To test the association between statin use and prostate volume (PV) change over time using data from REDUCE, a 4-year randomized controlled trial testing dutasteride for prostate cancer chemoprevention.We identified men with a baseline negative prostate biopsy from REDUCE who did not undergo prostate surgery or develop prostate cancer over the trial period. Men reported statin use at baseline. PV was determined from transrectal ultrasound performed to guide prostate biopsy at baseline, 2- and 4-years post-randomization. Multivariable generalized estimating equations tested differences in PV change over time by statin use, overall and stratified by treatment arm. We tested for interactions between statins and time in association with PV using the Wald test.Of 4,106 men, 17% used statins at baseline. Baseline PV did not differ by statin use. Relative to non-users, statin users had decreasing PVs over the trial period (p=0.027). Similar patterns were seen in dutasteride and placebo arms, though neither reached statistical significance. Mean estimated PV was modestly but significantly lower in statin users relative to non-users in the dutasteride arm at 2-years (4.5%, p=0.032) and 4-years (4.0%, p=0.033), with similar (3-3.3%) but non-significant effects in the placebo arm.If confirmed, our findings support a role for statins in modestly attenuating PV growth, with a magnitude of effect in line with previously-reported PSA-lowering effects of statins (~4%). Future studies are needed to assess whether this putative role for statins in PV growth could impact lower urinary tract symptom development or progression. This article is protected by copyright. All rights reserved.