Testosterone Making an Entry Into the Cardiometabolic World

Abstract

Testosterone, the predominant sex hormone in men, is produced by the testes under stimulation by the gonadotrophs in the pituitary, which in turn are controlled by gonadotropin-releasing hormone neurons in the hypothalamus. A young adult man generally produces 3 to 10 mg of testosterone daily, which translates into serum values of 300 to 1000 ng/dL. The consequences of classical male hypogonadism (primary or secondary) have been long known to physicians and patients alike and include decreased libido, erectile dysfunction, osteoporosis, reduced sexual hair, and changes in body habitus. Recently, we have come to appreciate that reductions in serum testosterone resulting from aging or chronic disease have signs and symptoms similar to those seen in classical male hypogonadism, along with increased fat mass, decreased lean body mass, decreased muscle strength, and diminished quality of life.1 During the past decade, reports have been trickling in, mainly from laboratory and epidemiological studies (and a few clinical studies), linking differences in serum testosterone levels to various cardiovascular risk factors and also directly to cardiovascular disease and death. The article by Khaw et al2 in this issue of Circulation is another link to this growing chain. Article p 2694 Thirteen years ago, Phillips et al3 reported that low total and free testosterone levels were inversely linked to coronary artery disease, even after adjusting for age and adiposity. This observation still holds true, as was recently supported by a study showing that men with angiographically proven coronary artery disease had lower levels of testosterone than those of controls.4 Furthermore, testosterone levels were negatively correlated to the degree of coronary involvement. A few population-based studies have been published that relate low serum testosterone level with risk of death. A study of male veterans showed that low testosterone was associated with increased risk of …