RT Journal
A1 Marks LS, Mazer NA, Mostaghel E, et al
T1 Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: A randomized controlled trial
JF JAMA
JO JAMA
YR 2006
FD November 15
VO 296
IS 19
SP 2351
OP 2361
DO 10.1001/jama.296.19.2351
UL http://dx.doi.org/10.1001/jama.296.19.2351
AB Context 
                  Prostate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men.Objective 
                  To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels.Design, Setting, and Participants 
                  Randomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (<10.4 nmol/L) and related symptoms, conducted at a US community-based research center between February 2003 and November 2004.Intervention 
                  Participants were randomly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months.Main Outcome Measures 
                  The primary outcome measure was the 6-month change in prostate tissue androgen levels (testosterone and dihydrotestosterone). Secondary outcome measures included 6-month changes in prostate-related clinical features, histology, biomarkers, and epithelial cell gene expression.Results 
                  Of the 44 men randomized, 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per-protocol analysis (TRT, n = 21; placebo, n = 19). Testosterone replacement therapy increased serum testosterone levels to the mid-normal range (median at baseline, 282 ng/dL [9.8 nmol/L]; median at 6 months, 640 ng/dL [22.2 nmol/L]) with no significant change in serum testosterone levels in matched, placebo-treated men. However, median prostate tissue levels of testosterone (0.91 ng/g) and dihydrotestosterone (6.79 ng/g) did not change significantly in the TRT group. No treatment-related change was observed in prostate histology, tissue biomarkers (androgen receptor, Ki-67, CD34), gene expression (including AR, PSA, PAP2A, VEGF, NXK3, CLU [Clusterin]), or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were minor.Conclusions 
                  These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study.Trial Registration 
                  clinicaltrials.gov Identifier: NCT00161304