Polycystic ovary syndrome (PCOS) is a common disorder often emerging post-menarche with anovulatory oligomenorrhea. and signs of androgen excess. Associated hyperinsulinemic insulin resistance, dyslipidemia, increased central fat and dysadipocytokinemia herald long-term disease risk. Longitudinal studies in girls with either precocious pubarche, low birthweight, or both of these, suggest that the pathophysiological basis of non-obese PCOS is established well before the onset of puberty, and that hyperinsulinemic insulin resistance is a key factor. Intervention studies in adolescents and young women with PCOS have shown that a combined low-dose therapy with an insulin-sensitizer and an androgen-receptor blocker attenuates the spectrum of endocrine-metabolic and body composition anomalies. These benefits are maintained, if a fourth-generation oral contraceptive (OC) is added, as a safety measure. In two prevention studies conducted in young girls at risk, metformin was used in monotherapy, and this approach proved effective and safe in reversing the endocrine-metabolic disturbances associated to PCOS, and thus, presumably, in delaying the development of overt disease and long-term risks.