Sex hormones and the cardiovascular system: Effects on arterial function in women

1. It has long been hypothesized that oestrogen may be cardioprotective. This hypothesis is supported by diverse and comprehensive mechanistic studies in animals and humans. Consistently, in observational studies, oestrogen use in post-menopausal women significantly reduced cardiovascular disease. Contrastingly, large interventional trials focusing on chronic disease prevention in older post-menopausal women have suggested neutral (oestrogen alone) or adverse (combined oestrogen/progestin preparations) cardiovascular effects. 2. The negative initial interpretation and extrapolation of the early randomized, controlled interventional trials, primarily the Women's Health Initiative, has recently been theoretically reconciled with the positive mechanistic and observational studies. As a new interventional literature emerges, it has been suggested that if oestrogen is used from menopause onwards it is likely to be protective, but if instituted after endothelial damage has occurred in an oestrogen-deficient post-menopausal state, the beneficial vessel wall effects are not observed and the procoagulant effects result in overall increased cardiovascular risk. 3. The present article reviews the literature on arterial function and oestrogen use in the setting of the early endothelial protection theory. This theory is generally supported by the data on oestrogen effects on arterial function. In general, in studies of premenopausal women the effects of oestrogen were positive, with similar benefits noted if oestrogen was used early after menopause. However, where hormone therapy was commenced some years after menopause, the beneficial effects on arterial function were not observed. In clinical practice, hormone therapy is primarily used at menopause for the treatment of menopausal symptoms. The data on arterial function reviewed herein, along with emerging interventional human studies, suggest that the cardiovascular effects of this practice are not adverse.