Metabolic syndrome (MS) is a combination of disorders characterized by alterations in carbohydrate metabolism, obesity, systemic arterial hypertension and dyslipidemia, which increase the risk of developing cardiovascular disease and diabetes. Metabolic disorders affect reproductive function controlled by the hypothalamus and the pituitary. A clinical example of such an interaction is represented by Polycystic ovary syndrome (PCOS) one of the most common female endocrine/reproductive disorders. Despite its pathophysiology remains still unclear, the role of insulin resistance as the main driver has been highlighted in recent years, in addition to genetic and environmental causes. Insulin resistance contributes both to metabolic features and to reproductive features [1,2], underlying many phenotypes de-scribed for PCOS patients. Since women with PCOS share symptoms with the MS, lifestyle changes are the key, first-line treatment strategy for their management [3]. However, compliance of such intervention is often reduced and effects unsatisfactory, thus requiring the addition of insulin-sensitizing drug (ISD). Metformin and thiazolidinediones are the main available ISD. Due to the eventual weight gain and cancer risks of thiazolidinediones, prescription of these drugs has been limited only to diabetic patients [4]. In women with PCOS, treatment with metformin ameliorated the cardio-metabolic profile by improving insulin sensitivity, lowering blood glucose and androgen levels, possibly acting through body weight changes [5–8]. Metformin is more active than oral contraceptives in reducing fasting insulin not increasing triglycerides whereas it is less effective in improving menstrual pattern and correcting hyperandrogenism [9]. Metfor-min is also a reasonable option for those women who cannot use oral contraceptives. The main limitations to metformin use are its gastrointestinal side effects (abdominal discomfort, nausea, and diarrhea) and the need to monitor hepatic and renal function [4]. Hence, patients’ compliance remains an issue as for lifestyle changes.