Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone

Abstract

Context: Concern exists that T replacement therapy (TRT) might increase the risk of prostate disease. There are limited data regarding the impact of TRT on prostate androgen concentrations.

Objective: Determine the dose-dependent effects of exogenous T administration on intraprostatic androgen concentrations.

Design: Twelve-week, double-blinded, randomized, placebo-controlled trial.

Setting: Academic medical center.

Participants: Sixty-two healthy eugonadal men, aged 25-55 years.

Interventions: Subjects were randomly assigned to receive injections of acyline, a GnRH antagonist (used to achieve medical castration), every 2 weeks plus transdermal T gel (1.25 g, 2.5 g, 5.0 g, 10 g, or 15 g daily), or placebo injections and transdermal gel for 12 weeks.

Main outcomes: Serum T and dihydrotestosterone (DHT) were measured at baseline and every 2 weeks during treatment. Intraprostatic T and DHT concentrations were assessed from tissue obtained through ultrasound-guided prostate needle biopsies at week 12. Androgens were quantified by liquid chromatography-tandem mass spectrometry.

Results: 51 men completed the study and were included in the analysis. There were no significant adverse events. Exogenous T resulted in a dose-dependent increase in serum T and DHT concentrations (190-770 and 60-180 ng/dL, respectively). Although intraprostatic T differed among dose groups (P = .01), intraprostatic DHT was comparable regardless of T dose (P = .11) and was 10- to 20-fold greater than intraprostatic T.

Conclusions: In healthy, medically castrate men receiving exogenous T, the total intraprostatic androgen concentration (predominantly DHT) remained stable across serum T concentrations within the physiological range. These findings further our knowledge of the relationship between serum and intraprostatic androgens and suggest that physiological serum T achieved by TRT is unlikely to alter the prostate hormonal milieu.

Trial registration: ClinicalTrials.gov NCT01327495.

Figures

Figure 1.

Serum T (A) and serum DHT (B) concentrations during treatment (weeks 2–12) and intraprostatic T (C) and intraprostatic DHT (D) concentrations at the end of treatment (week 12). White solid lines represent medians. Black hashed lines represent normal reference ranges. Significant differences are denoted as relative to 15 g T (*), 10 g T (#), 5 g T ($), and 2.5 g T (Ω) groups, respectively. ng/g, nanograms per gram of prostate tissue.

Figure 2.

Hematocrit (%) at the end of treatment (week 12). *, Significant differences relative to 15-g T group.