TY - JOUR
T1 - Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men
T2 - A randomized-controlled trial
AU - Page, Stephanie T.
AU - Lin, Daniel W.
AU - Mostaghel, Elahe A.
AU - Marck, Brett T.
AU - Wright, Jonathan L.
AU - Wu, Jennifer
AU - Amory, John K.
AU - Nelson, Peter S.
AU - Matsumoto, Alvin M.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2010-1865
DO - 10.1210/jc.2010-1865
M3 - Article
C2 - 21177791
AN - SCOPUS:79951714359
SN - 0021-972X
VL - 96
SP - 430
EP - 437
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 2
ER -
