Prostate-sparing effects in primates of the potent androgen 7 alpha-methyl-19-nortestosterone: A potential alternative to testosterone for androgen replacement and male contraception

7 alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen tha t cannot be converted to dihydrotestosterone. In this study we determined t he relative androgenic, antigonadotropic, and anabolic potencies of testost erone vs. MENT in the nonhuman primate M. fascicularis. In castrated monkey s, dose-response relationships were generated for the effects of testostero ne and MENT on gonadotropin levels, prostate growth, body weight, and lipid metabolism. In a pilot study, four monkeys were castrated, and magnetic re sonance imaging (MRI) was used to document a 50% loss of prostate volume wi thin 8 weeks, verifying that MRI is a reliable means to measure prostate si ze in this species. Two additional groups of six monkeys each mere then cas trated and serially administered four graded dosages of testosterone or MEN T via osmotic minipumps over 20 weeks. Complete suppression of LH was achie ved with a minimum of 0.3 mg/day MENT, compared to 3.0 mg/day testosterone. MENT supported body weight 10 times more potently than did testosterone. B aseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3 m g/day testosterone. Thus, in monkeys, MENT is 10 times more potent than tes tosterone with regard to the clinically desirable end points of gonadotropi n suppression and anabolism, but only twice as potent at stimulating prosta te growth. These results suggest that MENT may have a wider therapeutic ind ex than testosterone for human androgen replacement and male contraception.