Functional hypogonadism: Diabetes mellitus, obesity, metabolic syndrome, and testosterone

Abstract

Low levels of blood testosterone are more frequently found in patients with type 2 diabetes mellitus, obesity, and metabolic syndrome than in the general population, as shown in epidemiological studies. All these conditions are associated with insulin resistance, and there is a two-way relationship between them and low testosterone levels: not only can the metabolic disorder lead to hypogonadism, but testosterone deficiency can also contribute to type 2 diabetes mellitus, obesity, and metabolic syndrome. In addition to the sexual symptoms of loss of libido, erectile dysfunction (ED), and absence of morning erections, low testosterone levels are associated with an increase of adipose tissue and decrease of muscle mass, not only because testosterone induces differentiation of mesenchymal pluripotent cells into myocytes and inhibits conversion into adipocytes. Low testosterone levels also favor incorporation of triglycerides in fat cells due to inhibition of lipoprotein lipase activity. Most deaths from type 2 diabetes, obesity, and metabolic syndrome are due to cardiovascular diseases, and there is an increase of these disorders in men with low testosterone levels. There is consistent scientific evidence that testosterone replacement in hypogonadal patients can ameliorate the risk factors for cardiovascular diseases and decrease mortality. On the other hand, functional hypogonadism can be reversed by weight loss and better control of diabetes. The few studies linking testosterone replacement to increase of cardiovascular death present serious methodological issues and are not confirmed by a careful meta-analysis.