Abstract Androgen excess drives metabolic and reproductive complications in polycystic ovary syndrome (PCOS), affecting 10-15% of women globally. Aldo-keto reductase 1C3 (AKR1C3) converts inactive precursors from both the classic and the recently identified 11-oxygenated androgen pathways, generating testosterone and 11-ketotestosterone, respectively, which exert comparable androgen receptor activation. Both circulate in similar concentrations in premenopausal women while 11-ketotestosterone is predominant after menopause and in PCOS. Here, we show that adipocytes are a major site of AKR1C3 and androgen receptor expression, with increased expression in women and individuals with obesity. Using human female adipose tissue explants, we find a much higher activation of 11-oxygenated over classic androgens, observing a decrease in 11-oxygenated but not classic androgen activation by AKR1C3 inhibition. Correspondingly, we demonstrate that AKR1C3 inhibitor treatment in premenopausal women selectively disrupts the activation of 11-oxygenated androgens. Pharmacological targeting of AKR1C3 provides a novel strategy to alleviate systemic and intra-adipose 11-oxygenated androgen excess. One Sentence Summary Inhibition of the androgen-activating enzyme AKR1C3 results in a major decrease in 11-oxygenated but not classic androgens in women.

Obesity is a chronic disease associated with multiple health risks. Multimodal treatments including lifestyle interventions, pharmacotherapies and bariatric surgery should be the standard of care for obesity management. Bariatric surgery remains the most effective treatment yielding to sustainable weight loss (WL) of about 20-30%. Having understood better the role of the gut-brain axis on appetite, the field of obesity pharmacotherapy has been advancing rapidly. The recent approvals for glucagon-like peptide-1 (GLP-1) receptor agonist (RA) semaglutide 2.4 mg and the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide as treatments for obesity have raised the bar for WL efficacy for the emerging obesity pharmacotherapies. Combining GLP-1 RA and other entero-pancreatic hormones including GIP, glucagon or amylin receptor agonists (RAs) as well as GIP receptor antagonists have shown promising data in early phases of clinical trials, with some progressing to phase III clinical trials. Notably, the combinations of GLP-1 RA, GIP and glucagon RA (retatrutide) have shown WL efficacy closing on to that observed in bariatric surgery. While entero-pancreatic hormone-based therapies have been the centre of attention for obesity pharmacotherapies, non- entero-pancreatic hormone treatments also hold promise. In this review, we present the future pharmacotherapies for weight management in people with obesity, focusing on entero-pancreatic hormone-based molecules.

BACKGROUND:Intensive glucose management in people with diabetes and frailty presents significant risk which outweighs potential benefit. Hospital admission presents an opportunity for interventions that may reduce the impact of overtreatment in people with diabetes and frailty. Our previous study has shown low rates of glycated haemoglobin(HbA1c) assessment and inpatient medication deintensification in people with diabetes and frailty. METHODS:We conducted a three-intervention quality improvement programme and studied the effectiveness of the interventions aiming to improve the inpatient HbA1c assessment and management of inpatients with diabetes and frailty. A baseline assessment was conducted prior to cycles 1 and 2, with another audit conducted post-cycles 1 and 2. A further audit was then carried out with another audit post-cycle 3. INTERVENTIONS:Interventions 1 and 2 involved publishing an infographic to aid assessment and medication deintensification in patients with diabetes and frailty, followed by spreading awareness among resident doctors of the baseline audit results and the infographic via email and WhatsApp groups. Intervention 3 involved allocating 'Diafrailty Champion' the medical wards to help improve the assessment and management of patients with diabetes and frailty. RESULTS:A total of 291 patients with diabetes and moderate-severe frailty were included in our audits (96 patients in baseline audit, 102 post-cycles 1 and 2 audit, 92 post-cycle 3 'Diafrailty Champion' audit). Improvements were observed for the rates of HbA1c assessment and deintensification in the post-interventions 1 and 2 audit, and these persisted following the introduction of 'Diafrailty Champion'. CONCLUSIONS:Interventions that included raising awareness of the inpatient assessment and management of people with diabetes and frailty were successful in improving inpatient HbA1c assessment and deintensification rates. The improved HbA1c assessment and deintensification rates persist following the engagement of a resident doctor 'Diafrailty Champion'.

BACKGROUND:Medical education employs diverse teaching strategies, including blending lecture-based learning, small-group teaching (SGT) and, increasingly, simulation-based learning. Nonetheless, limitations in clinical application and participation persist. Simulation via Instant Messaging for Bedside Application (SIMBA) complements these methods by simulating real-world clinical scenarios. This pilot study compares SIMBA's effectiveness with SGT in endocrine topics for medical and pharmacy students. METHODS:The SIMBA for students model was developed using Kern's six-step framework. SIMBA sessions, facilitated by trained moderators and senior experts, simulated outpatient consultations via WhatsApp. The study included SIMBA and SGT sessions from October 2020 to March 2022. Teaching effectiveness was assessed through postsession surveys and multiple-choice questions (MCQs). The study compared the MCQ scores and student satisfaction of SIMBA, SGT and combined SIMBA + SGT cohorts. RESULTS:One hundred thirty (103 medical and 27 pharmacy) students participated in 14 SIMBA sessions, and 150 students responded to the post-SGT survey, with 38 attending both. Median MCQ scores were higher post-SIMBA (75.0%) compared with post-SGT (60.0%) (p < 0.0001). No significant difference was observed between SIMBA and SIMBA + SGT scores or SGT and SIMBA + SGT scores. SIMBA sessions were perceived as enjoyable (89.2%), intelligible (90.8%), engaging (81.5%), promoted new knowledge (90.0%) and enhanced comprehension (93.9%). 83.1% of students desired SIMBA to complement SGT. CONCLUSIONS:SIMBA demonstrated superior knowledge gain and student satisfaction compared to SGT. Its familiar technology and interactive format suit modern learning, offering a standardised and equitable experience. Integrating SIMBA into the curriculum could help overcome teaching limitations and better prepare students for clinical practice.

INTRODUCTION:People with diabetes and frailty require less intensive treatment of hyperglycaemia. Previous study has shown low rates of HbA1c assessment and deintensification for people with diabetes and frailty. Postgraduate doctors in training (PGDiT) is important in the inpatient management of people with diabetes and frailty. This study aims to assess the knowledge and management practice amongst PGDiT in managing people with diabetes and frailty and how this may translate to patients' clinical outcomes. METHODS:Three cross-sectional survey-based studies were conducted on PGDiT at the beginning of each 4-month rotation. Survey questions incorporated knowledge of HbA1c goals and on PGDiT deintensification practice in people with diabetes and frailty who are overtreated with blood glucose-lowering medication. These were coupled by two cross-sectional data collection on patients' outcomes conducted during the same period including HbA1c assessment and rates of deintensification. RESULTS:PGDiT survey: 160 PGDiT responded to the survey. 80.0% (n = 128/160) of PGDiT reported that they knew the target HbA1c in patients with diabetes and frailty. However, only 32.8% (n = 42/128) of these correctly indicated the target HbA1c for such patients. PGDiT deintensification practices were lower than expected and several barriers of inpatient deintensification were identified. Patients' clinical outcomes: 198 patients with diabetes and moderate-severe frailty were included in our analysis (median (interquartile range, IQR) age 80 (71-87) years with median (IQR) clinical frailty scale of 6 (6-7)). For patients who did not have their HbA1c assessed in the last 6 months preceding admission, only 18.1% (n = 13/72) had it assessed during admission. In patients who are overtreated, deintensification rate was 29.7% (n = 22/74). CONCLUSION:Our audit shows limited knowledge and management practices amongst PGDiT in the management of inpatients with diabetes and frailty that may contribute to low inpatient deintensification rate. Interventions are needed to improve patient outcomes and a model of care consisting of appropriate inpatient multidisciplinary team input to reduce treatment inertia.

It remains unclear whether the prevalence and incidence of complications varies with ethnicity in individuals with early-onset type 2 diabetes. We undertook a systematic review to investigate. We identified sparse published data, with no clear findings. More prospective studies are needed. Epidemiological studies should routinely stratify by ethnicity.

Background To evaluate the efficacy of SIMBA as an educational intervention for both HCPs and people with either PCOS or adrenal conditions and to study the change in knowledge of people with PCOS or adrenal conditions about the conditions and expectations from the HCPs involved in their care following SIMBA-PPI sessions. Methods Two SIMBA-PPI sessions (SIMBA-PPI Polycystic ovary syndrome (SIMBA-PCOS) and SIMBA-PPI Adrenal conditions (SIMBA-Adrenal conditions)) were conducted in September 2021 and March 2022. In both sessions, HCPs interacted with moderators on patient management through WhatsApp. Patients with respective conditions underwent workshop-style learning in the same cases. SIMBA-PCOS transcripts were also translated into Brazilian Portuguese and workshops were held in both Brazilian Portuguese and English. The two groups (HCPs and patients) were then brought together to discuss exploring gaps in knowledge and expectations. The Wilcoxon Signed-Rank test compared differences in pre- and post-SIMBA self-reported confidence levels in HCPs and patients. Qualitative data from the online recordings were transcribed and analysed with inductive thematic analysis to identify gaps in knowledge and expectations from managing the cases. Results 48 HCPs and 25 patients participated in our study. When compared to pre-SIMBA confidence levels, SIMBA-PPI sessions effectively improved clinicians' confidence in managing PCOS (40.5%, p < .001) and adrenal conditions (23.0%, p < .001) post-SIMBA. Patient participants' confidence in HCPs significantly increased in the PCOS session (SIMBA-PCOS: 6.25%, p = 0.01). Conclusions Integration of PPI into SIMBA improved HCPs' confidence in managing PCOS and adrenal conditions. SIMBA-PPI also improved patients' confidence in HCPs. Our findings suggest that participating in SIMBA-PPI sessions can reduce the gap in knowledge and expectations between patients and HCPs involved in their care.

Obesity is a chronic disease associated with increased risk of obesity-related complications and mortality. Our better understanding of the weight regulation mechanisms and the role of gut-brain axis on appetite has led to the development of safe and effective entero-pancreatic hormone-based treatments for obesity such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA). Semaglutide 2.4 mg once weekly, a subcutaneously administered GLP-1 RA approved for obesity treatment in 2021, results in 15–17% mean weight loss (WL) with evidence of cardioprotection. Oral GLP-1 RA are also under development and early data shows similar WL efficacy to semaglutide 2.4 mg. Looking to the next generation of obesity treatments, combinations of GLP-1 with other entero-pancreatic hormones with complementary actions and/or synergistic potential (such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) are under investigation to enhance the WL and cardiometabolic benefits of GLP-1 RA. Tirzepatide, a dual GLP-1/GIP receptor agonist has been approved for glycaemic control in type 2 diabetes as well as for obesity management leading in up to 22.5% WL in phase 3 obesity trials. Other combinations of entero-pancreatic hormones including cagrisema (GLP-1/amylin RA) and the triple agonist retatrutide (GLP-1/GIP/glucagon RA) have also progressed to phase 3 trials as obesity treatments and early data suggests that may lead to even greater WL than tirzepatide. Additionally, agents with different mechanisms of action to entero-pancreatic hormones (e.g. bimagrumab) may improve the body composition during WL and are in early phase clinical trials. We are in a new era for obesity pharmacotherapy where combinations of entero-pancreatic hormones approach the WL achieved with bariatric surgery. In this review, we present the efficacy and safety data for the pipeline of obesity pharmacotherapies with a focus on entero-pancreatic hormone-based treatments and we consider the clinical implications and challenges that the new era in obesity management may bring.

Context: There is limited knowledge about the disparities between the sexes in obesity prevalence and associated cardiovascular complications in low- and middle-income countries (LMICs).Objective: We undertook a systematic review and meta-analysis to assess sex-specific disparities in the prevalence of obesity and cardiometabolic diseases in LMICs, the burden in women, and variations by region, country's income status, setting, and time.Methods: We searched major databases from inception to March 2023. Two independent reviewers selected the studies, assessed their quality, and extracted data. We used DerSimonian and Laird random-effects models to obtain pooled estimates of odds ratios and 95% CI for the association between sex and obesity and cardiometabolic diseases, and multilevel random-effects logistic regression models to estimate the prevalence of relevant outcomes (PROSPERO CRD42019132609).Results: We included 345 studies (3 916 276 individuals). The odds of obesity were 2.72-fold higher in women than men (OR 2.72; 95% CI, 2.54-2.91). The sex-specific disparities varied by region, with the greatest disparities in Sub-Saharan Africa (OR 3.91; 95% CI, 3.49-4.39). Among women in LMICs, 23% (95% CI, 21%-25%) had obesity, 27% (95% CI, 24%-29%) had hypertension, and 7% (95% CI, 6%-9%) had type 2 diabetes. The prevalence of obesity and type 2 diabetes in women varied by region, country's income, and setting, with the highest prevalence in the Middle East and North Africa, upper-middle-income countries and urban settings. The odds of hypertension (OR 2.41; 95% CI, 1.89-3.08) and type 2 diabetes (OR 2.65; 95% CI, 1.76-3.98) were doubled in women with vs without obesity.Conclusion: There is an urgent need for a women-centred and region-stratified approach to tackle obesity awareness, treatment, and prevention in women in LMICs.

INTRODUCTION:Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients.METHODS:Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge.RESULTS:n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases.CONCLUSION:As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

IntroductionOur previous study has shown low rates of inpatient deintensification and high rates of adverse outcomes in people with diabetes and frailty1,2. The diabetes in reach (DiR) team consists of diabetologists working together with diabetes specialist nurses, proactively supporting non-specialists in the inpatient management of diabetes. This could be done either virtually or by face-to-face review in the medical ward. This study assessed the role of the DiR team in improving care for inpatients with diabetes and frailty.Materials and methodsWe included all people with diabetes and clinical frailty score ≥ 6 discharged from our medical unit in the year 2022. Data including demographics, medications and comorbidities were collected. Inpatient management and outcomes collected include involvement of the DiR team, deintensification rate, inpatient hypoglycaemia (defined by any episode of capillary blood glucose of < 4 mmol/L), inpatient mortality and 1-month readmission rates.Results and discussionSix hundred and sixty-five people with diabetes and frailty were included in our analysis. 51.9% (n = 345/665) were female with a median age of 79 years (71-86). 19% (n = 119/625) were deintensified during admission. DiR teams were involved in the care of 26.8% (n = 178/665) of the patients. People with inpatient hypoglycaemia were more likely to be reviewed by the DiR team compared to those without hypoglycaemia [aOR: 5.7 (95% CI: 3.7–8.6), p<0.001]. In patients who were deintensified, deintensification was done by the parent team in 38.7% (n = 46/119) and 61.3% (n=73/119) by the DiR team. Irrespective of hypoglycaemia, being reviewed by the DiR team was associated with increased odds of deintensification compared to those that were not reviewed by the DiR team [aOR: 4.2 (95% CI: 2.6–6.8), p<0.001]. No associations were seen between being reviewed by DiR with inpatient mortality and readmission rate.ConclusionThe majority of inpatient deintensification in people with diabetes and frailty was initiated by the DiR team, compared to the parent team. DiR could play an effective and important role in improving the inpatient deintensification rate in people with diabetes and frailty.

INTRODUCTION:The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes.METHODS:A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected.RESULTS:Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication).CONCLUSION:The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

IntroductionGlucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have changed the landscape of type 2 diabetes (T2D) management due to their cardio-renal benefits, their glucose-lowering efficacy and weight loss (WL) maintenance. However, the response to GLP-1 RA monotherapy is heterogeneous. Additionally, the majority of GLP-1 RAs are injectable treatments. Oral GLP-1 RAs and injectable combinations of GLP-1 with other entero-pancreatic hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin) are under development for T2D and obesity management.Areas coveredHerein, we review the data on (i) oral GLP-1 RAs (oral semaglutide 25/50 mg and orforglipron) and (ii) dual/triple agonists (tirzepatide, cagrilintide 2.4 mg/semaglutide 2.4 mg, survodutide, mazdutide, retatrutide) that have recently completed phase 3 trials for T2D or are currently in phase 3 clinical trials. Tirzepatide is the first approved dual agonist (GLP-1/GIP) for T2D and obesity management.Expert opinionWe are in a new era in T2D management where entero-pancreatic hormone-based treatments can result in >= 15% WL and euglycemia for many people with T2D. Multiple molecules with different mechanisms of action are under development for T2D, obesity and other metabolic complications. Data on their cardio-renal benefits, long-term efficacy and safety as well as their cost-effectiveness will better inform their position in treatment algorithms.

To the Editor: One of the silver linings of the COVID-19 pandemic was the development of various initiatives that expanded opportunities for medical students and early-career doctors to develop their teamwork, clinical learning, and leadership skills. Simulation via Instant Messaging–Birmingham Advance (SIMBA) is one such global collaborative medical education initiative.1 Prior to SIMBA, we were used to traditional mentorship at our institutions that often operate within disciplinary silos, limiting opportunities for cross-pollination of ideas. Through SIMBA, we were able to collaborate with interdisciplinary teams, helping us break down the traditional silos and create a fertile ground to tackle multifaceted health care challenges. As each of us, including our mentor, was from different cultural backgrounds, we learned to navigate and appreciate the nuances of diverse perspectives when we came together. This cross-cultural competence is invaluable in today's globalized world, where health care challenges often transcend geographical boundaries. We called our experience "Mentorship Without Borders," which equipped us with the skills necessary to address the complexities of diverse patient populations and to collaborate effectively in international research endeavors that are the need of the hour. Our exposure to an expansive network enriched our understanding and empowered us to advocate for inclusivity within our respective fields. We were provided a platform to access opportunities and networks that may have been otherwise unavailable to us, bridging the academic gap between low-, middle-, and high-income countries. This inspired us to pay it forward and pave the way for a more equitable health care community with involvement from underrepresented individuals. The transformative impact of Mentorship Without Borders calls for a paradigm shift in how we approach mentorship and apprenticeship. Widespread adoption of Mentorship Without Borders can be facilitated through determining clear objectives, developing mentor-mentee matching strategies, using open-access technologies, and establishing communication channels for critical assessment. Mentorship should be viewed as a dynamic and evolving process that extends beyond a specific discipline or institution. Now, as the roles reverse with us becoming the mentors of trainees through SIMBA, our reflections highlight the power of mentor-mentee relationships in shaping the trajectory of aspiring health care professionals. By sharing our experiences, we hope others seek mentorship opportunities that transcend traditional boundaries and develop supportive ecosystems that propel them toward personal and professional growth. Kashish Malhotra, MBBS Trainee doctor, Dayanand Medical College and Hospital, Punjab, India, and honorary clinical research fellow, Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; email: [email protected]; ORCID: https://orcid.org/0000-0002-6985-5731 Meri Davitadze, MD Honorary clinical research fellow, Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom, and PhD student, Ilia State University, Tbilisi, Georgia; ORCID: https://orcid.org/0000-0002-8130-1213 Eka Melson, MSc Honorary clinical research fellow, Institute of Applied Health Research, University of Birmingham, Birmingham, and academic clinical fellow, Leicester Diabetes Centre, University of Leicester, Leicester, United Kingdom; ORCID: https://orcid.org/0000-0003-0685-4819

Abstract 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.