Testosterone and Coronary Artery Disease

Abstract

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.

An old emperor finds new clothing: rejuvenation in our time

“…This regular association in observational studies has become overinterpreted as a risk factor (rather than a consequence), leading to prediction of beneficial (rather than adverse) effects of testosterone treatment. [42][43][44][45] This complacency led to a misplaced focus on prostate cancer as the major risk of testosterone treatment in older men. 35,36 This paper saliently highlights the important principle that relatively small adverse effects involving the most common cause of death-cardiovascular disease-overwhelms even substantial benefits on less common or non-fatal disorders.…”

Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement

“…Testosterone induces vasodilatation; decreases total cholesterol, low-density lipoprotein, and triglycerides levels; and inhibits fatty streak formation, indicating that androgens may have protective effects against atherosclerosis (45,46,55). On the other hand, supraphysiological doses of testosterone reduce high-density lipoprotein and promote unfavorable changes in the lipid profile (26).…”

Androgen stimulates endothelial cell proliferation via an androgen receptor/VEGF/cyclin A-mediated mechanism

“…THE ROLE OF ANDROGENS in cardiovascular functions is controversial, and both beneficial and detrimental effects of androgens have been reported (25,33,55). Epidemiological studies suggest that males are at a greater risk for cardiovascular disease compared with age-matched females during their reproductive years (25,33,55).…”

“…Epidemiological studies suggest that males are at a greater risk for cardiovascular disease compared with age-matched females during their reproductive years (25,33,55). This sex difference has been postulated to be attributable to the estrogen-protective and/or androgen-detrimental effects on the cardiovascular system.…”