Persistent intraprostatic androgen concentrations after medical castration in healthy men

Stephanie T. Page, Daniel W. Lin, Elahe A. Mostaghel, David Hess, Lawrence D. True, John K. Amory, Peter S. Nelson, Alvin M. Matsumoto, William J. Bremner

    Research output: Contribution to journalArticle

    166 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)3850-3856
    Number of pages7
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume91
    Issue number10
    DOIs
    StatePublished - Oct 2006

    Fingerprint

    Castration
    Androgens
    Prostate
    Serum
    Dihydrotestosterone
    Hormones
    Tissue
    Prostate-Specific Antigen
    Apoptosis
    Antigen Receptors
    Biopsy
    Cell proliferation
    Androgen Receptors
    Metabolism
    Gonadotropin-Releasing Hormone
    Testosterone
    Volunteers
    Prostatic Neoplasms
    Healthy Volunteers
    Proteins

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Page, S. T., Lin, D. W., Mostaghel, E. A., Hess, D., True, L. D., Amory, J. K., ... Bremner, W. J. (2006). Persistent intraprostatic androgen concentrations after medical castration in healthy men. Journal of Clinical Endocrinology and Metabolism, 91(10), 3850-3856. https://doi.org/10.1210/jc.2006-0968

    Persistent intraprostatic androgen concentrations after medical castration in healthy men. / Page, Stephanie T.; Lin, Daniel W.; Mostaghel, Elahe A.; Hess, David; True, Lawrence D.; Amory, John K.; Nelson, Peter S.; Matsumoto, Alvin M.; Bremner, William J.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 10, 10.2006, p. 3850-3856.

    Research output: Contribution to journalArticle

    Page, ST, Lin, DW, Mostaghel, EA, Hess, D, True, LD, Amory, JK, Nelson, PS, Matsumoto, AM & Bremner, WJ 2006, 'Persistent intraprostatic androgen concentrations after medical castration in healthy men', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 10, pp. 3850-3856. https://doi.org/10.1210/jc.2006-0968
    Page, Stephanie T. ; Lin, Daniel W. ; Mostaghel, Elahe A. ; Hess, David ; True, Lawrence D. ; Amory, John K. ; Nelson, Peter S. ; Matsumoto, Alvin M. ; Bremner, William J. / Persistent intraprostatic androgen concentrations after medical castration in healthy men. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 10. pp. 3850-3856.
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    abstract = "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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    AU - Page, Stephanie T.

    AU - Lin, Daniel W.

    AU - Mostaghel, Elahe A.

    AU - Hess, David

    AU - True, Lawrence D.

    AU - Amory, John K.

    AU - Nelson, Peter S.

    AU - Matsumoto, Alvin M.

    AU - Bremner, William J.

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    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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