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J Clin Endocrinol Metab. 2011 Feb;96(2):430-7. doi: 10.1210/jc.2010-1865. Epub 2010 Dec 22.

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

Author information

1
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

Abstract

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 5α-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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00490022.

PMID:
21177791
PMCID:
PMC3048323
DOI:
10.1210/jc.2010-1865
[Indexed for MEDLINE]
Free PMC Article

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