Testosterone modulates cardiac contraction and calcium homeostasis: cellular and molecular mechanisms

The incidence of cardiovascular disease rises dramatically with age in both men and women. Because a woman's risk of cardiovascular disease rises markedly after the onset of menopause, there has been growing interest in the effect of estrogen on the heart and its role in the pathophysiology of these diseases. Much less attention has been paid to the impact of testosterone on the heart, even though the levels of testosterone also decline with age and low-testosterone levels are linked to the development of cardiovascular diseases. The knowledge that receptors for all major sex steroid hormones, including testosterone, are present on individual cardiomyocytes suggests that these hormones may influence the heart at the cellular level. Indeed, it is well established that there are male-female differences in intracellular Ca2+ release and contraction in isolated ventricular myocytes. Growing evidence suggests that these differences arise from effects of sex steroid hormones on processes involved in intracellular Ca2+ homeostasis. This review considers how myocardial contractile function is modified by testosterone, with a focus on the impact of testosterone on processes that regulate Ca2+ handling at the level of the ventricular myocyte. The idea that testosterone regulates Ca2+ handling in the heart is important, as Ca2+ dysregulation plays a key role in the pathogenesis of a variety of different cardiovascular diseases. A better understanding of sex hormone regulation of myocardial Ca2+ homeostasis may reveal new targets for the treatment of cardiovascular diseases in all older adults.