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

J Clin Endocrinol Metab

Department of Medicine (A.T., K.B.R., J.K.A., A.M.M., S.T.P.), University of Washington, Seattle, Washington 98195; Endocrinology (L.A.C.), The Polyclinic, Seattle, Washington 98122; Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L., J.L.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Geriatric Research (B.T.M., A.M.M.), Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 98108; Division of Gerontology and Geriatric Medicine (A.M.M.), Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195.

Published: July 2016

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929843PMC
http://dx.doi.org/10.1210/jc.2016-1483DOI Listing

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