Context: Concerns about potential prostate-related complications associated with testosterone replacement therapy (TRT) often lead hypogonadal men to remain untreated.
Methods: This large-scale retrospective cohort study aimed to address these concerns by analyzing Medicare enrollment and claims data (Parts A/B/C/D) from 2007 to 2020 for men aged ≥65 with diagnosed primary or secondary hypogonadism. Cox regression analysis and 1:1 propensity score matching, both stratified by age group, were employed to evaluate the association between prostate outcomes and TRT use. TRT use was further categorized by treatment duration, administration route, and aromatase inhibitor (AI) coadministration.
Results: Following propensity score matching, the prostate cancer (PCa) and benign prostatic hyperplasia (BPH) risk analyses included 546 964 and 412 782 hypogonadal men, respectively, with comparable baseline characteristics at the time of hypogonadism diagnosis. TRT use was linked to a significant 16% reduction in the hazard of PCa (HR = 0.84; 95% CI: 0.82-0.86), including reductions observed across long-term (15%), short-term (16%), parenteral (12%), and topical (13%) use. Sensitivity analyses excluding individuals with elevated prostate-specific antigen and family history of PCa similarly demonstrated a 18% reduction in the hazard of PCa among TRT users. Conversely, TRT use exhibited a 13% increase in the hazard of BPH (HR = 1.13; 95% CI: 1.11-1.14), with a larger increase for parenteral (19%) vs topical TRT (12%). Notably, long-term topical use was linked to a modest 9% increase.
Conclusion: TRT use was associated with reduction in PCa hazard and modest increase in BPH hazard. These associations varied by treatment duration, route, and AI coadministration. These findings may inform clinical decision-making regarding TRT use in hypogonadal men and support a more individualized approach to care.
Keywords: benign prostatic hyperplasia; hypogonadism; prostate cancer; testosterone replacement therapy.
Published by Oxford University Press on behalf of the Endocrine Society 2025.