The impact of testosterone-replacement therapy (trt) on benign prostatic hyperplasia (bph) incidence and need for interventions in hypogonadal men

Abstract Introduction Investigations on the application of testosterone-replacement therapy (TRT) in hypogonadal men with benign prostatic hyperplasia (BPH) show contrasting results. While some studies reported increased prostate-related events with TRT, recent evidence suggested that TRT can alleviate BPH symptoms in hypogonadal men. Objective Our main objective was to determine the impact of TRT on BPH incidence in a large cohort of hypogonadal men. We also evaluated the relationship between TRT in hypogonadal men and the need for BPH interventions. Methods This retrospective case-control study used the 2011-2020 IBM MarketScan database to identify males above 18 years old with a hypogonadism diagnosis, and determine if they received TRT. We used ICD-9, -10, CPT, HCPCS, and NDC codes to identify diagnoses, interventions, and medications. We excluded individuals who were diagnosed with congenital genetic disorders (e.g. chromosomal abnormalities), hypothalamic-pituitary disorders, or prostatic adenocarcinoma. BPH diagnosis was the primary outcome of this study, and BPH treatment was the secondary outcome. We ran cox proportional hazard (CPH) models from initial hypogonadism diagnosis to BPH occurrence to investigate the effect of TRT on the development of BPH. We also used CPH models from time of BPH diagnosis to first intervention, to evaluate the impact of TRT on BPH interventions. In all models we controlled for age, geographic region, population density, and comorbidities. We included TRT within the last 6 as a time-varying covariate in the models. For BPH occurrence there was non-proportionality in the effect of TRT. Thus, we ran two CPH models for BPH occurrence, one from first hypogonadism diagnosis to 912 days (2.5 years), and one from 2.5 years to the end of enrollment. Results In our total cohort of 882570 hypogonadal men, 157185 (17.8%) were diagnosed with BPH. Hyperlipidemia was the most common comorbidity detected in 84% and 68% of hypogonadal men with and without BPH respectively. For the first 2.5 years after hypogonadism diagnosis, there was no significant difference for development of BPH between patients on TRT and those who were not on TRT (HR 1.00, 95%CI 0.98-1.01, p=0.66). However, from 2.5 years onward, men who were on TRT had a 32% greater chance for development of BPH (HR 1.32, 95%CI 1.28-1.36, p<0.001). Hypogonadal men with BPH who received TRT showed no significant difference for BPH interventions compared to those who were not on TRT (HR 0.95, 95%CI 0.89-1, p=0.08). Conclusions In the long term, TRT can increase the risk of development of BPH in hypogonadal men. On the other hand, TRT in hypogonadal men with BPH does not change the need for BPH interventions. Our findings indicate that TRT should be used with caution in hypogonadal men who are at risk of developing BPH but further work is needed to clarify this relationship. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Educational/Research grant: Acerus, Coloplast, Endo, Boston Scientific; Consultant: Turtle Health; Hold equity: StreamDx, FirmTech, Maximus.