Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception

Recent trials for hormonal male contraception are based on gestagens or GnR H antagonists combined with oral or injectable testosterone substitution. H owever, the efficacy of most trials remained disappointing. Noretkisterone enanthate (NETE) has been used as a long-acting injectable female contracep tive and has shown sustained suppression of spermatogenesis in male monkeys and prolonged suppression of gonadotropins in men. This study was designed to prove the efficacy of the long-acting testosterone undecanoate ester (T U) alone or in combination with NETE in a phase II clinical trial. Fourteen healthy men received injections of 1000 mg TU in combination with injectio ns of 200 mg NETE every 6 weeks over a period of 24 weeks, followed by a co ntrol period of 28 weeks. Another 14 volunteers received TU alone. During t he study semen variables, reproductive hormones, clinical chemistry and lip id parameters, well-being, and sexual function were monitored. Scrotal cont ent and prostates were checked sonographically. During the entire treatment period mean testosterone serum concentrations remained within the normal l imits. Marked suppression of gonadotropins in both treatment groups resulte d in azoospermia in 7 of 14 and 13 of 14 volunteers and in oligozoospermia in 7 of 14 and 1 of 14 in the groups given TU only or TU/NETE, respectively . However, the highest azoospermia rate in the TU/NETE group was achieved 8 weeks after the end of the treatment period, and 1 volunteer with very hig h initial sperm counts (mean, 190 million/mL at baseline) remained oligozoo spermic (10.2 million/mL). From week 20 to week 24 there was a significant, fully reversible maximum weight gain of 3.7 kg, on the average, in the NET E group. In the NETE and TU alone groups there were significant 26.6% and 1 1.5% maximum decreases in high density lipoprotein cholesterol compared wit h baseline values during the treatment period. A significant elevation of l ow density lipoprotein and a decrease in lipoprotein(a) were detected in th e TU/NETE group. In conclusion, combination treatment with NETE showed supp ression of spermatogenesis comparable with results using testosterone ester s in combination with GnRH antagonists or cyproterone acetate, but had more favorable injection intervals and better efficacy. Because of its long-las ting, profound suppression of spermatogenesis and the absence of serious si de-effects, the combination of TU and NETE can be considered a first choice for further studies of hormonal male contraception.