Laser and Light-Based Therapies for Hirsutism Management in Women With Polycystic Ovarian Syndrome: A Systematic Review.

Importance: Hirsutism represents a significant concern for women with polycystic ovary syndrome (PCOS), with deleterious psychological effects warranting acknowledgment and a clear imperative to provide effective management. To our knowledge, this is the first review to exclusively examine the effectiveness of laser and light-based therapies in addressing hirsutism in women with PCOS. Objective: To synthesize the existing literature regarding the effectiveness of laser and light hair reduction therapies, either as stand-alone treatments or in combination with systemic agents, in treating hirsutism for women with PCOS. Evidence Review: A systematic literature review was performed using MEDLINE, Embase, EMCARE, and CINAHL according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Articles written in English, reporting on patients who met pre-established inclusion criteria were selected. Objective and subjectively measured outcomes relating to the effect of laser or light-based hair reduction therapies on hirsutism were abstracted. Heterogeneity among included studies precluded a meta-analysis, necessitating a narrative synthesis. Findings: Six studies reporting data on 423 individual patients with PCOS who underwent laser or light-based hair reduction therapies were included: 4 randomized clinical trials and 2 cohort studies. Alexandrite laser demonstrated significant improvements in hirsutism severity and psychological outcomes, particularly at high-fluence application. Alexandrite laser was also found to be more effective than intense pulsed light (IPL). The combination of diode laser with either metformin or combined oral contraceptive pill was superior to the application of diode laser alone, just as the addition of metformin to IPL demonstrated superior results to IPL treatment alone. Overall, most interventions were well tolerated. The overall certainty of evidence across all outcomes and comparisons was limited in part due to the observational nature of some studies. Conclusions and Relevance: This systematic review highlights the potential of laser and light hair reduction therapies, both as stand-alone treatments and in combination with other pharmacological agents in PCOS. However, this review was limited by low certainty of the evidence, few studies evaluating effectiveness and safety in those with skin of color, and heterogeneity in outcome assessment. Future studies are needed to provide more robust evidence among diverse individuals with PCOS and hirsutism.

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.

Diagnostic accuracy of oral glucose tolerance tests, fasting plasma glucose and haemoglobin A1c for type 2 diabetes in women with polycystic ovary syndrome: A systematic review and meta-analysis.

AIMS: To inform international guidelines, a systematic review and meta-analysis was conducted to assess the performance of diagnostic methods for type 2 diabetes in women with polycystic ovary syndrome (PCOS). METHODS: An updated systematic search was conducted on five databases from 2017 until October 2023 and combined with prior searches (from inception). Meta-analyses of diagnostic accuracy tests were conducted. RESULTS: Nine studies comprising 2628 women with PCOS were included. Against the oral glucose tolerance test, a haemoglobin A1C (HbA1c) ≥ 6.5% had a pooled sensitivity of 50.00% (95% confidence interval (CI): 35.53-64.47), specificity of 99.86% (95%CI: 99.49-99.98), and positive and negative predictive values of 92.59% (95%CI: 75.27-98.09) and 98.27% (95%CI: 97.73-98.68), respectively, with an accuracy of 98.17% (95%CI: 97.34-98.79). Fasting plasma glucose values ≥ 7.0 mmol/L had a pooled sensitivity of 58.14% (95%CI: 42.13-72.99), specificity of 92.59% (95%CI: 75.35-98.08), positive and negative predictive values of 92.59% (95%CI: 75.35-98.08) and 99.09% (95%CI: 98.71-99.36), respectively, and an accuracy of 99.00% (95%CI: 98.46-99.39) against the oral glucose tolerance test. CONCLUSIONS: To our knowledge, this is the first systematic review assessing the performance of diagnostic methods for type 2 diabetes in women with PCOS. We demonstrate that using a cut-off for HbA1c of ≥6.5% in this population may result in misdiagnosis of half of the women with type 2 diabetes. Our results directly informed the recommendations of the 2023 International PCOS Guideline, suggesting that the oral glucose tolerance test is the optimal method for screening and diagnosing type 2 diabetes in women with PCOS and is superior to fasting plasma glucose and HbA1c.

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.

Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory. OBJECTIVE AND RATIONALE: The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS. SEARCH METHODS: Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias. OUTCOMES: There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P = 0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes. WIDER IMPLICATIONS: Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sexual function in PCOS. Future research needs to assess both psychosexual function and distress to aid in understanding the degree of psychosexual dysfunction in PCOS. Finally, more diverse populations (e.g. non-heterosexual and more ethnically diverse groups) should be included in future studies and the efficacy of treatments for sexual dysfunction should also be assessed (e.g. lifestyle and pharmacological interventions).

Assessing the influence of preconception diet on male fertility: a systematic scoping review.

BACKGROUND: The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes. OBJECTIVE AND RATIONALE: The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes. SEARCH METHODS: Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters. OUTCOMES: A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a 'healthy diet' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health. WIDER IMPLICATIONS: Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing consumption of sugar-sweetened beverages and processed meat, but it is unclear whether these benefits extend beyond sperm parameters to improve clinical fertility. More studies exploring whole diets rather than singular foods or nutritional components in the context of male fertility are encouraged, particularly by means of RCTs where feasible. Further assessment of core fertility outcomes is warranted and requires careful planning in high-quality prospective studies and RCTs. These studies can lay the groundwork for targeted dietary guidelines and enhance the prospects of successful fertility outcomes for men in the preconception period. Systematic search of preconception diet suggests that increasing fish and reducing sugary drinks, processed meats and total fat may improve male fertility, while consuming healthy diets, fish, fats/fatty acids, carbohydrates and dairy and reducing processed meat can improve sperm health.

Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women. OBJECTIVE: As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated. DATA SOURCES: Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched. STUDY SELECTION: Women with PCOS included in randomized controlled trials (RCTs). DATA EXTRACTION: We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed. DATA SYNTHESIS: The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/L; 95% CI -174.46, -62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (-16.61 nmol/L; 95% CI -28.51, -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/L; 95% CI -40.65, -13.59) and triglycerides (-0.15 mmol/L; 95% CI -0.29, -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment. CONCLUSIONS: The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).

Bridging the Information Gap in Polycystic Ovary Syndrome: A Narrative Review with Systematic Approach.

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy with wide-ranging implications for affected individuals. Literature has shown that patients with PCOS are dissatisfied with the health information provided to them and that healthcare professionals lack adequate knowledge. In this narrative review with systematic approach, we explored the unmet information needs in PCOS care for both patients and healthcare professionals. A comprehensive search of databases yielded 41 relevant studies, predominantly of observational and qualitative design. Adults and adolescents with PCOS desire wide ranging health information and express a keen desire for weight management guidance. Importantly, discussions surrounding weight should be addressed knowledgeably and without weight bias. Therefore, healthcare professionals should facilitate access to comprehensive evidence-based resources. Lack of information drives PCOS-related online searches. Referral to support groups that promote individual agency in the self-management aspects of PCOS can furthermore guide patient resource acquisition. Patients prefer guidance from professionals that understand the psychosocial complexity of PCOS and can empathize with experiences of stigmatization or even marginalization depending on the cultural context of the individual. The findings informed the 2023 International Evidence-Based PCOS Guideline, recommending patient-centered communication, evidence-based information resources, and culturally sensitive approaches to optimize PCOS care.

High prevalence of medical conditions and unhealthy lifestyle behaviours in women with PCOS during preconception: findings from the Australian Longitudinal Study on Women's Health.

STUDY QUESTION: What are the pre-existing medical conditions and lifestyle behaviours of women with and without PCOS during the preconception period? SUMMARY ANSWER: During the preconception period, medical conditions of obesity, depression, anxiety, and a history of infertility were more highly prevalent in women with than without PCOS, and more women with than without PCOS were engaged in unhealthy lifestyle behaviours. WHAT IS KNOWN ALREADY: Women with PCOS are predisposed to infertility and pregnancy complications. Optimizing preconception medical health and lifestyle behaviours can improve maternal and pregnancy outcomes but, to the best of our knowledge, no study has examined the preconception medical conditions and lifestyle behaviours of women with PCOS. STUDY DESIGN, SIZE DURATION: This is a cross-sectional study on 942 women with PCOS and 7024 women without PCOS, aged 24-30 years from the Australian Longitudinal Study of Women's Health, an ongoing, national survey-based prospective cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The current study analysed self-reported data from Survey 6 collected in 2019 of the cohort of women born between 1989 and 1995. Explored outcomes included BMI, pre-existing medical conditions, and modifiable lifestyle behaviours, including smoking, recreational drug use, alcohol intake, and physical activity level, during the preconception period. Differences between subgroups were tested using Student's t-test, χ2 test, or Fisher's exact test as appropriate. The associations of pregnancy intention with medical conditions and lifestyle behaviours were examined using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Obesity, depression, anxiety, and infertility were highly prevalent in women actively planning for pregnancy. Among women with PCOS, the prevalence of obesity was 47.02%, followed by depression at 32.70%, anxiety at 39.62%, and infertility at 47.17%. Conversely among women without PCOS, the corresponding prevalence was lower, at 22.33% for obesity, 18.98% for depression, 23.93% for anxiety, and 16.42% for infertility. In women actively planning for pregnancy, only those without PCOS demonstrated a lower prevalence of unhealthy lifestyle behaviours compared to non-planning women. The prevalence of unhealthy lifestyle behaviours was similar in women with PCOS regardless of their pregnancy intentions. Multivariable logistic regression revealed that only moderate/high stress with motherhood/children (adjusted odds ratio (OR) 3.31, 95% CI 1.60-6.85) and history of infertility (adjusted OR 9.67, 95% CI 5.02-18.64) were significantly associated with active pregnancy planning in women with PCOS. LIMITATIONS, REASONS FOR CAUTION: The findings were based on self-reported data. The cohort of women surveyed may have a higher level of education than women in the community, therefore our findings may underestimate the true prevalence of pre-existing medical conditions and lifestyle challenges faced by the broader population. WIDER IMPLICATIONS OF THE FINDINGS: A higher proportion of women with than without PCOS had pre-existing medical conditions and engaged in potentially modifiable unhealthy lifestyle behaviours during preconception despite their risk for subfertility and pregnancy complications. Healthcare professionals play a pivotal role in guiding this high-risk group of women during this period, offering counselling, education, and support for the adoption of healthy lifestyles to improve fertility, pregnancy outcomes, and intergenerational health. STUDY FUNDING/COMPETING INTEREST(S): C.T.T. holds a seed grant from the National Health and Medical Research Council (NHMRC) through the Centre of Research Excellence in Women's Health in Reproductive Life (CRE WHiRL) and Royal Australasian College of Physician Foundation Roger Bartop Research Establishment Fellowship. H.T. holds an NHMRC Medical Research Fellowship. C.L.H. holds an NHMRC CRE Health in Preconconception and Pregnancy Senior Postdoctoral Fellowship. A.E.J. holds a CRE WhiRL Early to Mid-career Fellowship. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

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.

Body image concerns in women with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To assess differences in body image concerns among women with and without polycystic ovary syndrome (PCOS). DESIGN: This is a systematic review and meta-analysis. METHODS: Electronic databases (MEDLINE, EMBASE, APA PsychInfo, PUBMED, Web-of-Science Core Collection, and Cochrane Controlled Register of Trials [CENTRAL]) were searched from inception through July 2022. Outcome measures included validated questionnaires reporting on body image concerns. Methodological quality was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system, and included studies were assessed for risk of bias. Meta-analyses were performed using the inverse variance method based on random or fixed effects models (Review Manager, Version 5). RESULTS: A total of 918 women with PCOS and 865 women without PCOS from 9 studies were included. Meta-analysis of 3 studies using Multidimensional Body-Self Relations Questionnaire Appearance Scale (MBSRQ-AS) showed those with PCOS reported higher dissatisfaction with appearance evaluation and appearance orientation compared to those without PCOS (mean difference [MD] = -0.78, I2 = 0%, P < .00001, and MD = 0.22, I2 = 54%, P = .004, respectively). Meta-analysis of 2 studies showed higher dissatisfaction with overweight preoccupation, lower body area satisfaction, and body weight classification on MBSRQ-AS subscales in those with PCOS compared to those without PCOS (all P < .001). Meta-analysis of 2 studies using the Body Esteem Scale for Adolescents and Adults (BESAA) showed significantly lower scores for the weight subscale in those with PCOS compared to those without PCOS (P = .03). CONCLUSIONS: Those with PCOS experience more significant body image concerns, emphasising the importance of awareness in the clinical care of PCOS. Considering the limited evidence, further studies are warranted to identify drivers and mitigating factors.

A systematic review of models of care for polycystic ovary syndrome highlights the gap in the literature, especially in developing countries.

Introduction: The aim of the study was to identify available polycystic ovary syndrome (PCOS) models of care (MoCs) and describe their characteristics and alignment with the international PCOS guideline. Methods: Ovid MEDLINE, All EBM, PsycINFO, Embase, and CINAHL were searched from inception until 11 July 2022. Any study with a description of a PCOS MoC was included. Non-evidence-based guidelines, abstracts, study protocols, and clinical trial registrations were excluded. We also excluded MoCs delivered in research settings to minimize care bias. Meta-analysis was not performed due to heterogeneity across MoCs. We describe and evaluate each MoC based on the recommendations made by the international evidence-based guideline for assessing and managing PCOS. Results: Of 3,671 articles, six articles describing five MoCs were included in our systematic review. All MoCs described a multidisciplinary approach, including an endocrinologist, dietitian, gynecologist, psychologist, dermatologist, etc. Three MoCs described all aspects of PCOS care aligned with the international guideline recommendations. These include providing education on long-term risks, lifestyle interventions, screening and management of emotional well-being, cardiometabolic diseases, and the dermatological and reproductive elements of PCOS. Three MoCs evaluated patients' and healthcare professionals' satisfaction, with generally positive findings. Only one MoC explored the impact of their service on patients' health outcomes and showed improvement in BMI. Conclusion: There is limited literature describing PCOS MoCs in routine practice. Future research should explore developing cost-effective co-created multidisciplinary PCOS MoCs globally. This may be facilitated by the exchange of best practices between institutions with an established MoC and those who are interested in setting one up. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346539, identifier CRD42022346539.

Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

Background: Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS. Methods: We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640. Findings: From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n = 961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens + lifestyle were superior to metformin + lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]: -1.59 [-3.06, -0.12], p = 0.03; I2 = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; I2 = 0%), fasting insulin and fasting insulin: glucose ratio (-2.11 µU/ml [-3.97, -0.26], p = 0.03; I2 = 0% and -1.12 [-1.44, -0.79], p < 0.0001, I2 = 0%, respectively), but were not superior to placebo + lifestyle for hirsutism (-0.93, [-3.37, 1.51], p = 0.45; I2 = 76%) or SHBG (9.72 nmol/l [-0.71, 20.14], p = 0.07; I2 = 31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58, -2.39], p < 0.0001, I2 = 1%), and resulted in lower androstenedione levels (-0.30 ng/ml [-0.50, -0.10], p = 0.004; I2 = 0%). Combination treatment with anti-androgens + metformin + lifestyle resulted in lower testosterone compared with metformin + lifestyle (-0.29 nmol/l [-0.52, -0.06], p = 0.01; I2 = 61%), but there were no differences in hirsutism when anti-androgens + metformin + lifestyle were compared with either anti-androgens + lifestyle or metformin + lifestyle. In limited meta-analyses (n = 2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP ± placebo, with no differences in other outcomes. Interpretation: Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics. Funding: National Health and Medical Research Council (NHMRC) of Australia Monash University.

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 remain 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 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 the 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 sponsoring 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 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 remain 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 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 the 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 sponsoring 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.

The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps remain regarding its efficacy and the specific outcomes in this population. This review evaluates the effectiveness of metformin and lifestyle modification compared with placebo in the management of PCOS and will inform the forthcoming, 2023 evidence-based PCOS guidelines. DESIGN: Systematic review and meta-analysis of the literature. METHODS: A search was performed in MEDLINE, EMBASE, PsycINFO, All EBM, and CINAHL. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomized controlled trials published in English through July 2022. RESULTS: Moderate certainty of evidence showed a larger reduction of body mass index (BMI) (mean difference [MD] -0.53, 95% confidence interval [CI] -0.95 to -0.12 kg/m2), homeostatic model assessment for insulin resistance (MD -0.50, 95% CI -0.91 to -0.09) (critical outcomes), and fasting glucose (MD -0.13, 95% CI -0.19 to -0.07 mmol/L) with metformin compared to placebo with increased mild gastrointestinal adverse effects (odds ratio [OR] 7.67, 95% CI 2.74-21.46). Low certainty of evidence showed a larger reduction of waist-hip ratio (MD -0.02, 95% CI -0.03 to -0.00), total cholesterol (MD -0.24, 95% CI -0.43 to -0.05 mmol/L), low-density lipoprotein (MD -0.16, 95% CI -0.30 to -0.01 mmol/L), and triglycerides (MD -0.11, 95% CI -0.20 to -0.02 mmol/L) with metformin than placebo. CONCLUSIONS: Metformin should be considered an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance, and lipids.

Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS). DESIGN: A systematic review and meta-analysis was performed, Prospero CRD42022345640. METHODS: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials. RESULTS: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified. CONCLUSION: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS. TRIAL REGISTRATION: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.