Sex differences in the vascular function and related mechanisms: role of 17β-estradiol

The incidence of cardiovascular disease (CVD) is lower in premenopausal women but increases with age and menopause compared with similarly aged men. Based on the prevalence of CVD in postmenopausal women, sex hormone-dependent mechanisms have been postulated to be the primary factors responsible for the protection from CVD in premenopausal women. Recent Women's Health Initiative studies, Cochrane Review studies, the Early Versus Late Intervention Trial with Estradiol Study, and the Kronos Early Estrogen Prevention Study have suggested that beneficial effects of hormone replacement therapy (HRT) are seen in women of <60 yr of age and if initiated within <10 yr of menopause. In contrast, the beneficial effects of HRT are not seen in women of >60 yr of age and if commenced after 10 yr of menopause. The higher incidence of CVD and the failure of HRT in postmenopausal aged women could be partly associated with fundamental differences in the vascular structure and function between men and women and in between pre- and postmenopausal women, respectively. In this regard, previous studies from human and animal studies have identified several sex differences in vascular function and associated mechanisms. The female sex hormone 17β-estradiol regulates the majority of these mechanisms. In this review, we summarize the sex differences in vascular structure, myogenic properties, endothelium-dependent and -independent mechanisms, and the role of 17β-estradiol in the regulation of vascular function.