Testosterone and the cardiovascular system

Low testosterone is associated with an increased risk for coronary artery disease through the promotion of a pro-atherosclerotic environment.[5][8][9] Some research has identified testosterone as a vasodilator and an endothelium-repairing hormone within many regions in the body, including the coronary arteries.[10][11] Recent research depicts testosterone as important in decreasing the production of inflammatory cytokines such as tumor necrosis factor alpha, interleukin-1beta and interleukin-6, which are influential in atherosclerotic profiles.[10][12] Although it is believed that the reduction in inflammatory cytokines is related to a decreased atherosclerotic profile, the full explanation of this mechanism requires further research.[12][13]

Testosterone has also shown to be effective as an anti-atherosclerotic through preventing aortic cholesterol deposition in both rabbits fed high cholesterol diets and mice with low-density lipoprotein gene knockout.[10][14] Fatty deposition within the aorta associated with low endogenous testosterone has been determined to be independent of the androgen receptor.[10] Although the mechanism has yet to be fully determined, aromatase activity and the activation of estrogen receptor alpha is partially responsible for the atherosclerotic profile characteristic of low testosterone.[10]

Decreased systemic testosterone in men has also been reported in men with heart failure, whereby the severity of the disease is proportional to the reduction in systemic testosterone levels.[5] Although a direct mechanism of action is not fully understood, some research attribute low testosterone to advancing side effects of heart failure, such as decreased exercise ability, decreased muscle mass, fatigue/dyspnea and cachexia.[5]

Physiological testosterone is crucial for normal functionality in men. Long-term administration of physiological testosterone in mouse models has shown to be atheroprotective by increasing the HDL portion of cholesterol (the anti-atherosclerotic cholesterol).[10][15] The beneficial action of testosterone in elevating the HDL fraction can be attributed to its conversion via aromatase activity in adipose tissue into 17-beta estradiol and its subsequent activation of estrogen alpha-receptors; thus, more testosterone leads to greater conversion into estrogen and thus a healthier lipid profile.[10] This understanding has been determined in several studies, although results of these studies are contradictory.[10][16][17]

Testosterone replacement therapy in men diagnosed with pre-existing heart disease has been related to an increased risk of myocardial infarction.[18] Furthermore, recent research has linked testosterone replacement therapy to an increase in deaths and other cardiovascular occurrences in men whom document a history of coronary artery disease.[19] Further research is required to determine the full extent to which testosterone replacement therapy in aging men plays a role in the risk and/or advantage of cardiovascular occurrences.[20]