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Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial.

Author(s): Page ST, Lin DW, Mostaghel EA, Marck BT, Wright JL, Wu J, Amory JK, Nelson PS, Matsumoto AM

Affiliation(s): Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Box 357138, 1959 NE Pacific Street, Seattle, Washington 98195, USA. page@u.washington.edu

Publication date & source: 2011-02, J Clin Endocrinol Metab., 96(2):430-7. Epub 2010 Dec 22.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

CONTEXT: Concern exists that androgen treatment might adversely impact prostate health in older men. Dihydrotestosterone (DHT), derived from local conversion of testosterone to DHT by 5alpha-reductase enzymes, is the principal androgen within the prostate. Exogenous androgens raise serum DHT concentrations, but their effects on the prostate are not clear. OBJECTIVE: To determine the impact of large increases in serum DHT concentrations on intraprostatic androgen concentrations and androgen action within the prostate. DESIGN: Double-blind, randomized, placebo-controlled. SETTING: Single academic medical center. PARTICIPANTS: 31 healthy men ages 35-55. INTERVENTION: Daily transdermal DHT or placebo gel. MAIN OUTCOME MEASURES: Serum and prostate tissue androgen concentrations and prostate epithelial cell gene expression after 4 wk of treatment. RESULTS: Twenty-seven men completed all study procedures. Serum DHT levels increased nearly sevenfold, while testosterone levels decreased in men treated with daily transdermal DHT gel but were unchanged in the placebo-treated group (P < 0.01 between groups). In contrast, intraprostatic DHT and testosterone concentrations on d 28 were not different between groups (DHT: placebo = 2.8 +/- 0.2 vs. DHT gel = 3.1 +/- 0.5 ng/g; T: placebo = 0.6 +/- 0.2 vs. DHT gel = 0.4 +/- 0.1, mean +/- se). Similarly, prostate volume, prostate-specific antigen, epithelial cell proliferation, and androgen-regulated gene expression were not different between groups. CONCLUSIONS: Robust supraphysiologic increases in serum DHT, associated with decreased serum T, do not significantly alter intraprostatic levels of DHT, testosterone, or prostate epithelial cell androgen-regulated gene expression in healthy men. Changes in circulating androgen concentrations are not necessarily mimicked within the prostate microenvironment, a finding with implications for understanding the impact of androgen therapies in men.

Page last updated: 2011-12-09

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