Impact of Testosterone Therapy on Prostate Health in Seniors

 Testosterone replacement therapy (TRT) was linked to a lower risk for prostate cancer and a modestly higher risk for benign prostatic hyperplasia in men aged 65 years or older with hypogonadism. The strength of the association varied based on treatment duration, route of administration, and whether an aromatase inhibitor was coadministered.

METHODOLOGY:

• Although the Endocrine Society guidelines recommend TRT for men with testosterone levels ≤ 300 ng/dL in two morning samples, a primary concern is its potential to exacerbate prostate-related conditions such as prostate cancer and benign prostatic hyperplasia.
• To address concerns about potential prostate-related complications associated with TRT, researchers analyzed Medicare enrollment and claims data from 2007 to 2020 for men aged 65 years or older with diagnosed primary or secondary hypogonadism.
• They used propensity score matching to compare TRT users with nonusers based on age at the time of hypogonadism diagnosis; 546,964 and 412,782 men were in prostate cancer analysis and benign prostatic hyperplasia analysis groups, respectively.
• Treatment categorization included the duration of use (short term ≤ 1 year or long term > 1 year), administration route (topical or parenteral), and aromatase inhibitor coadministration.

TAKEAWAY:

• The use of TRT was associated with a 16% reduction in the risk for prostate cancer (hazard ratio [HR], 0.84; 95% CI, 0.82-0.86), with reductions being observed across long-term (15%), short-term (16%), parenteral (12%), and topical (13%) use; TRT plus aromatase inhibitor therapy was not linked to a reduced risk for prostate cancer.
• Analyses that excluded men with high prostate-specific antigen levels or a family history of prostate cancer showed that those on TRT had an 18% lower risk of developing prostate cancer.
• However, the use of TRT showed a 13% increased risk for benign prostatic hyperplasia (HR, 1.13; 95% CI, 1.11-1.14), with a larger increase seen for parenteral vs topical administration (19% vs 12%); the use of TRT was linked to an increased risk for benign prostatic hyperplasia regardless of the use of aromatase inhibitor therapy.
• Long-term use of topical TRT was associated with the smallest increase in the risk for benign prostatic hyperplasia.

IN PRACTICE:

“Despite its proven efficacy in managing hypogonadism, many men remain untreated due to the concern about PCa [prostate cancer] risk. Our findings provide reassuring evidence that may support more informed, individualized clinical decision-making, potentially encouraging reconsideration of TRT among eligible men who have been hesitant to initiate therapy due to fear of PCa or BPH [benign prostatic hyperplasia],” the authors of the study wrote.

SOURCE:

This study was led by Seo Hyon Baik, PhD, Division of Intramural Research, National Library of Medicine, National Institutes of Health in Bethesda, Maryland. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As an observational study, the study cannot establish causality between TRT use and prostatic outcomes. Baseline testosterone levels at hypogonadism diagnosis could not be determined. Medication exposure was inferred from prescription fill records without confirmation of actual dispensation or consumption. The research was limited to Medicare beneficiaries aged 65 years or older, which may restrict generalizability to younger populations. 

DISCLOSURES:

This study was supported by the Division of Intramural Research of the National Library of Medicine, National Institutes of Health. The authors reported having no conflicts of interest.

https://www.medscape.com/viewarticle/impact-testosterone-therapy-prostate-health-seniors-2025a1000qsy