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Submitted on May 5, 2006
Accepted on July 25, 2006
Departments of Medicine (S.T.P., E.A.M., J.K.A., P.S.N., A.M.M., W.J.B.), and Urology (D.W.L), and Pathology (L. D. T.), University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA, 98195, Veterans Affairs Puget Sound Health Care System (S.T.P., D.W.L., A.M.M.), and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System (A.M.M.), 1660 S Columbian Way, Seattle, WA, 98108, Oregon National Primate Research Center (D.L.H.), OHSU West Campus, 505 NW 185th Ave, Beaverton Oregon, 97006, and Divisions of Human Biology and Clinical Research (P.S.N), Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, 98109-1024, Seattle, Washington
* To whom correspondence should be addressed. 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: To determine the effect of serum androgen manipulation on intraprostatic androgens in normal men.
Design: 13 male volunteers ages 35-55 (PSA<2.0 ng/ml, normal trans-rectal ultrasound) were randomly assigned to 1) a long-acting GnRH-antagonist, acyline, every 2 weeks, 2) acyline plus testosterone (T) gel (10 mg/day), or 3) placebo for 28 days. Serum hormones were assessed weekly. Prostate biopsies were obtained on Day 28. Extracted androgens were measured by radioimmunoassay (RIA), and immunohistochemistry for androgen-regulated proteins was performed.
Results: The mean decrease in serum T was 94% while prostatic T and DHT 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, PSA 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 DHT 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.
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