Stephen Franks

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding). 1 In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only nonhirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism. 1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia. [1] 2][3][4] These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility and menstrual cycle abnormalities, but the factors responsible for failure to select a dominant follicle remain unclear. METHOD: Source is authors' own studies and search of the relevant literature. RESULTS: Arrest of antral follicle growth is associated with an abnormal endocrine environment involving hypersecretion of luteinizing hormone and insulin (and perhaps hyperandrogenism). The net effect is secondary suppression of FSH, which leads to inhibition of maturation of otherwise healthy follicles in the cohort. There is, however, emerging evidence for an intrinsic abnormality of folliculogenesis in PCOS that affects the very earliest, gonadotrophin independent, stages of follicle development. There is an increased density of small pre-antral follicles and an increased proportion of early growing follicles. These abnormalities in anovulatory PCOS are further defined by abnormal granulosa cell proliferation and disparate growth of oocyte and surrounding granulosa cells. This suggests that the normal 'dialogue' between oocyte and granulosa cells in these early growing follicles is altered. There is evidence that abnormal, local (follicle-to-follicle) signalling of anti-Müllerian hormone may play a part in disordered folliculogenesis, but it is plausible that other local regulators that have been implicated in normal and abnormal pre-antral follicle development-such as insulin-like growth factors and sex steroids-have a role in aberrant folliculogenesis in PCOS. CONCLUSIONS: Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.