Testosterone and coronary artery disease

The strongest independent risk factors for coronary artery disease (CAD) are increasing age and male gender. Whilst a wide variation in CAD mortality exists between countries, a male to female ratio of approximately 2:1 is consistently observed. These observations have led to the assumption that testosterone may exert a detrimental influence on the cardiovascular system. Despite this, coronary atherosclerosis increases with age, whilst a marked fall in serum bioavailable testosterone levels is observed. Similarly, low testosterone levels are also associated with other cardiovascular risk factors and increased expression of mediators of the atherosclerotic process. This in itself suggests that testosterone does not promote atheroma formation. Moreover, epidemiological studies show an inverse relationship between testosterone levels and surrogate markers of atherosclerosis, which suggests that it may be a testosterone deficient state, rather than male sex which is associated with CAD. In cholesterol-fed animal models, atherosclerosis is accelerated by castration and reduced after testosterone replacement therapy. Testosterone has also been shown to improve myocardial ischemia in men with angina pectoris. Consequently, increasing evidence suggests that the process of atherosclerosis is beneficially modulated by testosterone. These studies are the focus of this chapter.