The putative mechanisms underlying testosterone and cardiovascular risk

Abstract

The use of testosterone supplementation therapy (TST) is increasing primarily in men with symptomatic hypogonadism. While TST has been shown to have numerous benefits, as its use increases, the role on cardiovascular health must be explored. Previous evidence showed no adverse cardiovascular risks associated with TST use; however, more recent studies suggest that there may be an associated risk. The exact mechanism by which TST may contribute to cardiovascular risk has not been elucidated. Numerous mechanisms have been proposed which include testosterone’s effect on thromboxane A2 receptors, vascular adhesion molecule 1 receptors, erythropoiesis, and obstructive sleep apnea, all of which can ultimately lead to atherogenesis and increased cardiovascular risk.

Low Plasma Testosterone is Associated with Elevated Cardiovascular Disease Biomarkers

“…42 Our study of more than 10,000 men supports previous findings that hypogonadal men are at risk for developing CV disease; moreover, this panel of biomarkers implies that hypogonadal men are specifically at risk for ischemia, heart failure, atherosclerosis, inflammation, and dyslipidemia. 43 …”

135 Low Plasma Testosterone is Associated with Elevated Cardiovascular Disease Biomarkers

“…42 Our study of more than 10,000 men supports previous findings that hypogonadal men are at risk for developing CV disease; moreover, this panel of biomarkers implies that hypogonadal men are specifically at risk for ischemia, heart failure, atherosclerosis, inflammation, and dyslipidemia. 43 The molecular mechanisms linking T and CV risk have yet to be precisely defined. Several studies suggest that androgens directly inhibit the development of atherosclerotic plaques through reducing lipid lesions, preventing foam cell formation, preventing endothelial injury, modulating the coagulation pathway, and inhibiting inflammation.…”

Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk

“…The function of human TXA 2 is to assist in platelet aggregation and vascular smooth muscle contraction, 109,110 and increased platelet aggregation potentially promotes atherogenesis/thrombosis. 111 During numerous thrombotic CV events, including unstable angina, the synthesis of TXA 2 is increased. 112 However, there is no direct evidence for an association between TXA 2 receptor density and CV risk in humans, 111,113 nor is there evidence that a T-induced TXA 2 increase induces increased CV risk.…”

“…111 During numerous thrombotic CV events, including unstable angina, the synthesis of TXA 2 is increased. 112 However, there is no direct evidence for an association between TXA 2 receptor density and CV risk in humans, 111,113 nor is there evidence that a T-induced TXA 2 increase induces increased CV risk.…”