BACKGROUND:Preclinical models have demonstrated that androgen receptor modulation can influence bladder carcinogenesis with an inverse association observed between serum androgen levels and bladder cancer (BC) incidence. It is still unclear whether 5α-reductase inhibitors, by preventing the conversion of testosterone to dihydrotestosterone, have a similar effect. This study aims to evaluate whether dihydrotestosterone-mediated androgen activity has an impact on BC incidence in a cohort of men included in a clinical trial of finasteride vs. placebo with rigorous compliance monitoring. METHODS:A secondary analysis was performed on all patients enrolled in the Medical Therapy for Prostatic Symptoms (MTOPS) Study and included in the biopsy substudy. Men were stratified into groups based on receiving finasteride and the incidence of BC compared between the groups. RESULTS:After exclusions for poor finasteride compliance (n = 338) and missing serum hormone results (n = 9), 2,700 men were eligible for analysis. In total, 0.8% (n = 18) of the cohort was diagnosed with BC during the trial period. There was no difference in the incidence of BC between men who received finasteride and those who did not (0.74% [n = 9] vs. 0.61% [n = 9], P = 0.67). Neither serum testosterone levels, prostate cancer diagnosis nor urinary bother (measured by International Prostate Symptom Score) demonstrated an association with BC diagnosis. These relationships were consistent in the subgroup of men in the biopsy substudy. CONCLUSION:There was no observable relationship between decreased dihydrotestosterone levels and BC diagnosis.