Pharmacokinetics and pharmacodynamics of 7alpha-methyl-19- nortestosterone after intramuscular administration in healthy men

Abstract

7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that is resistant to 5alpha-reductases and therefore less prone to over-stimulate the prostate. It is a good candidate for implant administration in long-term androgen replacement therapy for hypogonadal men or as part of a male contraceptive system. To investigate the pharmacokinetics of MENT after i.m. administration, single i.m. injections of 2, 4 or 8 mg of micronized MENT were given in aqueous suspension to 18 healthy men in two clinics. Blood was sampled frequently for 8 h and 1, 2, 3, 4 and 9 days after the injections. Serum MENT concentrations were determined by radioimmunoassay. Peak MENT concentrations were dose-dependent and were reached about 1-2 h after the injections. Doubling the dose of MENT resulted in an increase of 60% in peak serum MENT concentrations. The mean +/- SE clearance rate was 1790 +/- 140 l/day. The antigonadotrophic activity of MENT was investigated by giving six consecutive daily i.m. injections of 1, 2 or 4 mg of MENT to 24 healthy men in two clinics. Blood was sampled before each injection and up to 24 days after the last injection. Serum testosterone and gonadotrophin concentrations (determined by radioimmunoassay and fluoroimmunoassay respectively) decreased in a dose-dependent and statistically significant manner. The highest dose caused a 74% fall in testosterone, a 70% fall in luteinizing hormone, and a 57% fall in follicle stimulating hormone concentrations. MENT injections did not cause any side-effects. The results show that MENT is a potent antigonadotrophic agent in men.

A Clinical Trial of 7α-Methyl-19-Nortestosterone Implants for Possible Use as a Long-Acting Contraceptive for Men

“…7␣-Methyl-19-nortestosterone (MENT) is a synthetic androgen that is more potent than T for gonadotropin suppression and is resistant to 5␣-reduction, with potential advantages when used as a contraceptive (15)(16)(17). MENT acetate (Ac) has diffusion characteristics that are well suited for delivery via subdermal implants.…”

Advances in Male Contraception

“…In a study in castrated monkeys, MENT showed a 10-fold greater potency (vs. testosterone) for LH inhibition, but only 2-fold greater potency at stimulating prostate growth (295). In men, MENT has a short half-life, probably due to the fact that MENT does not appear to bind to SHBG (296). Therefore, MENT implants have been synthesized to allow for sustained delivery.…”

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

“…Initial data showed relatively good efficacy, but typical testosteronerelated side effects. Suvisaari et al 53 and others have shown that MENT has a short half-life and is not suitable for long-term injection and does not show significant FSH suppression. Dimethandrolone undecanoate is another potent synthetic androgen with some progestational activity that represents an orally active substance that appears to suppress LH levels in vitro and in rabbit models.…”