Gender considerations in hypertension pathophysiology and treatment

Cardiovascular disease is the leading cause of death among women, yet clinical trials have not evaluated specific treatment strategies for women. Recently, there has been an expansion of scientific literature exploring differences between women and men with hypertension and cardiovascular disease. The cardioprotective effects of estrogen have been well demonstrated, and the loss of endogenous estrogens with aging contributes to the rapid increase in the incidence of coronary artery disease after menopause. Many of the adverse effects of estrogen deficiency are reversible with estrogen replacement. Estrogen improves lipoprotein profiles, has vasodilatory effects on the endothelium, and inhibits vascular smooth muscle cell growth and constriction. These effects likely all contribute to the reduction in coronary artery disease in the presence of estrogen, and the clinical benefits are not attenuated by concurrent progestins. There are gender-specific differences in the epidemiology of hypertension and coronary artery disease, as well as differences in the pathophysiology and clinical manifestations of disease. Given important experimental interactions between estrogens and the major classes of antihypertensive agents, as well as secondary benefits such as a possible reduction in bone loss with certain agents, a gender-specific approach to hypertension appears to be warranted. Future clinical trials will need to address gender-specific differences in treatment approaches.