The significant relationship between hormone substitution therapy during menopause and reduced cardiovascular risk has been demonstrated in many studies. The beneficial effect of natural estrogens on plasma lipids has been questioned, accounting for no more than 25% of the vascular effect. Natural estrogens act on the vascular wall by favoring the penetration of potassium into the cell and stimulating synthesis of prostacycline synthetase and prostaglandin cyclooxygenase. Capacity for dilatation is partially restored and sensitivity to vasoconstrictor substances is reduced by increased synthesis of endothelium derived relaxing factor (EDRF). In addition to the endothelium-dependent mechanism, there is also an endothelium-independent mechanism due to the anti-calcium effect and endothelin antagonism. Thus natural estrogens increase vascular flow and reduce resistance. Besides the direct or indirect vascular effect, estrogens also have an anti-atherogenic effect resulting from a modulation of gene expression due to specific receptors situated on smooth muscle and endothelial cells. Indications for hormone substitution have been modified due to this better understanding of the different actions of natural estrogens. Patients with atheromatosis or hypertension are legitimate candidates.
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