Impact of bariatric surgery on anthropometric, metabolic, and reproductive outcomes in polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females. Modest weight loss improves reproductive and metabolic PCOS features. While lifestyle modifications and pharmacotherapies remain first-line weight loss strategies, bariatric surgery is emerging as a potentially effective treatment. We performed a systematic review and meta-analysis of published literature to examine the impact of bariatric surgery in PCOS to inform the 2023 International PCOS Evidence-based Guidelines. Electronic databases were searched for observational studies and trials comparing pharmacologic or lifestyle treatments to bariatric surgery in women with PCOS or bariatric surgery in women with or without PCOS. Anthropometric, reproductive, hormonal, and metabolic outcomes were included and, where possible, meta-analyzed using random-effects models. Risk of bias and evidence quality were assessed. Ten studies were included involving 432 women with and 590 women without PCOS. Comparisons between bariatric surgery and pharmacologic or lifestyle treatments were only reported in one study each, and most reproductive outcomes were limited to a single study; therefore, meta-analyses could not be performed. Meta-analysis found that women with PCOS experience similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared to those without PCOS. Existing research is limited and of low quality with high risk of bias, especially in comparison to existing PCOS treatments and with respect to reproductive outcomes including pregnancy, highlighting the need for additional studies to inform clinical recommendations.

Anti-obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 international evidence-based guideline.

This systematic review and meta-analysis evaluated the efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic ovary syndrome (PCOS) to inform the 2023 update of the International Evidence-based Guideline on PCOS. We searched Medline, EMBASE, PsycInfo, and CINAHL until July 2022 with a 10-year limit to focus on newer agents. Eleven trials (545 and 451 participants in intervention and control arms respectively, 12 comparisons) were included. On descriptive analyses, most agents improved anthropometric outcomes; liraglutide, semaglutide and orlistat appeared superior to placebo for anthropometric outcomes. Meta-analyses were possible for two comparisons (exenatide vs. metformin and orlistat + combined oral contraceptive pill [COCP] vs. COCP alone). On meta-analysis, no differences were identified between exenatide versus metformin for anthropometric, biochemical hyperandrogenism, and metabolic outcomes, other than lower fasting blood glucose more with metformin than exenatide (MD: 0.10 mmol/L, CI 0.02-0.17, I2 = 18%, 2 trials). Orlistat + COCP did not improve metabolic outcomes compared with COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I2 = 67%, 2 trials). Published data examining the effects of anti-obesity agents in women with PCOS are very limited. The role of these agents in PCOS should be a high priority for future research.

Use of anti-Müllerian hormone for understanding ovulatory dysfunction in polycystic ovarian syndrome.

PURPOSE OF REVIEW: The aim of this review is to understand how anti-Müllerian hormone (AMH) contributes to ovulatory dysfunction in polycystic ovarian syndrome (PCOS). RECENT FINDINGS: In the last few years, new findings have emerged on AMH and its role on the central nervous system causing ovulatory dysfunction. SUMMARY: Anovulation is a prominent feature of PCOS. Women with anovulatory PCOS have higher AMH levels than in ovulatory PCOS. Higher levels of AMH may contribute to the pathophysiology of PCOS through central and peripheral actions. Once universal standardization is achieved to measure serum AMH, the benefits would be significant in diagnosing women with PCOS.

The impact of ageing and menopause in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long-term health in ageing women. In this review, we aimed to give an updated overview regarding the long-term health outcomes of PCOS and their clinical implications in peri- and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long-term cohort studies. Large, prospective studies on community-based and well-phenotyped PCOS cohorts with extended follow-up into late menopause are needed to confirm these findings.

The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.

The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.

Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review.

This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute. saPCOS had higher androgen and lower sex hormone-binding globulin (SHBG) concentrations, mePCOS had higher DHEAS concentrations, and hPCOS and Black women with PCOS (bPCOS) had lower SHBG and DHEAS measures than wPCOS. Menstrual disturbances were more frequent in eaPCOS. Both saPCOS and eaPCOS had lower body mass index with increased central adiposity. hPCOS and bPCOS were more obese. saPCOS, mePCOS, hPCOS and bPCOS had a higher prevalence of insulin resistance than wPCOS. bPCOS had a better lipid profile but higher blood pressure and cardiovascular risk. Indigenous Australian women with PCOS were more obese and more insulin resistant with higher androgen concentrations. The clinical phenotype of PCOS therefore shows a wide variation depending on ethnicity.

Obesity and physical exercise.

Obesity represents a major health problem worldwide and is associated with increased prevalence of numerous health-related conditions, including diabetes, hypertension, cardiovascular disease, some forms of cancer and musculoskeletal disorders, among others. Studies that have examined the impact of physical exercise combined with energy restriction diets on weight have shown greater weight loss compared to interventions of exercise-only. Accordingly, the most effective approach to achieve significant weight loss includes a combination of diet, exercise and behavioral strategies. Current guidelines recommend participating in at least 150 minutes of moderate-intensity or 75 minutes of vigorous intensity aerobic exercise weekly, and resistance/muscle strengthening training, involving all major muscle groups at least twice a week. For patients seeking to maintain weight loss, high levels of exercise (225-420 min/week of moderate intensity exercise) have been associated with improved weight maintenance compared to lower levels (<150 min/week). Weight loss has been associated with improvements in prevalence and severity of several obesity associated comorbidities such as insulin resistance, inflammation, dyslipidemia, hypertension, metabolic syndrome, diabetes, pulmonary disease and cardiovascular disease. This review summarized the current knowledge regarding the role of exercise in prevention of weight gain, weight loss and maintenance of weight loss in obese individuals, also outlining the data on effects of exercise on complications of obesity and highlighting areas for future research.

Characterization of gut microbiota in polycystic ovary syndrome: Findings from a lean population.

BACKGROUND: Limited available animal and human data suggest an association between dysbiosis of gut microbiota and PCOS. We aimed to determine whether gut microbiota in lean women with PCOS shows any alterations compared to healthy women. MATERIALS AND METHODS: Twenty-four lean patients with PCOS phenotype A according to the Rotterdam 2003 diagnostic criteria and 22 BMI-matched healthy women were included in this study. Anthropometric, hormonal and biochemical measurements were carried out in all participants. 16S rRNA gene V3-V4 region amplicon sequencing was performed on stool samples. Preprocessing of the raw data was performed using QIIME, and both QIIME and R packages were used for microbiome analysis. RESULTS: Bacterial richness and diversity did not show a significant difference between patients and controls. Beta diversity was similar between the groups. However, Erysipelotrichaceae, Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, Planococcaceae, Gemmules and Bacillales were significantly abundant in PCOS group according to LEfSe analysis. Clostridium cluster XVII showed increased abundance in patient group, while Clostridium sensustricto and Roseburia were decreased compared to controls. Random forest prediction analysis revealed Clostridium cluster XIVb as the most discriminative feature of patient group and Roseburia for healthy controls. Testosterone and androstenedione were negatively correlated with alpha and phylogenetic diversity. CONCLUSIONS: Our results suggest that gut microbiome of lean PCOS patients with full phenotype shows compositional alterations with similar bacterial richness and diversity compared to controls and that hyperandrogenism is associated with dysbiosis.

Tissue fat quantification by magnetic resonance imaging: proton density fat fraction in polycystic ovary syndrome.

RESEARCH QUESTION: What are the potential differences between lean women with and without polycystic ovary syndrome (PCOS) in fat content in liver, vertebrae, paraspinal muscles, pancreas, subcutaneous (SCAT) and visceral adipose tissue (VAT)? Magnetic resonance imaging proton density fat fraction (PDFF) was used to establish these differences. This is a novel, non-invasive, operator-independent method with comparable diagnostic sensitivity and specificity to histologic examination for fatty liver disease, and strong correlation with muscle strength in neuromuscular studies. DESIGN: Twenty lean women with PCOS (mean age 23.9 ± 2.3; body mass index [BMI] 22.4 ± 2.0) and 20 age- and BMI-matched healthy women (mean age 24.9 ± 1.5; BMI 21.5 ± 1.9) were enrolled in this cross-sectional study. Anthropometric, biochemical and hormonal evaluations along with magnetic resonance imaging proton density fat fraction were carried out. RESULTS: PDFF% measurements of liver, SCAT and VAT were higher in the PCOS group, indicating increased fat content in these areas in lean women with PCOS compared with controls (P = 0.045, 0.030 and 0.037, respectively). In contrast, PDFF% values of vertebrae and paraspinal muscles in the PCOS group were lower than controls (P = 0.038 and 0.05, respectively). Pancreatic PDFF% measurements were similar between the groups. In the PCOS group, PDFF% of VAT was positively correlated with free androgen index (r = 0.69, P = 0.002). CONCLUSIONS: PDFF% measurement, an MRI-based novel biomarker, reveals increased fat in liver, SCAT and VAT, and decreased fat in vertebral bones and paraspinal muscles of lean women with PCOS.

Recommendations for epidemiologic and phenotypic research in polycystic ovary syndrome: an androgen excess and PCOS society resource.

STUDY QUESTION: What are the best practices for undertaking epidemiologic and phenotypic studies in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Best practices for the undertaking of epidemiologic and phenotypic studies in PCOS are outlined. WHAT IS KNOWN ALREADY: Currently methodologies used for studies of PCOS epidemiology and phenotypes vary widely, and the comparability of studies is low, reducing the ability to harmonize studies. STUDY DESIGN, SIZE, DURATION: The Androgen Excess and PCOS (AE-PCOS) Society established a Task Force to draft a research resource for epidemiologic and phenotypic studies in PCOS, with the aim of providing guidelines on study design and execution, insights into the limitations and alternatives and protocols to be used, taking into consideration a global perspective. PARTICIPANTS/MATERIALS, SETTING, METHODS: A targeted review of the literature was carried out as necessary. MAIN RESULTS AND THE ROLE OF CHANCE: High level recommendations include the following: (i) Before initiating the study, a number of critical factors should be addressed including selecting the population and diagnostic criteria (which should ideally align with the recommendations of the International Guidelines), the type of observational study to be undertaken and the primary and secondary endpoint(s) of the study.(ii) To assess the 'natural' or true phenotype and epidemiology of PCOS, the least medically biased, broadest and most generalizable population, and the broadest definition of PCOS, should be used.(iii) Four PCOS phenotypes (Phenotypes A through D), based on the presence or absence of three general features (oligo-anovulation, hyperandrogenism and polycystic ovarian morphology), should be ascertained.(iv) In epidemiologic and phenotypic studies, the detection of PCOS rests on the accuracy and sensitivity of the methods used for assessing the individual features of the disorder, and how 'normal' is defined.(v) Although an assessment algorithm that minimizes the use of certain measures (e.g. androgen levels and/or ovarian ultrasonography) can be devised, when possible it is preferable to uniformly assess all subjects for all parameters of interest.(vi) The inclusion of subjects in epidemiologic studies who do not appear to have PCOS (i.e. 'non-PCOS') will provide the necessary cohort to establish population-specific normative ranges for the various features of PCOS. (vii) Epidemiologic studies of PCOS in unselected populations will yield relatively limited numbers of PCOS subjects available for genetic study; alternatively, large population-based epidemiologic studies of PCOS will potentially generate large numbers of unaffected individuals that may serve as genetic controls. (viii) Epidemiologic studies of PCOS will benefit from a clear governance structure and should begin by informing, educating and engaging both the formal and informal leaders of the populations targeted for study. (ix) In designing their study investigators should, in advance, establish statistical power and recognize, manage and account for inherent biases. (x) Subjects suspected of having PCOS but who do not/cannot complete their evaluation (i.e. have 'possible PCOS') can be included by imputation, assigning them a 'diagnostic weight' based on those subjects of similar clinical phenotype that have completed the study. (xi) In obtaining, storing and retrieving subject data, subjects should be assessed consecutively using a uniform data collection form; providing as complete and in depth data as possible. (xii) Maintenance of both paper and electronic medical records should focus on ensuring data quality, accuracy and institutional ethical compliance, and familiarity with country-dependent laws, including biobanking-specific laws, tissue laws and research laws. (xiii) In obtaining and biobanking study samples, these should be ideally collected at the time of the first assessment. (xiv) Access to stored data sets should ideally be granted to other bona fide researchers conducting research in the public interest. (xv) SOPs detailing the exact method of each of the activities for handling the data and the samples are necessary to ensure that all methods are performed uniformly. (xvi) Epidemiologic studies of PCOS must be resourced adequately. LIMITATIONS, REASONS FOR CAUTION: As with all reports involving expert interpretation of experiential and published data, inherent individual biases are possible. This risk is minimized in the present study by including experts from varying fields of study, aligning with recent international evidence-based guidelines and obtaining consensus approval of the recommendations from the Task Force and the board of the AE-PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines should encourage investigators worldwide to undertake much needed epidemiologic studies of PCOS, increasing the validity, integrity and comparability of the data. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. R.A. serves as consultant for Medtronic, Spruce Biosciences and Ansh Labs; has received research funding from Ferring Pharmaceuticals; and is on the advisory board of Martin Imaging; R.L. has received research funding from MSD Pharmaceuticals; J.L. has received fees and/or grant support from the Dutch Heart Association, The Netherlands Organisation for Health Research and Development (ZonMw), Ferring Pharmaceuticals, Danone, Euroscreen/Ogeda and Titus Health Care; H.T. receives grant funding from the National Health and Medical Research Council; K.K., L.M.-P., S.S.M. and B.O.Y. have no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The association of cardiorespiratory fitness, body mass index, and age with testosterone levels at screening of healthy men undergoing preventive medical examinations: The Cooper Center Longitudinal Study.

BACKGROUND: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging. METHODS: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness. FINDINGS: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age. INTERPRETATION: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.

Androgen Excess- Polycystic Ovary Syndrome Society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome.

OBJECTIVE: To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with polycystic ovary syndrome (PCOS) and review prevalence based on phenotypes and ethnicity, changes over time, etiology, and impact of treatment. DESIGN: Systematic reviews and preparation of position statement. SETTING: Not applicable. PATIENT(S): Women with PCOS and controls screened using validated tools. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Depressive symptoms, anxiety symptoms, disordered eating, and HRQoL scores. RESULT(S): Several studies demonstrate that women with PCOS have an increased prevalence of higher depression and anxiety scores and higher odds of moderate and severe depressive and anxiety symptoms compared with controls. Obesity, hyperandrogenism, and fertility have a weak association with these symptoms. HRQoL scores are consistently reduced in PCOS, with infertility and weight concerns having the most significant impact. Some studies suggest an increased prevalence of disordered eating in women with PCOS compared with controls. The few studies that have evaluated the impact of PCOS-related treatments (lifestyle interventions and pharmacotherapy) show no detrimental effect or some improvement in depressive and anxiety symptoms and HRQoL scores. CONCLUSION(S): In women with PCOS, screening for depressive and anxiety symptoms should be offered at the time of diagnosis and screening for disordered eating should be considered. Further research is required across PCOS phenotypes, in longitudinal cohorts and on impact of therapy on depressive and anxiety syptoms, HRQOL, and disordered eating.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.

Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women and is characterized by two of the following three features: oligoovulation or anovulation, clinical and/or biochemical signs of hyperandrogenism, or polycystic ovaries. SUMMARY: It has been demonstrated that PCOS includes a complex number of systemic symptoms in addition to symptoms related to the reproductive apparatus. It has been associated with obesity, metabolic syndrome, type 2 diabetes and an increased risk of cardiovascular disease. Several clinical and basic studies have investigated the link between PCOS and the cardiovascular disease risk, which seems to be due to blunted lipid/glucose metabolism, hypertension, and systemic inflammatory and coagulation disorders. Therefore, the current manuscript aims to review the main findings on PCOS and obesity/obesity-related disease (glucose derangements and cardiovascular disease risk factors). KEY MESSAGE: Although there are no long-term data on the morbidity and mortality for cardiovascular disease in PCOS, it is advisable to perform a careful metabolic and cardiovascular assessment in women with PCOS in order to tailor the most suitable strategy to prevent cardiovascular disease.

Polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.

Gut-Brain Axis and Metabolism in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder, often accompanied and complicated by insulin resistance, glucose intolerance and obesity. Gut, brain and metabolism are highly related with each other in obesity and diabetes as well as in PCOS. Central nervous system regulates food intake through complex interactions of homeostatic and hedonic systems while gastrointestinal system contributes to food intake and metabolism via orexigenic and anorexigenic gastrointestinal hormones. Ghrelin is the only circulating orexigenic hormone whereas anorexigenic peptides include glucagon like peptide-1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY) and cholecystokinin (CCK). Compared to healthy women, patients with PCOS show decreased or unaltered fasting ghrelin levels, along with decreased or unaltered postprandial suppression of this hormone. GLP-1, PYY and CCK show unaltered or decreased levels both in fasting and postprandial states in PCOS whereas fasting levels of another gut hormone, GIP is either unaltered or increased. Dietary interventions associated with weight loss or short term oral contraceptive use in PCOS do not alter fasting or postprandial levels of these hormones. However use of metformin is associated with an increase in ghrelin, PYY, GLP-1 and GIP in women with PCOS. GLP-1 agonists and bariatric surgery, both having a significant impact on gut-brain axis, appear to be effective therapeutic options in obese women with PCOS. Finally, alterations in gut microbiota and possible interactions with gut-brain axis in PCOS is a topic of interest. Understanding the relationship between PCOS and homeostatic and hedonic systems, gastrointestinal hormones, and gut microbiota as well as potential effects of different therapeutic interventions on these systems will provide further understanding and novel treatment opportunities for this syndrome.

Approach to the patient: contraception in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder. Patients with PCOS present with clinical signs of androgen excess (ie, hirsutism and acne), menstrual irregularities, and infertility. Combined oral contraceptive (OC) pills are the first-line medical therapy for the long-term management of PCOS. Containing a combination of estrogen and progestin, OCs restore regular menses, improve androgen excess, and provide effective contraception and protection from endometrial cancer. The benefits of hormonal contraception outweigh the risks in the vast majority of women with PCOS. However, concerns have been raised about potential adverse cardiovascular and metabolic effects of OCs. Currently available evidence indicates an increased relative risk of venous thrombosis associated with OCs varying among different formulations. Arterial thrombosis risk attributable to OCs does not appear to be significantly increased in young nonsmoking women. OC use might be associated with increased risk of diabetes in morbidly obese women with PCOS with severe insulin resistance. A tailored clinical approach to oral contraception in women with PCOS requires individualized risk stratification and management by determination of each PCOS patient's personal cardiometabolic risk profile at baseline and during follow-up. Before prescribing an OC, clinicians should document individual risk factors including age, smoking, obesity, any degree of glucose intolerance including prediabetes and diabetes, hypertension, dyslipidemia, thrombophilia, and personal or family history of a venous thromboembolic event.

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 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.