Body fat content and testosterone pharmacokinetics determine gonadotropin suppression after intramuscular injections of testosterone preparations in normal men.

Interindividual differences in gonadotropin suppression achieved by short- and long-acting intramuscular testosterone (T) preparations were studied to detect factors hindering complete suppression of gonadotropins as the prerequisites for effective male contraception. Forty healthy men received a single injection of T propionate; 4 weeks later they received 2 injections of 1000 mg of T undecanoate (TU) given 6 weeks apart. Following TU, declines of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were consistent in 17.5% and almost absent in 25% of men. Men showing the most rapid and consistent declines in LH and FSH levels received a slightly higher dose per body weight of TU (13.1 +/- 0.6 vs 11.3 +/- 0.6 mg/kg; P = NS) and reached higher maximal concentrations of total T (40 +/- 4.8 vs 18.4 +/- 2.4 nmol/L; P < .001) and free T as well as estradiol. Men with high fat mass (mean +/- SEM, 10.3 +/- 1.5 vs 23.2 +/- 6.4 kg) had a delayed increase in T levels and an impaired relative decline in LH (12 +/- 2% vs 53 +/- 10%) and FSH (17 +/- 6%. vs 70 +/- 25%) levels within the first 2 weeks after the first TU injection. We conclude that overweight reduces the chance of rapid and profound gonadotropin suppression during treatment with TU. Body weight needs to be considered to avoid failure of hormonal male contraception.