone in the absence of the endothelium. Therefore, endothelium-independent mechanisms could be involved in the pathogenesis of the oestrogens' vascular effects. There is evidence that oestrogens have calcium antagonistic properties; this mechanism may be responsible for the reduction of peripheral vascular resistance observed in women on hormone replacement therapy and may slow the progression of coronary artery disease. The menopausal age is characterized by an imbalance of the neurohormonal system. Sudden increases of plasma catecholamines are evident when women have hot flushes, a typical clinical sign of the menopausal period. The abnormal release of catecholamines may reduce coronary flow reserve and increase peripheral vascular resistance and, therefore, may be dangerous for the heart. It has been shown, by means of the study of heart rate variability, that oestrogens are effective in modulating the neurohormonal system. The reduction of sympathetic tone has beneficial effects on coronary flow reserve and may be important in explaining the cardioprotective effect of oestrogens. Peripheral and coronary vasodilation observed in women on hormone replacement therapy might be also due to the inhibition of the release of vasoconstrictor factors such as endothelin-1 by oestrogens. Therefore, oestrogens protect the heart against coronary artery disease and they are now regarded as being as important as aspirin and antihypertensive drugs were in the past. Hormone replacement therapy should be considered in every menopausal woman to possibly prevent the occurrence of cardiovascular disease or, if already present, to slow its progression.