Polycystic Ovary Syndrome: Genetic determinants of the phenotype

markdownabstract__Abstract__ The polycystic ovary syndrome (PCOS) was first described in 1935 by Stein and Leventhal as an association of amenorrhoea, obesity and a typical, polycystically enlarged, appearance of the ovaries at laparatomy1. Taking into account the absence of advanced imaging techniques and the relatively high risk that was associated with abdominal surgery at that time, it is remarkable that this association was noted, and published, as early as 1935. Perhaps this fact alone serves best to demonstrate the wide impact on population health that is associated with the syndrome that is currently recognised as PCOS. It is the most frequently occurring endocrinopathy among women of reproductive age, with an estimated prevalence of 5-10 % among women of fertile age. The ovulatory disorder that accompanies PCOS is the cause of subfertility and is often the most important reason for affected women to seek medical care. Furthermore, the clinical phenotype of PCOS is characterised by signs of elevated levels of free circulating androgens such as hirsutism, acne and male pattern baldness. However it is important to note that, no matter what diagnostic criteria are used, PCOS constitutes a notoriously heterogeneous phenotype. Due to the absence of a robust aetiologic framework for the pathogenesis of PCOS, physicians are not able to provide a single uniform definition that performs as an accurate diagnostic tool for the diagnosis of PCOS. Therefore, the diagnosis is still based on its description as a clinical phenotype that is characterised by a limited number of typical features (such as oligoovulation, hyperandrogenism and/or polycystic appearance of the ovaries on ultrasound examination)