Norethisterone Enanthate Plus Testosterone Undecanoate for Male Contraception: Effects of Various Injection Intervals on Spermatogenesis, Reproductive Hormones, Testis, and Prostate

Abstract

The goal of this study was to find the most favorable injection interval of norethisterone enanthate (NETE) plus testosterone undecanoate (TU) in terms of gonadotropin, sperm suppression, and prostatic effects. Fifty normal men were randomly assigned to receive NETE 200 mg plus TU 1000 mg every 8 wk (n = 10), every 12 wk (n = 10), every 6 wk for 12 wk and then every 12 wk (n = 10), and every 6 wk for 12 wk and thereafter TU 1000 mg plus placebo every 12 wk (n = 10), and placebo plus placebo every 6 wk for 12 wk and then every 12 wk (n = 10) for 48 wk. Semen analyses, blood drawings, physical examinations, and prostate ultrasounds were performed throughout the study. Of the men in the 8-wk injection group, 90% (nine of 10) achieved azoospermia, compared with 37.5% (three of eight) in the 12-wk injection group (P = 0.019). TU plus placebo injected every 12 wk did not maintain sperm suppression. Prostate volumes did not change significantly in either group. In conclusion, these data suggest that the combined administration of NETE and TU at 8-wk intervals represents an effective hormonal contraceptive regimen.

Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus)

“…Concluding our findings, the marmoset is a NHP model that would facilitate the measurement of fertility as an endpoint in a contraceptive trial but is obviously resistant to TU and NETE, which were shown to be effective suppressors of spermatogenesis in humans (Kamischke et al 2002, Kamischke & Nieschlag 2004, Meriggiola et al 2005. Although testicular volumes dropped and the endocrine axis responded as expected, fertility was, if at all, only mildly influenced by the administration of androgens and progestins and a reliable contraceptive effect of TU and NETE treatment is lacking in this animal model.…”

“…Concerning testosterone, the permanent presence of enhanced levels could result in a certain resistance in the target organs (Takahashi et al 1985, Li et al 2005 and an accelerated clearance of exogenous androgens was reported (Mohle et al 2002, reviewed in Li et al (2005). Owing to this specific endocrine condition, we adapted the dosing of TU in our experiments and administered w3.5-fold higher dose compared with the amount recommended for human use (Kamischke et al 2001, Meriggiola et al 2005. However, before our experiments were performed, no experience existed about effects of TU/NETE on spermatogenesis in NHP species.…”

Comparison of 7α-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation

“…Four MENT implants induced azoospermia or severe oligozoospermia (sperm count !1!10 6 /ml) in 82% and 100% of subjects during the first and second 6-month periods of treatment respectively. Thus, during the last 6 months of treatment, MENT alone was as effective as testosterone undecanoate plus NET enanthate administered at 8-week intervals (Meriggiola et al 2005).…”

“…A number of studies have shown that combination of androgens and androgenic progestins such as levonorgestrel (LNG), etonogestrel (ENG), and norethisterone (NET), which are all 19-nortestosterone derivatives, increases the rate of azoospermia. This combined method allows reduction of the high dose of testosterone needed to suppress gonadotropins and its secondary adverse effects, while maintaining the beneficial peripheral actions of testosterone and, therefore, its potential utility as a male contraceptive (Meriggiola & Bremner 1997, Anderson & Baird 2002, Meriggiola et al 2005, Walton et al 2007). Although it is well known that some progestins can effectively suppress gonadotropin secretion and have a direct inhibitory effect on Leydig cell steroidogenesis, it remains to be seen whether the hormonal combination has an additive agonist-antagonist androgenic effect.…”

Update on Male Hormonal Contraception: Is the Vasectomy in Jeopardy?

“…norethisterone and TU. 83,84 8-week intervals of treatment had a higher azoospermic rate than 12-week treatment. No short-term changes in the prostate were seen.…”