Background  Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients.
Methods  In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients′ HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT.
Results  The average levels of total testosterone (TT) in HH and healthy group were (0.9±0.6) nmol/L and (18.8±3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14±5.16 vs 2.00±1.38, P <0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6±414.7 vs 414.2±267.5, P <0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1±0.6) mmol/L vs (4.7±0.3) mmol/l, P <0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14±5.16 to 2.97±2.16, P <0.01), insulin AUC (from 698.6±414.7 to 511.7± 253.9, P <0.01) and hsCRP (from (1.49±1.18) mg/L to (0.70±0.56) mg/L, P <0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT.
Conclusions  HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients′ insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases (CVD) in future.