ABSTRACT: BACKGROUND:Chronic inflammation is important in the development of benign prostatic hyperplasia (BPH) and certain oral antidiabetic medications have anti-inflammatory properties. The purpose of this study was to determine if use of thiazolidinediones or metformin was associated with a reduced risk of requiring medical or surgical treatment for BPH compared to sulfonylureas among diabetic men. METHODS:We constructed a retrospective cohort of 192,457 male veterans newly prescribed either rosiglitazone, pioglitazone, metformin, or a sulfonylurea. We used Cox proportional hazard regression to assess the association between thiazolidinedione or metformin use and the risk of requiring medical or surgical treatment for BPH compared to sulfonylurea use. New BPH treatment was defined by either a new prescription for a ?-1 blocker or 5?-reductase inhibitors or a surgical procedure indicated for severe BPH. RESULTS:In 259,995 person-years of follow up we identified 14,690 new treatments for BPH. After adjusting for covariates including age, HbA1c, and body mass index, we found no association between rosiglitazone (adjusted hazard ratio [aHR] 1.02, 95% CI 0.86, 1.20), pioglitazone (aHR 0.79, 95% CI 0.45, 1.38), or metformin use (aHR 0.99, 95% CI 0.94, 1.03) and risk of new medical or surgical treatment for BPH compared to sulfonylureas. Analyses ignoring prescriptions for non-selective ?-1 blockers (terazosin, doxazosin, prazosin) from our BPH case definition (n = 11,079), yielded similar results. CONCLUSIONS:In this large cohort, we observed no association between the use of thiazolidinediones or metformin and new medical or surgical treatment for BPH compared to sulfonylureas.