Statin therapy: does sex matter?

Objective: Statins are a class of drugs that competitively bind to the active site of HMG-CoA reductase enzyme, thereby inhibiting the initial steps in cholesterol synthesis. Originally approved for use in lowering serum cholesterol, a risk factor for developing atherosclerosis and coronary heart disease, statins have subsequently been noted to have myriad extrahepatic effects, including potential effects on cognition, diabetes, breast cancer, bone, and muscle. This narrative review assesses the current state of the science regarding the risks and benefits of statin therapy in women to identify areas where additional research is needed. Methods: Basic and clinical studies were identified by searching PubMed with particular attention to inclusion of female animals, women, randomized controlled trials, and sex-specific analyses. Results: Statin therapy is generally recommended to reduce the risk of cardiovascular disease. None of the current clinical guidelines, however, offer sex-specific recommendations for women due to lack of understanding of sex differences and underlying mechanisms of disease processes. In addition, conclusions regarding efficacy of treatments do not consider lipid solubility for the drug, dosing, duration of treatment, interactions with estrogen, or comorbidities. Pleiotropic effects of statins are often derived from secondary analysis of studies with cardiovascular events as primary outcomes. Conclusions: Many of the trials that have established the efficacy and safety of statins were conducted predominantly or entirely in men, with results extrapolated to women. Additional research is needed to guide clinical recommendations specific to women.