Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men.
The potent synthetic androgen 7 alpha-methyl-19-nortestosterone (MENT) is resistant to 5 alpha-reductase but is a substrate for aromatase. It may therefore offer selective sparing of the prostate gland while supporting other androgen-dependent tissues. MENT acetate implants were administered for 24 wk to 16 hypogonadal men, randomly allocated to 1 or 2 implants (groups I and II, respectively; releasing approximately 400 microg/d x implant). Hemoglobin concentration and hematocrit were maintained during MENT treatment. Prostate volume fell in group I and to a small, but statistically nonsignificant, degree in group II; the level of prostate-specific antigen fell significantly in both. Lumbar spine bone mineral density decreased in both groups. Sexual behavior and erectile function declined in group I, but were maintained in group II. Thus, overall, one MENT implant appeared to provide subphysiological androgen replacement. The 2-implant dose of MENT was able to maintain most androgen-dependent functions, except bone mass, and there was evidence to support selective sparing of the prostate gland. These results demonstrate for the first time in humans the selectivity of MENT in tissues dependent on 5 alpha-reductase. In addition, our data are consistent with the importance of adequate estrogenicity as part of the necessary spectrum of activity of an androgen for replacement therapy in men.
Anderson
Richard A
RA
Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh, Edinburgh, United Kingdom EH16 4SB. r.a.anderson@hrsu.mrc.ac.uk
Wallace
A Michael
AM
Sattar
Naveed
N
Kumar
Narendar
N
Sundaram
Kalyan
K
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001823:Body Composition; D001835:Body Weight; D015519:Bone Density; D016723:Bone Remodeling; D004334:Drug Administration Schedule; D004343:Drug Implants; D004920:Erythropoiesis; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009640:Norethindrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D009929:Organ Size; D011467:Prostate / Q000000981:diagnostic imaging; D017430:Prostate-Specific Antigen / Q000097:blood; D012725:Sexual Behavior; D013739:Testosterone / Q000097:blood; D014018:Tissue Distribution; D014463:Ultrasonography
C421822:7-methyl-norethisterone; D015415:Biomarkers; D004343:Drug Implants; D008074:Lipoproteins; D013739:Testosterone; D017430:Prostate-Specific Antigen; D009640:Norethindrone