ABSTRACT
Sex differences in the development of hypertension and cardiovascular disease (CVD) have been well described in humans and in animal models. In general, men are at greater risk for CVD and hypertension than premenopausal women of the same age.1,2 Ambulatory blood pressure measurements have consistently found that men have higher blood pressures than premenopausal, age-matched women.3-5 After menopause the sex difference in the incidence of hypertension is lost.6 In animal models of hypertension, studies have also shown males to have higher blood pressure than females. For example, in Dahl-salt hypertensive, spontaneously hypertensive rats (SHR), and reduced renal mass, high salt-fed rats, males have higher blood pressures than the females.7-12
While the mechanisms underlying sex differences are poorly understood, there is significant evidence for a role for both testosterone in the development of13,14 and estrogen in the protection against15-18 high blood pressure. Evidence supporting the hypothesis of estrogen involvement in the differential expression of CVD and hypertension between men and women has been shown by several laboratories.1,17,19 While estrogen replacement therapy has been shown to reduce low-density lipoprotein cholesterol and increase high-density lipoproteins levels20,21 these protective findings contrast with the findings of the Women’s Health Initiative (WHI)22,23 and Heart and Estrogen/progestin Replacement Study (HERS) I and II.24,25 These trials failed to find a protective effect for horomone replacement therapy (HRT) against CVD. It has been suggested that the type of estrogen used in the replacement trials, and the fact that many of the women had already gone through menopause may account for these outcome discrepancies. It has been suggested that initiation of HRT in
the perimenopausal period during rather than after menopause may have provided CVD protection.26
