TY - JOUR
T1 - Persistent intraprostatic androgen concentrations after medical castration in healthy men
AU - Page, Stephanie T.
AU - Lin, Daniel W.
AU - Mostaghel, Elahe A.
AU - Hess, David L.
AU - True, Lawrence D.
AU - Amory, John K.
AU - Nelson, Peter S.
AU - Matsumoto, Alvin M.
AU - Bremner, William J.
N1 - Funding Information:
This work was supported by the Department of Veterans Affairs Special Fellowship in Advanced Geriatrics (to S.T.P.), the Endocrine Society Solvay Clinical Research Award (to S.T.P.), the National Institute of Child Health and Human Development through cooperative agreements U54-HD-12629 and U54 HD42454, as part of the specialized Cooperative Centers Program in Reproductive Research and the Cooperative Contraceptive Research Centers Program (to J.K.A., A.M.M., and W.J.B.), and National Institutes of Health Grants CA-97186 and DK65204 (to P.S.N), and DK65083 (to D.W.L.), and Oregon National Primate Research Center Core Grant NIH/RR00163 (to D.L.H).
Funding Information:
Disclosure summary: S.T.P., D.W.L., E.A.M., D.L.H., and L.D.T. have nothing to disclose. J.K.A., W.J.B., and A.M.M. have consulted for GlaxoSmithKline. P.S.N. and A.M.M. have consulted for Solvay Pharmaceuticals. J.K.A. has received grant support from GlaxoSmithKline and Schering-Plough. A.M.M. has received grant support from GlaxoSmithKline, Ascend Therapeutics, and Solvay Pharmaceuticals.
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2006-0968
DO - 10.1210/jc.2006-0968
M3 - Article
C2 - 16882745
AN - SCOPUS:33749550602
SN - 0021-972X
VL - 91
SP - 3850
EP - 3856
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -