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The Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2010-1865
J Clin Endocrinol Metab, Vol. 96 (2): 430-437
Dihydrotestosterone Administration Does Not Increase Intraprostatic Androgen Concentrations or Alter Prostate Androgen Action in Healthy Men: A Randomized-Controlled Trial
Stephanie T. Page, Daniel W. Lin, Elahe A. Mostaghel, Brett T. Marck, Jonathan L. Wright, Jennifer Wu, John K. Amory, Peter S. Nelson and Alvin M. Matsumoto
Department of Medicine (S.T.P., E.A.M., J.W., J.K.A., P.S.N., A.M.M.) and Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L.) and Division of Human Biology and Clinical Research (E.A.M., P.S.N.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; and Geriatric Research, Education, and Clinical Center and Department of Medicine (B.T.M., A.M.M.), V.A. Puget Sound Health Care System, Seattle, Washington 98108
Address all correspondence and requests for reprints to: Dr. Stephanie T. Page, M.D., Ph.D., Associate Professor, Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Box 357138, 1959 NE Pacific Street, Seattle, Washington 98195. E-mail: page@u.washington.edu.
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 5-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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The Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2010-1865
J Clin Endocrinol Metab, Vol. 96 (2): 430-437
Dihydrotestosterone Administration Does Not Increase Intraprostatic Androgen Concentrations or Alter Prostate Androgen Action in Healthy Men: A Randomized-Controlled Trial
Stephanie T. Page, Daniel W. Lin, Elahe A. Mostaghel, Brett T. Marck, Jonathan L. Wright, Jennifer Wu, John K. Amory, Peter S. Nelson and Alvin M. Matsumoto
Department of Medicine (S.T.P., E.A.M., J.W., J.K.A., P.S.N., A.M.M.) and Department of Urology (D.W.L., J.L.W.), University of Washington, Seattle, Washington 98195; Division of Public Health Sciences (D.W.L.) and Division of Human Biology and Clinical Research (E.A.M., P.S.N.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; and Geriatric Research, Education, and Clinical Center and Department of Medicine (B.T.M., A.M.M.), V.A. Puget Sound Health Care System, Seattle, Washington 98108
Address all correspondence and requests for reprints to: Dr. Stephanie T. Page, M.D., Ph.D., Associate Professor, Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Box 357138, 1959 NE Pacific Street, Seattle, Washington 98195. E-mail: page@u.washington.edu.
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 5-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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