Body Fat Content and Testosterone Pharmacokinetics Determine Gonadotropin Suppression After Intramuscular Injections of Testosterone Preparations in Normal Men

Abstract

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 6 0.6 vs 11.3 6 0.6 mg/kg; P 5 NS) and reached higher maximal concentrations of total T (40 6 4.8 vs 18.4 6 2.4 nmol/L; P , .001) and free T as well as estradiol. Men with high fat mass (mean 6 SEM, 10.3 6 1.5 vs 23.2 6 6.4 kg) had a delayed increase in T levels and an impaired relative decline in LH (12 6 2% vs 53 6 10%) and FSH (17 6 6%. vs 70 6 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.

Male contraception: a clinically-oriented review

“…Recent studies indicate that non-responders presented higher levels of Insulin-like Growth Factor-3 (IGF-3, a marker of leydig cell function) during MHC, but a causal relationship could not be established. 70 Additionally, it was shown that obese men with higher fat mass were more likely to be non-responders, 71 a drawback that could possibly be overcome by adjusting the dose of androgens according to weight and body composition. Finally, genetic polymorphisms in the first exon of the androgen receptor, in particular the increased number of iterations of the trinucleotide CAG, are associated with reduced sensitivity to androgens and, therefore, reduced efficacy as MHC.…”

Male Hormonal Contraception

“…4 Percentage of 333 men with sperm concentration below or equal to different cut of levels, participating in a double-blind, randomized, placebo-controlled multicentre trial using various combinations of etonogestrel implants and testosterone undecanoate injections (from Mommers et al 2008) In early clinical trials for male contraception, analysis of anthropometric characteristics failed to contribute to solving the responder:nonresponder problem. However, recently the importance of body fat for the suppressibility of gonadotropins has been emphasized (Kornmann et al 2009). When 40 healthy volunteers receiving equal doses of testosterone undecanoate intramuscularly were divided into groups according to their suppression of gonadotropins, those with consistent suppression had the lowest body fat content (10.3 AE 1.5 kg) and those with no suppression had the highest fat content (23.2 AE 6.4 kg).…”

Hormonal, chemical and thermal inhibition of spermatogenesis: contribution of French teams to international data with the aim of developing male contraception in France

“…Several explanations have been put forward to explain the unsuccessful outcomes of hormonal treatments: they bear on the hypothalamic-pituitary control of spermatogenesis [36–40], testosterone activation by 5-alpha reductase [41], germ cell apoptosis [42, 43], specific diet [44] and adipose tissue excess [45]. …”