Comparison Between Testosterone Enanthate‐Induced Azoospermia and Oligozoospermia in a Male Contraceptive Study. V. Localization of Higher 5α‐Reductase Activity to the Reproductive Tract in Oligozoospermie Men Administered Supraphysiological Doses of Testosterone

Abstract

ABSTRACT: Sex steroid contraceptive regimens result in incomplete suppression of spermatogenesis in 30–45% of Caucasian men. The basis for this is unclear, but differences in the activity of 5α‐reductase (5αR) have been demonstrated. Two isoforms of 5αR have been described: 5αR1 is found in skin, whereas the predominant form in reproductive tissues is 5αR2. To investigate possible contributions of these isoenzymes, we have investigated androgen‐dependent changes in seminal plasma androgens (5αR2) and sebum production (5αR1) during administration of a supraphysiological dose (200 mg IM weekly) of testosterone enanthate (TE) to 33 normal men.Eighteen men rapidly (<20 weeks treatment) became azoospermia, the remainder having a mean sperm density of 2.0 ± 0.6 × 106 at that time. The concentrations of testosterone and 3α, 17β‐andros‐tanediol glucuronide (AdiolG) were lower in seminal plasma than in blood but rose by a similar degree (100%) after 16 weeks TE treatment in both groups. There were no differences in seminal‐plasma concentration of testosterone or AdiolG between azoospermic and Oligozoospermie responders, either pretreatment or after 16 weeks TE treatment. Although the concentrations of dihydrotestosterone (DHT) were similar in seminal plasma and blood pre‐ and posttreatment, there was a selective increase in seminal plasma DHT concentration in the Oligozoospermie responders from 2.12 ± 0.29 to 2.94 ± 0.33 nmol/L (P < 0.05), while there was no significant change in the azoospermic responders (2.18 ± 0.31–2.54 ± 0.27 nmol/L) after 16 weeks of TE treatment. Dihydrotestosterone in seminal plasma is primarily derived from 5αR activity in the epididymis. The concentration of prostaglandin E2 (PGE2) in seminal plasma was unchanged during TE treatment. Sebum excretion was increased during TE treatment, but there were no differences between azoospermic and Oligozoospermie responders pretreatment or after 16 weeks TE treatment. These results are consistent with the hypothesis that incomplete suppression of spermatogenesis during TE treatment is associated with a relatively higher 5αR activity in the reproductive tract (epididymis and/or testis) during TE treatment. As the predominant form of 5αR in the reproductive tract is 5αR2 (type 2), we conclude that the increase in activity derives from this form of the enzyme, rather than the type 1 form (5αR1) predominantly found in nongenital skin.