Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism

Background: Excessive testosterone in males or estrogens in females could explain their differences in coronary heart disease event rates. As a contraceptive testosterone is likely to be used at large scale the role of testosterone in increasing the risks of coronary heart disease needs investigation. Aim: To look at the role of testosterone in development of insulin resistance and other cardiovascular risk factors. Design: Prospective, before-after study on ten male subjects with idiopathic hypogonadotrophic hypogonadism pre- and post-testosterone replacement therapy; outcome measure; anthropometry, lipoprotein profile and M value (whole body glucose disposal rates on standard hyperinsulinemic euglycemic clamp; at insulin infusion rate: 40 mU · m^-2). Results: Pre-treatment serum testosterone was 0.43 (0.515) ng · ml^-1 LH was 1.29 (0.08) IU · L^{- 1}, and FSH was 1.54 (0.08) IU · L^-1. None had glucose intolerance. After replacement testosterone levels increased to 9.4 ng · mL^-1 (p = 0.005); weight increase of 5.0 kg (p=0.140), body mass index increase of 1.2 kg · m^-2 (p=0.28) and the change in waist to hip ratio (p=0.31) were not statistically significant. M-value (mg. kg · min^-1) did not change after testosterone therapy (5.86 [0.72] vs 5.29 [0.82], p=0.62). Insulin levels (mU · L^-1) achieved during the clamps were 89.5 (14.2) before and 146 (32.2) after androgen therapy (p=0.127). There was no change in glucose area under curve (mg · min · dL^-1) (14406 [502.2] vs 12557 [826.5], p=0.312). On testosterone replacement therapy total and LDL cholesterol levels (mg · dL^{- 1}) declined (122.5 [13.4] vs 91.6 [5.0], p=0.04; 65.9 [9.9] vs 39.4 [7.3], p=0.05); Ratio of total cholesterol to HDL ratio also decreased significantly (p=0.05). Changes of serum triglycerides (p=0.25) and HDL cholesterol (p=0.19) did not attain statistical significance. Conclusions: Insulin sensitivity does not decrease on testosterone replacement therapy of male subjects with idiopathic hypogonadotrophic hypogonadism. Testosterone replacement was associated with decrease in other cardiovascular risk factors.