Evidence for Tissue Selectivity of the Synthetic Androgen 7α-Methyl-19-Nortestosterone in Hypogonadal Men

Abstract

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.

Effects of androgen substitution on lipid profile in the adult and aging hypogonadal male

“…A comparative study (68) shows that the MENT implants were well tolerated and preferred to the frequent injection of testosterone enanthate. A recent abstract showed a decrease in prostate volume while muscle mass increased (69). More data are needed for further evaluation of the clinical effects and long-term safety of MENT, in particular on plasma lipids.…”

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

“…Indeed, in contrast to testosterone, MENT is less potent on male accessory sex glands compared with its ability to suppress gonadotropins; MENT otherwise can be aromatized to 7a-methyl-E 2 (LaMorte et al 1994). These observations indicate that MENT, as a component for androgen replacement therapy or male contraceptive, has health-promoting effects, particularly by avoiding hyperstimulative effects on the prostate, including prostatespecific antigen (Kumar et al 1992, Morali et al 1993, Cummings et al 1998, Anderson et al 2003, von Eckardstein et al 2003, Walton et al 2007, and those derived from MENT aromatization (LaMorte et al 1994, Anderson et al 1999.…”

Dihydrotestosterone is a determinant of calcaneal bone mineral density in men

“…Anderson et al [21] demonstrated a significant decrease in BMD at the lumbar spine when hypogonadal men were administered with 7␣-methyl-19-nortestosterone (MENT), while testosterone treatment demonstrated no significant change but maintained the lumbar spine BMD. MENT is a potent synthetic androgen that is resistant to 5␣-reduction, but can be converted by the aromatase to an active estrogen [22].…”