Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism: A Randomized Controlled Trial
Abstract
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 ( 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…
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There is accumulating evidence against a link between testosterone therapy and prostate cancer development.
“there is accumulating evidence against a link between testosterone therapy and prostate cancer development.”
From Evaluation and Management of Testosterone Deficiency: AUA Guideline (2018) · cites this paper as [34]
Randomized controlled trials have shown no significant increase in the rate of prostate cancer diagnosis in older, testosterone deficient men treated with testosterone compared to placebo.
“Randomized controlled trials have shown that there is not a significant increase in the rate of a prostate cancer diagnosis in older, testosterone deficient men who were treated with testosterone compared to placebo.”
From Evaluation and Management of Testosterone Deficiency: AUA Guideline (2018) · cites this paper as [34]
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References 54 · Cited by 400
- Authors
- Marks, L. S., Mazer, N. A., Mostaghel, E., Hess, D. L., Dorey, F. J., Epstein, J. I., Veltri, R. W., Makarov, D. V., Partin, A. W., Bostwick, D. G., Macairan, M. L., & Nelson, P. S.
- Affiliations
- University of California, Los Angeles (US)
- Boston University (US)
- University of Washington (US)
- Oregon Health & Science University (US)
- University of Southern California (US)
- Johns Hopkins University (US)
- Bostwick Laboratories (US)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2006-11-15
- Volume
- 296
- Issue
- 19
- Pages
- 2351
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2113645951
- Cited by
- 400
- References
- 54
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 13 · 2023: 9 · 2022: 16 · 2021: 12 · 2020: 17 · 2019: 17 · 2018: 10 · 2017: 17 · 2016: 19 · 2015: 30 · 2014: 31 · 2013: 28 · 2012: 30
- FWCI
- 18.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 97186, P50CA058236, P50-CA58236, P50CA097186)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065204, DK65204)
- National Center for Research Resources (RR-00163.)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Keywords
- testosterone replacement therapy, andropause, prostate tissue, testosterone enanthate, dihydrotestosterone, prostate-specific antigen, prostate histology, androgen receptor, prostate cancer risk, older men, prostate volume, urine flow, voiding symptoms, clusterin, vascular endothelial growth factor, prostatic acid phosphatase
- MeSH terms
- Adult, Aged, Biopsy, Needle, Double-Blind Method, Epithelial Cells, Humans, Hypogonadism, Male, Middle Aged, Prostate, Prostatic Neoplasms, RNA, Dihydrotestosterone, Testosterone, Age of Onset, Hormone Replacement Therapy, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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