This Article Full Text Full Text (PDF) All Versions of this Article: 91/10/3850    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Page, S. T. Articles by Bremner, W. J. Search for Related Content PubMed PubMed Citation Articles by Page, S. T. Articles by Bremner, W. J. Related Collections Male Endocrinology

Persistent Intraprostatic Androgen Concentrations after Medical Castration in Healthy Men

Departments of Medicine (S.T.P., E.A.M., J.K.A., P.S.N., A.M.M., W.J.B.), Urology (D.W.L.), and Pathology (L.D.T.), University of Washington School of Medicine, Seattle, Washington 98195; Veterans Affairs Puget Sound Health Care System (S.T.P., D.W.L., A.M.M.), and Geriatric Research, Education and Clinical Center (A.M.M.), Seattle, Washington 98108; Oregon National Primate Research Center (D.L.H.), Oregon Health & Science University West Campus, Beaverton, Oregon 97006; and Divisions of Human Biology and Clinical Research (P.S.N.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024

Address all correspondence and requests for reprints to: Stephanie T. Page, University of Washington Medical Center, Division of Metabolism, Endocrinology and Nutrition, Box 357138, 1959 NE Pacific, Seattle, Washington 98195. E-mail: page{at}u.washington.edu.

Context: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences.

Objective: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men.

Design: Thirteen male volunteers ages 35–55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone (T) gel (10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed.

Results: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls (P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression.

Conclusion: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20–30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study.

This article has been cited by other articles:

				R. B. Montgomery, E. A. Mostaghel, R. Vessella, D. L. Hess, T. F. Kalhorn, C. S. Higano, L. D. True, and P. S. Nelson Maintenance of Intratumoral Androgens in Metastatic Prostate Cancer: A Mechanism for Castration-Resistant Tumor Growth Cancer Res., June 1, 2008; 68(11): 4447 - 4454. [Abstract] [Full Text] [PDF]

				S. R. Plymate, K. Haugk, I. Coleman, L. Woodke, R. Vessella, P. Nelson, R. B. Montgomery, D. L. Ludwig, and J. D. Wu An Antibody Targeting the Type I Insulin-like Growth Factor Receptor Enhances the Castration-Induced Response in Androgen-Dependent Prostate Cancer Clin. Cancer Res., November 1, 2007; 13(21): 6429 - 6439. [Abstract] [Full Text] [PDF]

				E. B. Askew, R. T. Gampe Jr., T. B. Stanley, J. L. Faggart, and E. M. Wilson Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone J. Biol. Chem., August 31, 2007; 282(35): 25801 - 25816. [Abstract] [Full Text] [PDF]

				S. A. Hall, S. T. Page, T. G. Travison, R. B. Montgomery, C. L. Link, and J. B. McKinlay Do Statins Affect Androgen Levels in Men? Results from the Boston Area Community Health Survey Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1587 - 1594. [Abstract] [Full Text] [PDF]

				E. A. Mostaghel, S. T. Page, D. W. Lin, L. Fazli, I. M. Coleman, L. D. True, B. Knudsen, D. L. Hess, C. C. Nelson, A. M. Matsumoto, et al. Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for Castration-Resistant Prostate Cancer Cancer Res., May 15, 2007; 67(10): 5033 - 5041. [Abstract] [Full Text] [PDF]