Polycystic ovary syndrome (PCOS) is a major cause of reproductive and metabolic dysfunction in women, but it remains an enigmatic condition whose treatment is necessarily empirical (1). It is the principal cause of menstrual irregularity, anovulatory infertility and the distressing cutaneous manifestations of hirsutism and persistent acne, as well being a significant risk factor for development of type 2 diabetes mellitus. The etiology of the syndrome clearly involves both genetic and environmental factors, but there is still much work to be done in identification of the key genes and getting a clearer understanding of the nature of the interaction between genes and environment. Animal models of PCOS have provided valuable insight into the pathogenesis of the syndrome (2–7), particularly large animals, sheep or rhesus monkeys (3–5, 7), which, as predominantly monoovulatory species, most resemble humans. These animals, exposed in utero to very high concentrations of androgens, develop both reproductive and metabolic abnormalities that resemble clinical PCOS, suggesting that the syndrome arises, at least in part, as a result of androgen programming of fetal and postnatal development (6, 8). They also offer, as illustrated by the article by Padmanabhan et al (23) in this issue of Endocrinology, the prospect of testing therapeutic options that are targeted at reversing, or at least attenuating, during puberty or before, the adverse effects of PCOS and thereby altering the natural progression of the syndrome into adult life. From a clinical viewpoint, it is a constant frustration that management of the reproductive and metabolic sequelae of PCOS is more a matter of controlling symptoms than preventing or attenuating the development of the disorder. PCOS is usually first manifest during adolescence and, indeed, there may even be biochemical clues about susceptibility to development of the syndrome in premenarchal girls (9, 10). So an important question to be answered is: if we can intervene therapeutically to reduce hyperandrogenemia and/or improve insulin sensitivity when symptoms first appear during adolescence, can we reduce the impact of the syndrome on menstrual function, fertility, hirsutism and risk of type 2 diabetes mellitus? This very question was posed in the last millennium by Dan Apter in an article entitled “How possible is the prevention of polycystic ovary syndrome development in adolescent patients with early onset of hyperandrogenism?” (11). He concludes: “Well controlled, long-term follow-up studies are needed on the role of prepubertal hyperandrogenism, hyperinsulinemia, gonadotropins, and ovarian morphological aspects in the development of PCOS, and possibilities of prevention.” Unfortunately, we still lack definitive interventional studies. There is good evidence, from the small number of randomized clinical trials, that diet and lifestyle changes in overweight girls (12, 13), and drugs that improve insulin sensitivity, particularly metformin (14, 15), have a positive effect on both ovarian and metabolic function, which is unsurprising given the results from studies in older women. Antiandrogens alone or in combination with insulin sensitizers or combined oral contraceptives appear beneficial in selected subjects (16–19). And there are tantalizing hints that these therapies may be more effective (in terms of preventing progression of symptoms) in adolescent girls than in later