Obesity, type 2 diabetes, and testosterone in ageing men

In the absence of obesity, adverse lifestyle behaviours, and use of medication such as opioids serum testosterone concentrations decrease by only a minimal amount at least until very advanced age in most men. Obesity is heterogeneous in its phenotype, and it is the accumulation of excess adipose tissue viscerally associated with insulin resistance, dyslipidaemia, inflammation, hypothalamic leptin resistance and gliosis that underpins the functional hypogonadism of obesity. Both central (hypothalamic) and peripheral mechanisms are involved resulting in a low serum total testosterone concentration, while LH and FSH are typically in the normal range. Peripherally a decrease in serum sex hormone binding globulin (SHBG) concentration only partially explains the decrease in testosterone and there is increasing evidence for direct effects in the testis. Men with obesity associated functional hypogonadism and serum testosterone concentrations below 16 nmol/L are at increased risk of incident type 2 diabetes (T2D); high testosterone concentrations are protective. The magnitude of weight loss is linearly associated with an increase in serum testosterone concentration and with the likelihood of preventing T2D or reverting newly diagnosed disease; treatment with testosterone for 2 years increases the probability of a positive outcome from a lifestyle intervention alone by approximately 40%. Whether the additional favourable benefits of testosterone treatment on muscle mass and strength and bone density and quality in the long-term remains to be determined.