Evanthia Diamanti-Kandarakis

The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report.

OBJECTIVE To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research. DESIGN Literature review and expert consensus. SETTING Professional society. PATIENTS None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. RESULT(S) The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence. CONCLUSION(S) Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.

Assessment of Cardiovascular Risk and Prevention of Cardiovascular Disease in Women with the Polycystic Ovary Syndrome: A Consensus Statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society

OBJECTIVE Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. PARTICIPANTS An expert panel in PCOS and CVD reviewed literature and presented recommendations. EVIDENCE Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. CONSENSUS PROCESS Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. CONCLUSIONS Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.

Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications

Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulins metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait.

Endocrine Disruptors and Polycystic Ovary Syndrome (PCOS): Elevated Serum Levels of Bisphenol A in Women with PCOS

CONTEXT Bisphenol A (BPA) is a widespread industrial compound used in the synthesis of polycarbonate plastics. In experimental animals, neonatal exposure to BPA results in a polycystic ovary-like syndrome (PCOS) in adulthood. A bidirectional interaction between androgens and BPA levels has been disclosed. OBJECTIVE To determine BPA levels in PCOS women as well as the association between BPA and hormonal/metabolic parameters compared to a control group. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 71 PCOS (National Institutes of Health criteria) and 100 normal women, age- and body mass index-matched, in a University hospital setting. MAIN OUTCOME MEASURES Anthropometric, hormonal, metabolic parameters and BPA blood levels were determined. Patients (PCOS) and controls (C) were further subdivided according to body mass index into lean and overweight subgroups, respectively. RESULTS BPA levels were significantly higher in the total PCOS group compared with the controls (1.05±0.56 vs. 0.72±0.37 ng/ml, P < 0.001). PCOS women, lean (PCOS-L) and overweight (PCOS-OW), had higher BPA levels compared to the corresponding control group lean (C-L) and overweight (C-OW): (PCOS-L = 1.13±0.63 vs. C-L = 0.70±0.36, P < 0.001) (PCOS-OW = 0.96 ± 0.46 vs. C-OW = 0.72 ± 0.39, P < 0.05). A significant association of testosterone (r = 0.192, P < 0.05) and androstenedione (r = 0.257, P < 0.05) with BPA was observed. Multiple regression analysis for BPA showed significant correlation with the existence of PCOS (r = 0.497, P < 0.05). BPA was also positively correlated with insulin resistance (Matsuda index) in the PCOS group (r = 0.273, P < 0.05). CONCLUSIONS Higher BPA levels in PCOS women compared to controls and a statistically significant positive association between androgens and BPA point to a potential role of this endocrine disruptor in PCOS pathophysiology.

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.

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 patients 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.

Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications.

Polycystic ovarian syndrome (PCOS) is universally recognised as the commonest endocrinopathy of women. The definition and the aetiological hypotheses of PCOS are continuously evolving to accommodate expanding knowledge on the syndrome, which is now known to be more complex than purely a reproductive disorder. Increased androgen synthesis, disrupted folliculogenesis and insulin resistance lie at the pathophysiological core of PCOS. An intriguing concept involves the perpetuation of a vicious circle with endocrine/reproductive and metabolic components. An unfavourable metabolic environment may unmask genetic traits of ovarian dysfunction, and the unfolding endocrine derangement could further aggravate the metabolic disarray. This article reviews the molecular mechanisms known to underlie the ovarian and metabolic abnormalities characterising PCOS. The putative interdependence between reproductive and metabolic aspects of PCOS, and therapeutic implications for the management of PCOS, are also discussed.

Pathophysiology and types of dyslipidemia in PCOS

Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects women of reproductive age. PCOS shares components with the metabolic syndrome and has broad health implications. Lipid abnormalities, including elevated low-density lipoprotein (LDL), triglyceride levels and decreased high-density lipoprotein (HDL), are often found in women with PCOS. It is clear that obesity, insulin resistance and hyperandrogenism coexist in PCOS, and have independent and interactive effects on dyslipidemia, although the mechanisms of these interactions remain elusive. Here, we review the types and pathophysiology of dyslipidemia associated with PCOS and its related conditions.

Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6-6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women. Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformins targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformins cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.

Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome

objective  Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end‐products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes.

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

Background  Nonenzymatic advanced glycation and oxidation end‐products, advanced glycation end‐products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress.