Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated with Exogenous Testosterone.

Abstract:

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

OBJECTIVE: Determine the dose-dependent effects of exogenous testosterone (T) administration on intraprostatic androgen concentrations.

DESIGN: 12-week, double-blinded, randomized, placebo-controlled trial.

SETTING: Academic medical center Participants: 62 healthy eugonadal men, aged 25-55 years.

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

MAIN OUTCOMES: Serum T and 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 LC-MS/MS.

RESULTS: 51 men completed the study and were included in analysis. There were no significant adverse events. Exogenous T resulted in dose-dependent increase in serum T and DHT concentrations (190-770 and 60-180 ng/dL, respectively). While intraprostatic T differed among dose groups (p=0.01), intraprostatic DHT was comparable regardless of T dose (p=0.11) and 10-20-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 physiologic range. These findings further our knowledge of the relationship between serum and intraprostatic androgens and suggest physiologic serum T achieved by TRT is unlikely to alter the prostate hormonal milieu.