For years researchers have postulated the cardio–protective effects of the endogenous estrogens, namely estradiol. Research published in 2012 in the journal Hypertension identifies a mechanism by which the estrogens regulate heart function. It appears that systemic estrogen receptors (ER alpha to be specific) and by association estradiol, the hormone that binds to the estrogen receptors, are necessary to regulate cardiac glucose metabolism. Glucose is critical for maintaining heart contractility and mass.
Using both ovariectomized (ovaries removed) and knockout mice (genes that regulate the receptors are knocked out or removed, producing animals without estrogen receptors), researchers found that cardiac glucose metabolism was significantly impaired. When a drug that increases estradiol actions was given to the ovariectomized animals, cardiac glucose function was restored.
Estrogen Receptors and the Heart Muscle
In another study researchers found that the number of estrogen receptors located on the heart nearly doubles during end-stage cardiac disease. Moreover, the patterns and locations of these estrogen receptors differ significantly between males and females. Since males die from heart failure more frequently and more rapidly than females, researchers speculate that the increase in cardiac estrogen receptors is a protective, compensatory reaction that slows down and maybe even prevents heart failure.
Estrogen Receptors, Glucose and the Healthy Heart
Under normal circumstances, healthy hearts derive most of their energy from free fatty acids with only a smaller percentage from glucose metabolism. During ischemic events or heart attacks, the metabolic balance switches and glucose metabolism increases significantly. Since estrogen receptors appear to mediate cardiac glucose metabolism, it is likely that circulating concentrations of estradiol, the hormone that binds to the estrogen receptor, also plays a role in heart health or, more specifically, in its ability to survive and recover post heart attack. The estrogen receptor-cardiac glucose connection may be the mechanism leading to the higher survival rates for women, especially women with higher circulating estradiol (pre-menopause).
Diabetes and Estradiol
Interestingly, in diabetic patients the metabolic pattern is reversed. Rather than an increase in glucose metabolism post heart attack, free fatty acid metabolism increases making it difficult for the heart to generate sufficient energy to recover. Researchers speculate that this may account for the increased rate of heart failure in individuals with diabetes. Indeed, in experimental (rodent) models of diabetes, research show that diabetics have lower estradiol levels. The research in humans is mixed.
These studies point to the importance of steroid hormones beyond their role in reproduction. The interplay between steroid hormones and cardiac function is but one example of many where the traditional view and nomenclature of reproductive, sex, or female hormones has become outdated and likely limits our understanding of health and disease.