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.

强效合成雄激素7α - 甲基 - 19 - 去甲睾酮（MENT）对5α - 还原酶有抗性，但却是芳香化酶的底物。因此，它可能在支持其他雄激素依赖组织的同时，对前列腺有选择性的保护作用。对16名性腺功能减退男性给予MENT醋酸酯植入物，持续24周，随机分为1个或2个植入物组（分别为I组和II组；每个植入物约释放400微克/天）。在MENT治疗期间，血红蛋白浓度和血细胞比容得以维持。I组前列腺体积减小，II组前列腺体积也有少量减小，但无统计学意义；两组的前列腺特异性抗原水平均显著下降。两组的腰椎骨矿物质密度均下降。I组性行为和勃起功能下降，但II组得以维持。因此，总体而言，一个MENT植入物似乎提供了亚生理水平的雄激素替代。MENT的2个植入物剂量能够维持大多数雄激素依赖性功能，但骨量除外，并且有证据支持对前列腺的选择性保护。这些结果首次在人类中证明了MENT在依赖5α - 还原酶的组织中的选择性。此外，我们的数据与足够的雌激素活性作为男性替代治疗中雄激素必要活性谱的一部分的重要性是一致的。