Circumstances of life and food supply have changed in developed countries, resulting in an increasing prevalence of overweight. As a consequence, a complex disorder consisting of visceral obesity, dyslipidemia, insulin resistance and hypertension emerges: the so-called metabolic syndrome leads to the manifestation of diabetes type 2 and cardiovascular disease.
In men, testosterone deficiency contributes to the generation of the metabolic syndrome, as demonstrated by epidemiological and interventional approaches. Correspondingly, testosterone substitution in hypogonadal men is able to invalidate the mechanisms of the metabolic syndrome by various pathways. It has reciprocal effects on the generation of muscle and visceral fat tissue by exerting influence on the commitment of pluripotent stem cells. In addition, testosterone inhibits further development of pre-adipocytes. It also enhances insulin sensitivity of muscle cells by augmenting mitochondrial capacity and fostering expression of oxidative phosphorylation genes. These effects are exerted via androgen receptor-mediated mechanisms. Epidemiological and first interventional approaches indicate that testosterone substitution is especially helpful in preventing or attenuating disturbances of glucose metabolism and the metabolic syndrome in aging men with late-onset hypogonadism and in Klinefelter patients. However, large-scale double-blind placebo-controlled interventional studies of testosterone substitution therapy are required to corroborate these findings.