Sex Hormones and Vascular Function

The relationship between sex hormones and cardiovascular function and disease has long been recognized. As early as the 1950s, researchers concluded that although levels of cholesterol played a major role in the development of cardiovascular disease (CVD), other factors, including gender and hormones, played a role as well. (Anonymous, 1958). Since that time, despite extensive research focusing on the effects of estrogen on vascular function, the relationship remains poorly understood. Furthermore, clinical treatment of postmenopausal women with hormone replacement therapy (HRT) continues to be controversial due to conflicting findings in clinical trials. Until the 1990s, extensive observational data suggested that HRT was cardioprotective. However, results from the Heart and Estrogen/Progestin Replacement Study (HERS-I and – II) did not confirm a protective effect of HRT on the heart. (Hulley et al 1996; Grady et al 2002). Later, data from the Women’s Health Initiative (WHI) reported an increase in coronary heart disease (CHD) risk in women treated with combined estrogen-progestin compared to placebo, while the WHI unopposed-estrogen arm showed no increase in CHD events (Roussow et al, 2002; Anderson et al, 2004). Since release of the WHI, follow-up analyses have shown that the timing of initiation of HRT makes a difference in outcomes. These analyses showed that younger postmenopausal women who initiate therapy at the time of menopause are not at increased risk of CHD events compared to women who initiate therapy at a later age. In this chapter, we will discuss the pathophysiologic effects of sex hormones on the vasculature, describe both clinical and basic research that has led us to our current understanding, and conclude with future perspectives on avenues of investigation that may lead to innovative treatments for postmenopausal women.