Abstract

Background: Testosterone supplementation (TS) has dramatically increased in the United States (US). We conducted a study of TS and prostate cancer risk using a large US commercial insurance research database. 

Methods: From the HealthCore Integrated Research Database (HIRDSM), we selected men aged 30 years or greater who were new users of TS during 2007-2015. We selected two male comparison groups: 1) unexposed (matched 10:1); 2) new users of a phosphodiesterase type 5 inhibitor (PDE5i). Incident prostate cancer was defined as diagnosis of prostate cancer within four-weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRRs) and 95% confidence intervals (CI) using doubly robust estimation. Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time. 

Results: The adjusted prostate cancer IRR was 0.77 (95%CI: 0.68, 0.86) when comparing TS with the unexposed group and 0.85 (95%CI: 0.79, 0.91) in comparison with the PDE5i group. Inverse associations between TS and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Amongst TS users, duration of exposure was not associated with prostate cancer. 

Conclusion: In this study, men who received TS did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TS and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biologic effect.