Risk of Prostate Cancer in Men Treated With 5α-Reductase Inhibitors-A Large Population-Based Prospective Study

Background: Studies have shown that 5 alpha-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC. Methods: This is a population-based prospective study on all men age 40 years and older with at least one prostate-specific antigen (PSA) test in Stockholm County from January 2007 until December 2015. Data are derived from the Stockholm PSA and Biopsy Register and Prescribed Drug Register in Sweden, containing data on 5-ARI-use before diagnosis of PC. Cox proportional hazards models were used to estimate the cause-specific hazard ratios of PC for each exposure level relative to men not taking the medication. Results: Of the 333 820 men in the cohort, 23 442 (7.0%) were exposed to 5-ARI at some time during the study period of eight years. Treatment with 5-ARI decreased the risk for overall PC, and the effect was larger with longer time of exposure (0.1 to 2 years: hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.71 to 0.93; 2 to 4 years: HR = 0.39, 95% CI = 0.32 to 0.47; 4 to 6 years: HR = 0.40, 95% CI = 0.31 to 0.52; and 6 to 8 years: HR = 0.31, 95% CI = 0.16 to 0.60). Specifically, 5-ARI decreased the risk for PC with Gleason Scores 6 and 7 but did not statistically significantly affect the long-term risk of being diagnosed with a PC with a Gleason Score of 8 to 10 with up to eight years of treatment. Conclusions: Treatment with 5-ARI for lower urinary tract symptoms is safe with respect to prostate cancer risk.