Statins: protectors or pretenders in prostate cancer?

•Clinical studies suggest benefits of statin use in PCa prevention and therapy.•Statins mainly act by reducing circulating and cellular cholesterol.•Statin tissue penetration must be determined when assessing cell-direct actions.•Randomized clinical trials evaluating statin on PCa therapy are ongoing.

The role of statin therapy in prostate cancer (PCa) prevention and treatment is plagued by controversy. This critical review of published clinical series reveals several caveats in earlier studies, which reported no benefit. Recent studies that adjust for confounding factors have demonstrated statin therapy to be associated with PCa prevention and favorable clinical outcomes. Developed as inhibitors of cholesterol synthesis, the expected mechanism of statin action is systemic cholesterol reduction. By lowering circulating cholesterol, statins indirectly reduce cellular cholesterol levels in multiple cell types, impacting on membrane microdomains and steroidogenesis. Although non-cholesterol mechanisms of statin action have been proposed, they are limited by the uncertainties surrounding in vivo tissue statin concentrations.