Testosterone and the Metabolic Syndrome

Testosterone and the metabolic syndrome

Stefan Arver, MD, PhD, Reproductive Medicine Center, Karolinska Institute, Stockholm, Sweden

In the USA 23% of men have the metabolic syndrome in which insulin resistance plays a key role. Epidemiologic studies indicate that insulin levels and testosterone (T) are inversely correlated. Aims: 1) To define the dose response relationship between insulin sensitivity and T in men. 2) To elucidate the mechanism of the relative hypogonadism in men with insulin resistance. Methods: 59 men (44 to 65 yr) were studied: 26 had normal glucose tolerance (NGT), 12 had impaired glucose tolerance (IGT), 21 had diabetes (DM). All had a euglycemic hyperinsulinemic clamp; 15 had testing with GnRH and hCG after endogenous LH and T were suppressed with a GnRH antagonist. Results: T levels were lower in men with DM (390 ± 40 ng/dL) and IGT (380 ± 42 ng/dL) than those with NGT (518 ± 36 ng/dL), p<0.05 despite similar BMI. There was an inverse relationship between T and BMI (r=-0.44, p<0.05) and WHR (r=-0.35, p=0.008). Insulin sensitivity (M) correlated with T (r=0.35, p=0.007) particularly in men with IGT. Men with hypogonadal T levels (n=10) were more insulin resistant than those with normal T (n=49), M = 3.8 ± 2.2 vs. 6.1± 3.5. mg/kg/min, p<0.05. No correlation was seen between M and LH secretion. A strong correlation was observed between M and the T response to hCG (r=0.7, p<0.005). Conclusions: Testosterone is an important modulator of insulin sensitivity in men. The relative hypogonadism in men with insulin resistance is due to impaired Leydig cell secretion of T.