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Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are its common features. The treatment approach focuses on the main aberrations, which characterize the different phenotypes. Areas covered: Management strategies targeting the metabolic phenotype include lifestyle modifications for weight loss and improvement of dietary habits, as well as medication, such as insulin-sensitizers. The treatment of hyperandrogenic phenotype includes cosmetic procedures and the combined oral contraceptives with or without antiandrogens. The therapeutic approach to reproductive phenotype includes diet and lifestyle modifications, clomiphene citrate, and aromatase inhibitors. Alternative treatments include dietary supplements, herbs, resveratrol, myo-inositol, and acupuncture. Expert opinion: New studies have shown that higher anti-Müllerian hormone levels, gut microbiome composition, and plasma metabolomics are new parameters that are related to the most severe phenotypes. The clinical phenotypes can change over the lifespan with weight gain and can coexist in the same individual. Individualized treatment remains the main approach but grouping the phenotypes and following therapeutic recommendations may prove to be also clinically appropriate. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Human, animal, and in vitro studies provide evidence that advanced glycation end-products (AGEs) may contribute to the pathogenesis of polycystic ovary syndrome (PCOS) and its metabolic and reproductive consequences. AGEs are able to induce, via activation of key intracellular signaling pathways, the generation of oxidative stress and proinflammatory cytokines, thus contributing to the adverse health impact of PCOS. This review presents the implications of AGEs in several disease pathophysiologies, including PCOS, as well as the cellular and systemic effects of AGEs on insulin resistance (IR), hyperandrogenemia, endoplasmic reticulum (ER) stress, hypoxia, and ovarian function. The gaps in our knowledge will serve as launching pad for future developments ranging from dietary and lifestyle changes to pharmaceutical interventions aiming at potential applications in women with PCOS. © 2019 Elsevier Ltd

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention. © 2019 European Society of Endocrinology.

Advanced glycation end products accumulate in the ovarian granulosa-cell layer of women with polycystic ovarian syndrome. Taken that the MAPK/ERK-pathway is a key regulator of oocyte maturation and function, consisting the main pathway used by the gonadotrophic hormones (luteinizing hormone, follicle stimulating hormone) to control ovulation, the present study aims to assess advanced glycation end products' interference into luteinizing hormone-and follicle stimulating hormone-signaling via the MAPK/ERK-pathway in the human granulosa KGN cell line. KGN cells were treated with luteinizing hormone or follicle stimulating hormone in the absence or presence of human glycated albumin. The specific activation of the main components of the MAPK/ERK1/2-pathway (namely c-Raf, MEK and ERK1/2) was assessed. Treatment of KGN cells with an MEK1/2-inhibitor or a blocking anti-RAGE-antibody was also performed to shed further light on the mechanism of the involvement of advanced glycation end products in luteinizing hormone and/or follicle stimulating hormone-related signaling pathways. Luteinizing hormone treatment increased p-ERK1/2 levels in human granulosa cells, while the combined treatment of luteinizing hormone and human glycated albumin provoked a decrease of p-ERK1/2 levels. A similar reducing effect was also observed for the upstream molecule phospho-cRaf upon combined treatment, while treatment with an MEK-inhibitor confirmed that the phenomenon is MAPK/ERK-pathway-dependent. Similarly, follicle stimulating hormone treatment increased p-ERK1/2 and p-MEK1/2 levels, while the combined treatment of follicle stimulating hormone and human glycated albumin downregulated their levels. Advanced glycation end products reduce the luteinizing hormone- and follicle stimulating hormone-induced ERK1/2 activation that is critical for granulosa cell mitogenesis and proliferation. Inappropriate activation of ERK1/2 in granulosa cells may block the granulosa cell differentiation pathway and/or impair follicular responses to hormones, potentially leading to ovulation failure that characterizes polycystic ovarian syndrome. © 2017, © 2017 by the Society for Experimental Biology and Medicine.

Objective: The aim of this study was to evaluate the association between thyroid function abnormalities and breast cancer and, in particular, the prognostic markers of breast cancer.. Subjects and methods: Baseline levels of thyrotropin, free triiodothyronine, free thyroxine and thyroid autoantibodies were measured in 97 women with primary breast cancer, 27 women with benign breast disease, and 4 women with atypical ductal hyperplasia. Their baseline levels were compared with those in 48 healthy women with a normal mammography in the last 2 years. Results: There were no significant associations between history of thyroid disease and breast cancer (p = 0.33). The mean baseline levels of triiodothyronine and thyrotropin did not differ significantly between the compared groups. The mean baseline levels of free thyroxine were found to be significantly higher in the breast cancer group, even after adjusting for thyroid replacement therapy. The presence of thyroid antibodies did not differ significantly between the compared groups. In a subgroup analysis, breast cancer cases with thyroid disease and particularly hypothyroidism had a significantly lower incidence of lymph node metastases compared with breast cancer cases without thyroid disease. Conclusions: Our data confirmed the proliferative effect of thyroid hormones on breast cells, which had previously been shown in vitro. Additionally, thyroid disease and particularly hypothyroid function appeared to be associated with a lower incidence of lymph node metastases. Further studies to determine the prognostic role of thyroid hormones in breast cancer are warranted. © AE&M all rights reserved.

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity. © 2017 European Society of Endocrinology Printed in Great Britain.

PCOS is a clinical heterogeneous entity of female androgen excess diagnosed by exclusion of other disorders responsible for androgen excess. The concept of secondary PCOS implies that there is a primary well-defined cause leading to the PCOS phenotype with underlying androgen overproduction, regardless of the origin. In these cases, we presume the term of 'secondary PCOS' could be used. In all these conditions, the potential complete recovery of the hyperandrogenemic state as well as the remission of the PCOS phenotype should follow the removal of the cause. If accepted, these concepts could help clinicians to perform in-depth investigations of the potential factors or disorders responsible for the development of these specific forms of secondary PCOS. Additionally, this could contribute to develop further research on factors and mechanisms involved in the development of the classic and the nonclassic PCOS Phenotypes. © 2016 European Society of Endocrinology Printed in Great Britain.

Endothelial dysfunction involves deregulation of the key extracellular matrix (ECM) enzyme lysyl oxidase (LOX) and the vasoconstrictor protein, endothelin-1 (ET-1), whose gene expression can be modulated by the transcriptional activators nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1). Advanced glycation end products (AGEs) present an aggravating factor of endothelial dysfunction which upon engagement to their receptor RAGE induce upregulation of mitogen-activated protein kinases (MAPKs), leading to NF-κB and AP-1 potentiation. We hypothesized that AGEs could induce NF-κΒ- and AP-1-dependent regulation of LOX and ET-1 expression via the AGE/RAGE/MAPK signaling axis. Western blot, real-time qRT-PCR, FACS analysis and electrophoretic mobility-shift assays were employed in human aortic endothelial cells (HAECs) following treatment with AGE-bovine serum albumin (AGE-BSA) to investigate the signaling pathway towards this hypothesis. Furthermore, immunohistochemical analysis of AGEs, RAGE, LOX and ET-1 expression was conducted in aortic endothelium of a rat experimental model exposed to high- or low-AGE content diet. HAECs exposed to AGE-BSA for various time points exhibited upregulation of LOX and ET-1 mRNA levels in a dose- and time-dependent manner. Exposure of HAECs to AGE-BSA also showed specific elevation of phospho(p)-ERK1/2 and p-JNK levels in a dose- and time-dependent fashion. AGE administration significantly increased NF-κΒ- and AP-1-binding activity to both LOX and ET-1 cognate promoter regions. Moreover, LOX and ET-1 overexpression in rat aortic endothelium upon high-AGE content diet confirmed the functional interrelation of these molecules. Our findings demonstrate that AGEs trigger NF-κΒ- and AP-1-mediated upregulation of LOX and ET-1 via the AGE/RAGE/MAPK signaling cascade in human endothelial cells, thus contributing to distorted endothelial homeostasis by impairing endothelial barrier function, altering ECM biomechanical properties and cell proliferation. © 2015 Springer International Publishing.

Background/Aims: Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (γGT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (p

Granulopoiesis abnormalities have been described in association with thyroid disorders (TD). However, data regarding systematic evaluation of adult neutropenia and concurrent or prior TD are scarce. To investigate the frequency of TD among patients presenting with neutropenia, and the immunophenotypic and immunologic profile of neutropenic patients with concomitant thyroidopathy. Two hundred eighteen consecutive neutropenic patients were prospectively evaluated in our outpatient Hematology Clinic, with a detailed laboratory screen, including thyroid function tests, antineutrophil antibodies, blood lymphocytes immunophenotyping, and detection of T-cell clonality by PCR. Among 218 patients with neutropenia, 95 (43.6%) had TD, 65 chronic immunologic neutropenia, 20 clonal proliferation of T-large granular lymphocytes (T-LGL), 5 autoimmune disorders, and 33 other diagnoses. TD-patients had an increased frequency of recurrent infections compared with other patients (P=0.045). The following correlations were found: negative correlation between FT3 and absolute neutrophil count (ANC) (r 2 =-0.274, P=0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r 2 =-0.16, P=0.045; r 2 =-0.266, P=0.001), and CD4 + counts were inversely correlated to T4 and positively to TSH (r 2 =-0.274, P=0.024; r 2 =0.16, P=0.045). In addition, TD-patients had significantly higher percentages of CD4 + lymphocytes (P=0.003). Among TD-patients, 23.4% had Hashimoto thyroiditis (HT), 4.1%, Graves disease (GD), 8.2% nontoxic multinodular goiter (NTMG), 5% subclinical hypothyroidism, and 2.8% had undergone total thyroidectomy associated with nodules (TTM). Thirteen TD-patients displayed T-LGL. Patients with autoimmune thyroidopathy had an increased frequency of concomitant autoimmune manifestations (P=0.03). Significant differences between the different thyroidopathies included: HT-patients had higher percentages of B-lymphocytes, while the opposite was evident for the TTM-subgroup (P=0.009, 0.02); GD-patients showed an increase of the proportion of NK cells and a decrease in the percentage of TCRγδ+ lymphocytes (P=0.001, 0.045); and NTMG-patients had significantly higher ANC (P=0.004) compared to other thyroidopathies. Antineutrophil antibodies were found in 37.2% of TD-patients tested. Anti-TPO titers were significantly higher in patients with positive antineutrophil antibodies (P=0.04). The frequency of TD among neutropenic patients may be higher than previously reported. The existence of antineutrophil antibodies, as well as the different distribution of lymphocyte subsets among patients with different TD, suggests both humoral and cellular mechanisms in the pathophysiology of thyroid disease-associated neutropenia. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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

Background: Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. Objective: To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging. Design: A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR. Setting: An outpatient clinic was chosen for the study. Participants: A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group. Main outcome and measures: The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated. Results: In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r:-0.266, -0.233, -0.192, P

Objective: To investigate the impact of dietary intervention on Advanced Glycation End products (AGEs) intake on the hormonal and metabolic profile in women with polycystic ovary syndrome (PCOS). Methods: After baseline evaluation, 23 women with PCOS [mean±SD, age: 23.4±5.7 years; body mass index (BMI): 26±5.7 kg/m2] underwent the following consecutive 2-month dietary regimens: a hypocaloric diet with ad-libitum AGEs content (Hypo), an isocaloric diet with high AGEs (HA) and an isocaloric diet with low AGEs (LA). Metabolic, hormonal and oxidative stress status was assessed and AGEs levels were determined in all subjects after the completion of each dietary intervention. Results: Serum levels of AGEs, testosterone, oxidative stress, insulin and HOMA-IR index were significantly increased on the HA compared to the Hypo diet and subsequently decreased on the LA diet (compared to HA) (p

Hyperandrogenemia modifies phenotypic characteristics of women with polycystic ovary syndrome (PCOS). The aim of the present study is to evaluate (a) the prevalence of hyperandrogenemia in PCOS women (Rotterdam criteria) and (b) the impact of either the degree or the type of hyperandrogenemia on phenotype. Anthropometric, clinical, hormonal, metabolic and ultrasound characteristics of 1,218 women with PCOS were analyzed in this cross-sectional study. The prevalence of hyperandrogenemia was 58.8 %. Women with hyperandrogenemia had higher luteinizing hormone (LH), follicle-stimulating hormone (FSH), free androgen index, lower sex-hormone-binding globulin (SHBG) and fasting glucose levels compared to women with normal androgens (p

Objective The clinical phenotype of polycystic ovary syndrome (PCOS) includes reproductive and hormonal aberrations. Visceral adiposity index (VAI) is an indicator which could connect hyperandrogenism and anovulation. The objective was to evaluate the relationship between VAI, menstrual disorders and hormonal, biochemical and ultrasound parameters in women with PCOS. Patients One hundred and ninety-three women with PCOS diagnosed with Rotterdam criteria. Measurements We correlated VAI with metabolic and clinical features of the syndrome and with indices of inflammation and insulin sensitivity. In addition, we classified the patients into four groups according to the severity of menstrual disorders: Group A (n = 42), with severe menstrual disorders, Group B (n = 83), with mild menstrual disorders, Group C (n = 58), without menstrual disorders and Group D (n = 10) with women with sychnominorroia. Results In women with PCOS studied, VAI significantly positively correlated with body weight, fasting glucose, insulin, homeostasis model assessment (HOMA) score, white blood cells, platelets, uric acid, free testosterone, oestradiol, total cholesterol, γ-GT, SGPT. Furthermore, a significant inverse correlation between VAI and SHBG, Matsuda index and menstrual cycles per year was documented. From the comparison of the four groups, PCOS women with menstrual disorders had significantly higher VAI and HOMA indices when compared to PCOS without menstrual disorders. Conclusions Visceral adiposity index is increased in patients with PCOS in concordance with the severity of anovulation, insulin resistance and inflammation. This index could be a very easy and helpful clinical tool in daily practice to predict insulin resistance in women with PCOS. © 2014 John Wiley & Sons Ltd.

Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.

Objective: To compare the effects of oral contraceptives (OCPs) and metformin on atherogenic markers, including serum levels of advanced glycated end products (AGEs) and Creactive protein (CRP), in lean women (Body Mass Index below 25 kg/m2) with polycystic ovary syndrome (PCOS), defined by NIH criteria. Design: Prospective open-label study. Results: One hundred and twenty women with PCOS were treated for 6 months with one of the following treatments: ethinylestradiol plus cyproterone acetate (OCP 1, n=40) or ethinylestradiol plus drospirenone (OCP2, n=40) or metformin (MET, n=40). The three groups were age and BMI-matched (mean age: 22 ± 0.56 yrs in group OCP1; 23.24 ± 0.64 yrs in group OCP2; 21.50 ± 0.53 yrs in group MET; mean BMI 21.80 ± 0.35 kg/m2 in group OCP1; 22.37 ± 0.48 kg/m2 in group OCP2; 23.03 ± 0.67 kg/m2 in group MET). At 6 months serum AGEs were decreased in group OCP1 (P=0.005) and group MET (P=0.001), whereas these were marginally decreased in group OCP2 (P=0.069). Treatment with metformin was associated with a greater percent decrease of AGEs. CRP was decreased with metformin (P

Polycystic ovary syndrome (PCOS) is a heterogeneous spectrum of symptoms lasting throughout the lifecycle. The syndrome combines reproductive as well as metabolic aberrations associated with increased cardiovascular risk. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic diversity of the syndrome. The clinical manifestations and the sequelae of PCOS vary throughout the lifecycle, partly depending on environmental factors which may affect the integral components of the syndrome, namely ovarian steroidogenesis, ovulation and insulin resistance. As the patient grows older, particularly in the postmenopausal period, the cardiovascular risk profile may translate into increased rates of cardiovascular morbidity. © 2014 Informa Healthcare.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes © 2013 Bentham Science Publishers.