Statins in the treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The hyperandrogenemia associated with the syndrome is a result of excessive growth and steroidogenic activity of theca-interstitial tissues in response to various factors, including elevated gonadotropins, hyperinsulinemia, and oxidative stress. PCOS frequently coexists with other cardiovascular risk factors, such as dyslipidemia and systemic inflammation. Statins inhibit the synthesis of mevalonate, the key precursor to cholesterol biosynthesis, and reduce cardiovascular morbidity and mortality. Blockade of mevalonate production may also lead to decreased maturation of insulin receptors, inhibition of steroidogenesis (e.g., via limiting the amount of substrate: cholesterol), and alteration of signal transduction pathways that mediate cellular proliferation. The latter depend upon posttranslational modification of proteins (prenylation), a process mediated by mevalonate derivatives. Statins also have intrinsic antioxidant properties. Given the pleiotropic actions of statins, they are likely not only to improve the dyslipidemia associated with PCOS but may also exert other beneficial metabolic and endocrine effects.