STUDY QUESTIONWhat is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference?SUMMARY ANSWERInternational evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS.WHAT IS KNOWN ALREADYPrevious guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist.STUDY DESIGN, SIZE, DURATIONInternational evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength.PARTICIPANTS/MATERIALS, SETTING, METHODSGovernance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. In total, 37 societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels.MAIN RESULTS AND THE ROLE OF CHANCEThe evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (ii) reducing unnecessary testing; (iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (iv) emphasizing evidenc...

The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.

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OBJECTIVE-Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation.RESEARCH DESIGN AND METHODS-Oxygen partial pressure (AT pO 2 ) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay.RESULTS-AT pO 2 was lower in overweight/obese subjects than lean subjects (47 Ϯ 10.6 vs. 55 Ϯ 9.1 mmHg); however, this level of pO 2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO 2 was negatively correlated with percent body fat (R ϭ Ϫ0.50, P Ͻ 0.05). Compared with lean subjects, overweight/ obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator-activated receptor ␥1 and higher collagen VI mRNA expression, which correlated with AT pO 2 (P Ͻ 0.05). Of clinical importance, AT pO 2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1␣ secretion (R ϭ Ϫ0.58, R ϭ Ϫ0.79, P Ͻ 0.05), suggesting that lower AT pO 2 could drive AT inflammation in obesity.CONCLUSIONS-Adipose tissue rarefaction might lie upstream of both low AT pO 2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. Diabetes 58:718-725, 2009 B oth insulin resistance and ␤-cell failure are present in individuals with type 2 diabetes. Insulin resistance is closely linked to adiposity with a central or visceral pattern, providing a greater risk of insulin resistance and metabolic dysfunction. Adipose tissue (AT) serves as an endocrine organ secreting a variety of autocrine, paracrine, and endocrine factors that can produce or prevent insulin resistance (1). The failure of AT to adequately proliferate and/or differentiate to sequester lipids away from liver, skeletal muscle, and the pancreatic ␤-cell has been proposed as a precursor to type 2 diabetes, broadening the number of potential mechanisms linking obesity to insulin resistance (2).The increase in body fat in obesity should be accompanied by an increase in vascularization, in order to provide adequate oxygen and nutrients (3). In contrast to expectations, obese mice have lower AT capillary density (rarefaction, also known as capillary drop out) and decreased vascular endothelial growth factor (VEGF), the most potent angiogenic factor (4,5). Consistent with this model, preclinical studies suggest that obese AT is hypoxic (6); however, the hypothesis that AT rarefaction might lead to hypoxia remains untested.In humans, short-term whole-body hypoxia decreases i...

Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences.

THE PENNINGTON CALERIE TEAMOBJECTIVE -The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (S i ) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS-Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction ϩ12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and S i were assessed at baseline and month 6. RESULTS -At baseline, FCS was related to VAT and IHL (P Ͻ 0.05) but not to IMCL. FCS was also the strongest determinant of S i (P Ͻ 0.01). Weight loss at month 6 was 1 Ϯ 1% (control, mean Ϯ SE), 10 Ϯ 1% (CR), 10 Ϯ 1% (CREX), and 14 Ϯ 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P Ͻ 0.01), but IMCL was unchanged. S i was increased at month 6 (P ϭ 0.05) in the CREX (37 Ϯ 18%) and LCD (70 Ϯ 34%) groups (P Ͻ 0.05) and tended to increase in the CR group (40 Ϯ 20%, P ϭ 0.08). Together the improvements in S i were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS.CONCLUSIONS -Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

Objective Stay‐at‐home orders in response to the COVID‐19 pandemic have forced abrupt changes to daily routines. This study assessed lifestyle changes across different BMI classifications in response to the global pandemic. Methods The online survey targeting adults was distributed in April 2020 and collected information on dietary behaviors, physical activity, and mental health. All questions were presented as “before” and “since” the COVID‐19 pandemic. Results In total, 7,753 participants were included. The sample included 32.2% of individuals with normal weight, 32.1% overweight, and 34.0% had obesity. During the pandemic, overall scores for healthy eating increased (p<0.001), due to less eating out and increased cooking ( p <0.001). Sedentary leisure behaviors increased while time spent in physical activity (absolute time and intensity‐adjusted) declined (p<0.001). Anxiety scores increased 8.78±0.21 during the pandemic and the magnitude of increase was significantly greater in people with obesity (p≤0.01). Weight gain was reported in 27.5% of the total sample compared to 33.4% in participants with obesity. Conclusions The COVID‐19 pandemic produced significant health effects, well beyond the virus itself. Government mandates together with fear of contracting the virus have significantly impacted lifestyle behaviors alongside declines in mental health. These deleterious impacts have disproportionally affected individuals with obesity.

The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.