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

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.

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

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

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

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.

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.

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.

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.

The Journal of clinical endocrinology and metabolism. 2016 May 12 [Epub ahead of print]

Arthi Thirumalai, Lori A Cooper, Katya B Rubinow, John K Amory, Daniel W Lin, Jonathan L Wright, Brett T Marck, Alvin M Matsumoto, Stephanie T Page

Department of Medicine, University of Washington, Seattle, WA, USA.;, Endocrinology, The Polyclinic, Seattle, WA.;, Department of Medicine, University of Washington, Seattle, WA, USA.;, Department of Medicine, University of Washington, Seattle, WA, USA.;, Department of Urology, University of Washington, Seattle, WA, USA.;, Department of Urology, University of Washington, Seattle, WA, USA.;, Geriatric Research, Education and Clinical Center, V.A. Puget Sound Health Care System, Seattle, WA, USA;, Department of Medicine, University of Washington, Seattle, WA, USA.;, Department of Medicine, University of Washington, Seattle, WA, USA.;

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