The heart as a target for oestrogens

Observational studies have consistently shown a markedly decreased risk of cardiovascular disease in postmenopausal women when treated with oestrogens. This review discusses plausible mechanisms for the physiological effects of oestrogens in healthy and diseased hearts. Oestrogens have well-documented effects on blood lipids and the regulators of the cardiovascular system, which should reduce risk. In addition, the heart is a primary target for oestrogens with functional oestrogen receptors in the coronary vasculature and on cardiac myocytes and fibroblasts. Rapid oestrogen effects include vasodilatation and anti-arrhythmic effects by actions on ion channels, and some of these effects may be pharmacological rather than physiological. Longer term responses to physiological levels of oestrogen include an increased expression of nitric oxide synthase in myocytes and endothelial cells as well as proinflammatory and pro-arrhythmic effects. Oestrogens induce growth of non-proliferating fibroblasts but inhibit the replication of proliferating fibroblasts. In contrast to the observational studies, two randomised, controlled studies of oestrogen and progestins in postmenopausal women with coronary heart disease have now shown increased coronary events, especially in the first year of study, and no change in the progression of coronary atherosclerosis. Further studies of the complex effects of oestrogens on healthy and diseased animal models are essential. Large clinical trials of the newer selective oestrogen receptor modulators to lower cardiovascular risk in both males and females should be considered as a priority.