Persistent intraprostatic androgen concentrations after medical castration in healthy men.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Page
Stephanie T
ST
University of Washington Medical Center, Division of Metabolism, Endocrinology and Nutrition, Box 357138, 1959 NE Pacific, Seattle, WA 98195. page@u.washington.edu
Lin
Daniel W
DW
Mostaghel
Elahe A
EA
Hess
David L
DL
True
Lawrence D
LD
Amory
John K
JK
Nelson
Peter S
PS
Matsumoto
Alvin M
AM
Bremner
William J
WJ
D000328:Adult; D000728:Androgens / Q000097:blood*; D013196:Dihydrotestosterone / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011467:Prostate / Q000737:chemistry; D017430:Prostate-Specific Antigen / Q000097:blood; D013739:Testosterone / Q000097:blood
D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017430:Prostate-Specific Antigen