Prostate-sparing effects in primates of the potent androgen 7alpha-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception.
7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that cannot be converted to dihydrotestosterone. In this study we determined the relative androgenic, antigonadotropic, and anabolic potencies of testosterone vs. MENT in the nonhuman primate M. fascicularis. In castrated monkeys, dose-response relationships were generated for the effects of testosterone and MENT on gonadotropin levels, prostate growth, body weight, and lipid metabolism. In a pilot study, four monkeys were castrated, and magnetic resonance imaging (MRI) was used to document a 50% loss of prostate volume within 8 weeks, verifying that MRI is a reliable means to measure prostate size in this species. Two additional groups of six monkeys each were then castrated and serially administered four graded dosages of testosterone or MENT via osmotic minipumps over 20 weeks. Complete suppression of LH was achieved 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. Baseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3 mg/day testosterone. Thus, in monkeys, MENT is 10 times more potent than testosterone with regard to the clinically desirable end points of gonadotropin suppression and anabolism, but only twice as potent at stimulating prostate growth. These results suggest that MENT may have a wider therapeutic index than testosterone for human androgen replacement and male contraception.
Cummings
D E
DE
University of Washington School of Medicine, Veterans Affairs, Puget Sound Health Care System, Seattle 98108, USA.
Kumar
N
N
Bardin
C W
CW
Sundaram
K
K
Bremner
W J
WJ
D045930:Anabolic Agents / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020249:Hormone Replacement Therapy; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009919:Orchiectomy; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use
D045930:Anabolic Agents; D000728:Androgens; D003272:Contraceptive Agents, Male; D013739:Testosterone; C064709:trestolone; D009277:Nandrolone; D007986:Luteinizing Hormone