Testosterone and cardiovascular disease

Abstract

Low levels of endogenous circulating testosterone in men in community-based epidemiological studies are associated with an increased risk of mortality from all causes, with some studies identifying a link with cardiovascular (CV) disease. Testosterone deficiency is associated with several CV risk factors including central obesity, dyslipidemia, hypertension, and insulin resistance. Testosterone replacement therapy (TRT) in men with hypogonadism, when carefully replaced to the normal range, has been shown to improve some risk parameters including waist circumference, total and low-density lipoprotein cholesterol, lipoprotein(a), insulin resistance, and hyperglycemia. TRT does slightly lower high-density lipoprotein cholesterol in some trials; the clinical significance of this effect is not known. Beneficial effects of TRT have demonstrated reduced exercise-induced cardiac ischemia in men with chronic stable angina and improved functional exercise capacity, and Vo2max in men with moderate chronic cardiac failure. Evidence from well-conducted trials where TRT achieves normal testosterone values and meta-analysis of the studies have not identified any increased risk of major CV events. Some recent studies have shown increased CV risk, but have major flaws in design and either over- or under-treated patients. Clearly only a large, long-term, placebo-controlled randomized clinical trial may provide the definitive answer. The benefits of TRT on quality of life and sexual function are very important to the majority of men with hypogonadism. Furthermore, two retrospective studies have reported that TRT can reduce mortality in hypogonadal men with and without type 2 diabetes. Careful diagnosis, titration of testosterone dose to maintain levels within the mid-normal range, and long-term safety monitoring are key to the reduction in complications.