Growth hormone as a potential mediator of aerobic exercise-induced reduction in visceral adipose tissue

Obesity remains one of the leading causes of death worldwide and is a well-known risk factor for a myriad of non-communicable diseases including diabetes, cardiovascular disease, and a variety of cancers (Wolf and Colditz, 1998; Frühbeck et al., 2013). While the relationship between obesity and cardiometabolic risk is well-established, the location of adipose tissue, particularly in the abdominal region, is considered a greater predictor of metabolic dysfunction than total fat mass (Kahn et al., 2006). Central obesity, characterized by the excess accumulation of adipose tissue in the abdominal region, is strongly and independently correlated with metabolic syndrome and is assessed clinically through the measurement of waist circumference (Shen et al., 2006). Central adiposity can be further subcategorized into abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (Snel et al., 2012). While the relationship between SAT and cardiometabolic risk remains equivocal, VAT has been established as a unique pathogenic fat depot. VAT acts as an endocrine organ by secreting adipocytokines and other vasoactive substances (Kanaya et al., 2004) and is associated with cardiometabolic risk independent of body mass index (BMI) or total body adiposity (Fox et al., 2007; Pak et al., 2016). Consequently, it is important to identify new, as well as further develop existing therapies to improve the management of obesity

Do vigorous-intensity and moderate-intensity physical activities reduce mortality to the same extent? : a systematic review and meta-analysis

Objective: To examine whether vigorous-intensity physical activity confers additional reductions on all-cause and cause-specific mortality compared with moderate-intensity physical activity. Design: A systematic review (registered in PROSPERO CRD42019138995) and meta-analysis. Data sources: Three electronic databases up to April 14 2020. Eligibility criteria: Inclusion criteria were prospective studies that contained information about (1) moderate-intensity (3–5.9 metabolic equivalent tasks (METs)) and vigorous-intensity (≥6 METs) physical activities and (2) all-cause and/or cause-specific mortality. Exclusion criteria were prospective studies that (1) exclusively recruited diseased patients (eg, hypertensive patients and diabetics) or (2) did not account for total physical activity in their multivariable models (3) or did not adjust or exclude individuals with comorbidities at baseline or (4) used physically inactive participants as reference group. Results: Five studies (seven cohorts using sex-specific results) were pooled into a meta-analysis. For all-cause mortality and controlling by total physical activity, vigorous-intensity physical activity (vs moderate) was not associated with a larger reduction in mortality (HR 0.95, 95% CI 0.83 to 1.09). After the exclusion of one study judged with critical risk of bias (Risk Of Bias in Non randomized Studies, ROBINS tool) from meta-analysis, results remained similar (HR 0.98, 95% CI 0.85 to 1.12). Due to the limited number of studies, meta-analyses for cancer and cardiovascular mortality were not performed. Conclusions: Prospective studies suggest that, for the same total physical activity, both vigorous-intensity and moderate-intensity physical activities reduce all-cause mortality to the same extent. However, absence of evidence must not be interpreted as evidence of absence due to the existing methodological flaws in the literature

Effect of aerobic exercise on waist circumference in adults with overweight or obesity : a systematic review and meta-analysis

Excess visceral adiposity contributes to elevated cardiometabolic risk, and waist circumference is commonly used as a surrogate measure of visceral adipose tissue. Although regular aerobic exercise is known to improve abdominal obesity, its effect on waist circumference is unclear. A systematic review and meta-analysis was performed to determine (1) the effect of aerobic exercise on waist circumference in adults with overweight or obesity; (2) the association between any change in waist circumference and change in visceral adipose tissue and/or bodyweight with aerobic exercise interventions; and (3) if reductions in waist circumference with exercise are moderated by clinical characteristics or components of aerobic exercise prescription. Twenty-five randomized controlled trials (1686 participants) were included. Regular aerobic exercise significantly reduced waist circumference by 3.2 cm (95% confidence interval [CI] −3.86, −2.51, p ≤ 0.001) versus control. Change in waist circumference was associated with change in visceral adipose tissue (β = 4.02; 95% CI 1.37, 6.66, p = 0.004), and vigorous intensity produced superior reduction (−4.2 cm, 95% CI −4.99, −3.42, p < 0.0001) in waist circumference compared with moderate intensity (−2.50 cm, 95% CI −3.22, −1.79, p = 0.058). These findings suggest regular aerobic exercise results in modest reductions in waist circumference and associated visceral adipose tissue and that higher intensity exercise may offer superior benefit to moderate intensity

The association between cardiorespiratory fitness, liver fat and insulin resistance in adults with or without type 2 diabetes : a cross-sectional analysis

Background: Exercise-induced improvements in cardiorespiratory fitness (CRF) often coincide with improvements in insulin sensitivity and reductions in liver fat content. However, there are limited data concerning the relationship between CRF and liver fat content in adults with varying degrees of metabolic dysfunction. Methods: The aim of this study was to examine the association between CRF, liver fat content, and insulin resistance in inactive adults with obesity and with or without type 2 diabetes (T2D), via cross-sectional analysis. CRF was determined via a graded exercise test. Liver fat content was assessed via proton magnetic resonance spectroscopy and insulin resistance was assessed via homeostatic model of insulin resistance (HOMA-IR). A partial correlation analysis, controlling for age and gender, was performed to determine the association between CRF, demographic, cardiometabolic, and anthropometric variables. Independent t tests were performed to compare cardiometabolic outcomes between participants with T2D and participants without T2D. Results: Seventy-two adults (46% male) with a mean age of 49.28 ± 10.8 years, BMI of 34.69 ± 4.87 kg/m2 , liver fat content of 8.37 ± 6.90%, HOMA-IR of 3.07 ± 2.33 and CRF of 21.52 ± 3.77 mL/kg/min participated in this study. CRF was inversely associated with liver fat content (r = − 0.28, p = 0.019) and HOMA-IR (r = − 0.40, p < 0.001). Participants with T2D had significantly higher liver fat content (+ 3.66%, p = 0.024) and HOMA-IR (+ 2.44, p < 0.001) than participants without T2D. Participants with T2D tended to have lower CRF than participants without T2D (− 1.5 ml/kg/min, p = 0.094). Conclusion: CRF was inversely associated with liver fat content and insulin resistance. Participants with T2D had lower CRF than those without T2D, however, the difference was not statistically significant. Further longitudinal studies are required to elucidate the relationship between CRF and the progression of obesity-related diseases such as T2D. Registration: ACTRN12614001220651 (retrospectively registered on the 19th November 2014) and ACTRN12614000723684 (prospectively registered on the 8th July 2014)

Educational differences in diabetes mortality among hispanics in the United States : an epidemiological analysis of vital statistics data (1989–2018)

Background: Diabetes accounted for approximately 10% of all-cause mortality among those 20–79 years of age worldwide in 2019. In 1986–1989, Hispanics in the United States of America (USA) represented 6.9% of the national population with diabetes, and this proportion increased to 15.1% in 2010–2014. Recently published findings demonstrated the impact of attained education on amenable mortality attributable to diabetes among Non-Hispanic Whites (NHWs) and Non-Hispanic Blacks (HNBs). Previous cohort studies have shown that low education is also a detrimental factor for diabetes mortality among the Hispanic population in the USA. However, the long-term impact of low education on diabetes mortality among Hispanics in the USA is yet to be determined. Aims and methods: The aim of this study was to measure the impact of achieving a 12th-grade education on amenable mortality due to diabetes among Hispanics in the USA from 1989 to 2018. We used a time-series designed to analyze death certificate data of Hispanic-classified men and women, aged 25 to 74 years, whose underlying cause of death was diabetes, between 1989 and 2018. Death certificate data from the USA National Center for Health Statistics was downloaded, as well as USA population estimates by age, sex, and ethnicity from the USA Census Bureau. The analyses were undertaken using JointPoint software and the Age–Period–Cohort Web Tool, both developed by the USA National Cancer Institute. Results: The analyses showed that between 1989 to 2018, age-and sex-standardized diabetes mortality rates among the least educated individuals were higher than those among the most educated individuals (both sexes together, p = 0.036; males, p = 0.053; females, p = 0.036). The difference between the least and most educated individuals became more pronounced in recent years, as shown by independent confidence intervals across the study period. Sex-based analyses revealed that the age-adjUSAted diabetes mortality rate had increased to a greater extent among the least educated males and females, respectively, than among the most educated. Conclusions: The results of the analyses demonstrated a powerful effect of low education on amenable mortality attributable to diabetes among the Hispanic population in the USA. As an increasing prevalence of diabetes among the least educated Hispanics has been reported, there is a great need to identify and implement effective preventive services, self-management, and quality care practices, that may assist in reducing the growing disparity among those most vulnerable, such as minority populations

The efficacy of exercise training for cutaneous microvascular reactivity in the foot in people with diabetes and obesity : secondary analyses from a randomized controlled trial

It is unclear if cutaneous microvascular dysfunction associated with diabetes and obesity can be ameliorated with exercise. We investigated the effect of 12-weeks of exercise training on cutaneous microvascular reactivity in the foot. Thirty-three inactive adults with type 2 diabetes and obesity (55% male, 56.1 +/- 7.9 years, BMI: 35.8 +/- 5, diabetes duration: 7.9 +/- 6.3 years) were randomly allocated to 12-weeks of either (i) moderate-intensity continuous training [50-60% peak oxygen consumption (VO2peak), 30-45 min, 3 d/week], (ii) low-volume high-intensity interval training (90% VO2peak, 1-4 min, 3 d/week) or (iii) sham exercise placebo. Post-occlusive reactive hyperaemia at the hallux was determined by laser-Doppler fluxmetry. Though time to peak flux post-occlusion almost halved following moderate intensity exercise, no outcome measure reached statistical significance (p > 0.05). These secondary findings from a randomised controlled trial are the first data reporting the effect of exercise interventions on cutaneous microvascular reactivity in the foot in people with diabetes. A period of 12 weeks of moderate-intensity or low-volume high-intensity exercise may not be enough to elicit functional improvements in foot microvascular reactivity in adults with type 2 diabetes and obesity. Larger, sufficiently powered, prospective studies are necessary to determine if additional weight loss and/or higher exercise volume is required

Effects of Cannabidiol on exercise physiology and bioenergetics : a randomised controlled pilot trial

Background: Cannabidiol (CBD) has demonstrated anti-inflammatory, analgesic, anxiolytic and neuroprotective effects that have the potential to benefit athletes. This pilot study investigated the effects of acute, oral CBD treatment on physiological and psychological responses to aerobic exercise to determine its practical utility within the sporting context. Methods: On two occasions, nine endurance-trained males (mean±SD V̇O2max: 57.4±4.0 mL·min−1 ·kg−1 ) ran for 60 min at a fixed intensity (70% V̇O2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2). Participants received CBD (300 mg; oral) or placebo 1.5 h before exercise in a randomised, double-blind design. Respiratory gases (V̇O2), respiratory exchange ratio (RER), heart rate (HR), blood glucose (BG) and lactate (BL) concentrations, and ratings of perceived exertion (RPE) and pleasure–displeasure were measured at three timepoints (T1–3) during RUN 1. V̇O2max, RERmax, HRmax and time to exhaustion (TTE) were recorded during RUN 2. Venous blood was drawn at Baseline, Pre- and Post-RUN 1, Post-RUN 2 and 1 h Post-RUN 2. Data were synthesised using Cohen’s dz effect sizes and 85% confidence intervals (CIs). Effects were considered worthy of further investigation if the 85% CI included±0.5 but not zero. Results: CBD appeared to increase V̇O2 (T2:+38±48 mL·min−1, dz: 0.25–1.35), ratings of pleasure (T1:+0.7±0.9, dz: 0.22–1.32; T2:+0.8±1.1, dz: 0.17–1.25) and BL (T2:+3.3±6.4 mmol·L−1, dz:>0.00–1.03) during RUN 1 compared to placebo. No differences in HR, RPE, BG or RER were observed between treatments. CBD appeared to increase V̇O2max (+119±206 mL·min−1, dz: 0.06–1.10) and RERmax (+0.04±0.05 dz: 0.24–1.34) during RUN 2 compared to placebo. No differences in TTE or HRmax were observed between treatments. Exercise increased serum interleukin (IL)-6, IL-1β, tumour necrosis factor-α, lipopolysaccharide and myoglobin concentrations (i.e. Baseline vs. Post-RUN 1, Post-RUN 2 and/or 1-h Post-RUN 2, p’s<0.05). However, the changes were small, making it difficult to reliably evaluate the effect of CBD, where an effect appeared to be present. Plasma concentrations of the endogenous cannabinoid, anandamide (AEA), increased Post-RUN 1 and Post-RUN 2, relative to Baseline and Pre-RUN 1 (p’s<0.05). CBD appeared to reduce AEA concentrations Post-RUN 2, compared to placebo (−0.95±0.64 pmol·mL−1, dz: −2.19, −0.79). Conclusion: CBD appears to alter some key physiological and psychological responses to aerobic exercise without impairing performance. Larger studies are required to confirm and better understand these preliminary findings

Comparison of selected exercise training modalities in the management of PCOS: a systematic review and meta-analysis to inform evidence-based guidelines

Summary: Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age that often presents with reproductive, metabolic, and psychological symptoms. While exercise is part of the management of PCOS, it is unclear which form of exercise may be most effective and for which outcomes. Aim: In order to inform the updated 2023 International evidence-based guideline for the assessment and management of polycystic ovary syndrome, this systematic review aimed to determine the exercise modality that provides the greatest improvement in anthropometric, metabolic, hormonal/reproductive, and psychological outcomes in adult women with PCOS. Methods: Five databases were searched from inception to July 2022. Studies eligible for inclusion consisted of those in a PCOS population, that compared two exercise modalities, and reported at least one anthropometric, metabolic, hormonal/reproductive, and/or psychological outcome. Screening, data extraction, and methodological quality assessments were conducted by two independent reviewers. Methodological quality assessment was performed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to determine the certainty of evidence. Meta-analysis was performed utilising Comprehensive Meta-Analysis software, Version 3. Results: Of the 4739 records identified, five unique studies were eligible for inclusion in the systematic review and meta-analysis, comprising a total of 216 individuals. Meta-analyses comparing high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on anthropometric, metabolic, and hormonal/reproductive parameters found no statistically significant differences in outcomes between groups, and the certainty of evidence was graded as low or very low. Results from single studies showed that HIIT was more effective than MICT for menstrual regularity (odds ratio [95% confidence interval] ​= ​7.875 [1.105, 56.125], p ​= ​0.039, very low certainty). HIIT vs resistance training, and diet ​+ ​MICT vs diet ​+ ​MICT ​+ ​resistance training were examined by a single study each, and no statistically significant differences were found for any outcome, with the certainty of evidence ranked as very low. Conclusion: To date, there are insufficient RCTs comparing exercise modalities in individuals with PCOS to establish with certainty whether one form of exercise is superior to another for the management of PCOS

Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome

STUDY QUESTION What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients 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. STUDY FUNDING/COMPETING INTEREST(S) This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker’s fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker’s fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker’s fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker’s fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker’s fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC

Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Study question What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary answer International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. What is known already The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from 6 continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low- to low-quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus-based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, the evidence quality was low, and evidence-practice gaps persist. Study design, size, and duration The 2023 International Evidence-based Guideline update re-engaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength, and diversity and inclusion were considered throughout. Participants/materials, setting, and methods This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health, and other experts, alongside consumers, project management, evidence synthesis, statisticians, and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and 5 face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across 5 guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council. Main results and the role of chance The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care, and shared decision-making to improve patient experience, alongside greater research; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management. Limitations and reasons for caution Overall, recommendations are strengthened and evidence is improved but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. Wider implications of the findings The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients 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 programme supports the guideline with an integrated evaluation programme