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 a short and a long-acting intramuscular testosterone (T) preparation were studied to detect factors hindering complete suppression of gonadotropins as the prerequisite for effective male contraception. 40 healthy men received a single injection of testosterone propionate (TP) and four weeks later, two injections of 1000 mg testosterone undecanoate (TU) given six weeks apart. Following TU, decline of LH and FSH was consistent in 17.5% and almost absent in 25% of men. Men showing the most rapid and consistent decline in LH and FSH received a slightly higher dose per bodyweight of TU (13.1 +/- 0.6 vs.11.3 +/- 0.6 mg/kg; n.s.) and reached higher maximal concentrations of total T (40 +/- 4.8 vs. 18.4 +/- 2.4 nmol/L; p<0.001) 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%) within the first two 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.