Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality

Importance Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality. Objective To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality. Data Sources A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases. Study Selection Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies. Data Extraction and Synthesis This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022. Main Outcomes and Measures The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline. Results Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen–adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08). Conclusions and Relevance This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.