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.

Combined oral contraceptive pill compared with no medical treatment in the management of polycystic ovary syndrome: A systematic review.

OBJECTIVE: As part of the update of the International Evidence-Based Guidelines for the Assessment and Management of polycystic ovary syndrome (PCOS), a systematic review was performed to inform evidence-based recommendations. DESIGN: Systematic review. Only randomised controlled trial were included. PATIENTS: Women with PCOS; the use of combined oral contraceptive pills (COCP) was compared with no medical treatment. MEASUREMENTS: Outcomes were designed in collaboration with clinical experts, researchers, and consumers. Critical outcomes included hirsutism, irregular cycles, quality of life, body mass index (BMI), and weight. RESULTS: 1660 publications were identified, but only four studies were included. No studies could be combined for meta-analysis. COCP treatment improved cycle regularity compared with no medical treatment (100% vs. 0%, with low certainty of evidence). COCP showed no difference in improvement of hirsutism or BMI compared with placebo or lifestyle; a lower weight after COCP compared with no treatment (mean difference [MD] -8.0 (95% confidence interval, CI -11.67); -4.33 kg); and improvement in quality of life (MD 1.2 [95% CI 0.96]; 1.44), but these results were all very low certainty of evidence. CONCLUSION: Results show that COCP benefit cycle regulation, but other benefits or potential adverse effects were only identified with very low certainty of evidence. The COCP is frontline medical treatment in PCOS, but this is still based on established efficacy in the broader general population. Our results show that research in PCOS is seriously lacking and should be prioritised to capture core reproductive, metabolic and psychological outcomes important in PCOS.

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.

Challenges in diagnosis and understanding of natural history of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting 8%-13% of reproductive-aged women. The aetiology of the syndrome is complex, with genetic susceptibility, androgen exposure in early life and adiposity related dysfunction leading to perturbance in hypothalamic-ovarian function. PCOS clinical features are heterogeneous, with manifestations arising even in early adolescence, developing into multisystem reproductive, metabolic and psychological manifestations in adulthood. In this review, we will discuss challenges in the diagnosis of PCOS and understanding of the natural history of PCOS.

Negative associations of ideal family size achievement with hypertension, obesity and maternal age in women with and without polycystic ovary syndrome.

OBJECTIVE: To investigate lifetime reproductive outcomes and the relationship of ideal family size (IFS) achievement with metabolic, psychiatric and reproductive history in women with and without polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional. PATIENT(S): A total of 9034 women with (n = 778) and without self-reported PCOS (n = 8256) born between 1973 and 1978 in the Australian Longitudinal Study on Women's Health. MEASUREMENTS: Self-reported IFS achievement and total number of live births. RESULTS: Women with and without PCOS aspired for similar IFS. Compared with women without PCOS, significantly less women with PCOS achieved their IFS (53.08% vs. 60.47%, p < 0.001). Higher proportion of women with PCOS did not achieve a live birth (37.15% vs. 31.64%, p = 0.002) and their median total number of live births was also lower (1 vs. 2, p < 0.001) than women without PCOS. After controlling for sociodemographic factors, negative associations were observed between IFS achievement and PCOS status, various metabolic, psychiatric and reproductive history. However, only hypertension (adjusted odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.67-1.00), obesity (adjusted OR: 0.79, 95% CI: 0.69-0.90), history of in vitro fertilisation use (IVF) (adjusted OR: 0.49, 95% CI: 0.38-0.63) and maternal age at first childbirth (adjusted OR: 0.92, 95% CI: 0.91-0.93) remained inversely associated with achievement of IFS in further multivariable regression models. CONCLUSION: Metabolic conditions and reproductive history of maternal age at first childbirth and history of IVF use, but not psychological conditions, were associated with reduced odds of achieving IFS. Early family planning/initiation and optimisation of metabolic health may help to improve reproductive outcomes.

Where are we in understanding the natural history of polycystic ovary syndrome? A systematic review of longitudinal cohort studies.

STUDY QUESTION: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course? SUMMARY ANSWER: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS. WHAT IS KNOWN ALREADY: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research. STUDY DESIGN, SIZE, DURATION: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information. LIMITATIONS, REASONS FOR CAUTION: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations. STUDY FUNDING/COMPETING INTEREST(S): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare. REGISTRATION NUMBER: Prospero registration number: CRD42020165546.

Maternal metabolic factors and the association with gestational diabetes: A systematic review and meta-analysis.

Gestational diabetes (GDM) is associated with several adverse outcomes for the mother and child. Higher levels of individual lipids are associated with risk of GDM and metabolic syndrome (MetS), a clustering of risk factors also increases risk for GDM. Metabolic factors can be modified by diet and lifestyle. This review comprehensively evaluates the association between MetS and its components, measured in early pregnancy, and risk for GDM. Databases (Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, and Cochrane Library) were searched from inception to 5 May 2021. Eligible studies included ≥1 metabolic factor (waist circumference, blood pressure, fasting plasma glucose (FPG), triglycerides, and high-density lipoprotein cholesterol), measured at <16 weeks' gestation. At least two authors independently screened potentially eligible studies. Heterogeneity was quantified using I2 . Data were pooled by random-effects models and expressed as odds ratio and 95% confidence intervals (CIs). Of 7213 articles identified, 40 unique articles were included in meta-analysis. In analyses adjusting for maternal age and body mass index, GDM was increased with increasing FPG (odds ratios [OR] 1.92; 95% CI 1.39-2.64, k = 7 studies) or having MetS (OR 2.52; 1.65, 3.84, k = 3). Women with overweight (OR 2.17; 95% CI 1.89, 2.50, k = 12) or obesity (OR 4.34; 95% CI 2.79-6.74, k = 9) also were at increased risk for GDM. Early pregnancy assessment of glucose or the MetS, offers a potential opportunity to detect and treat individual risk factors as an approach towards GDM prevention; weight loss for pregnant women with overweight or obesity is not recommended. Systematic review registration: PROSPERO CRD42020199225.

Updated adolescent diagnostic criteria for polycystic ovary syndrome: impact on prevalence and longitudinal body mass index trajectories from birth to adulthood.

BACKGROUND: Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes. METHODS: Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14-16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations. RESULTS: PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p < 0.001). CONCLUSIONS: The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.

Physical activity and sedentary behaviour in women with and without polycystic ovary syndrome: An Australian population-based cross-sectional study.

OBJECTIVE: Lifestyle is the first-line treatment for women with polycystic ovary syndrome (PCOS). This study examines the physical activity (PA) levels and sedentary behaviours of women with and without PCOS, and their alignment with the PCOS PA guideline. METHODS: This cross-sectional study on women (aged 22-27 years) in the Australian Longitudinal Study on Women's Health was conducted in 2019 using data collected in 2017. Self-reported PA levels and total daily sitting time (ST) of women with (n = 7051) and without (n = 796) self-reported PCOS were presented, stratified by body mass index (BMI) and a combined overweight/obese group. RESULTS: 71.0% and 56.7% of the entire study cohort achieved PA levels recommended for weight maintenance and weight loss, respectively. Overall, PA levels were lower and ST was higher in women with than without PCOS. In each BMI category, similar proportions of women with and without PCOS met the PA guidelines but became lower as BMI category increased. Fewer overweight/obese group women with than without PCOS aligned with recommendations for weight maintenance (58.7% vs 65.7%, P = .003) or weight loss (45.1% vs 50.3%, P = .032). ST ≥8 h/d was observed in two-thirds of women with and without self-reported PCOS similarly before and after stratifying by BMI. CONCLUSION: High sedentary behaviour was extremely prevalent. Although the majority of women met PA recommendations for weight maintenance, only one in two overweight/obese women met PA recommendation for weight loss. Overweight/obese women with PCOS were more likely to participate in insufficient PA and require increased support to achieve sustainable healthy lifestyle.

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).

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.

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).

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.

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.

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.

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.

Polycystic ovary syndrome (PCOS): international collaboration to translate evidence and guide future research.

Polycystic ovary syndrome (PCOS) affects 8-13% of reproductive-aged women, impacts biopsychosocial factors and creates a significant health-related economic burden across the reproductive, metabolic and psychological spectrum of complications. Despite being a heterogenous condition, recent genomic studies indicate that PCOS, regardless of diagnostic criteria and clinical features, shares similar underlying biologic mechanisms. However, recent advances have shown that clinical reproductive and diagnostic features are poorly correlated to genotypes and do not represent true phenotypes. Until we have a better understanding of genetic and epigenetic influences on PCOS and long-term outcomes, targeted treatment is limited. In the interim, a unified approach to integrate evidence, optimise management and guide future research in PCOS is necessary. This has motivated an international collaboration to develop an International Evidence-Based PCOS Guideline to improve health outcomes in women with PCOS. Dissemination and translation of the guideline into health policy and clinical practice are crucial steps to close the knowledge--practice gap, guide future research and enhance positive impact on the health of women with PCOS. Here, we review the (i) understanding of aetiology and genetics of PCOS; (ii) development and translation efforts of the 2018 International Evidence-based PCOS Guideline; (iii) current progress and plans for the guideline update, including the involvement of an early career researcher network to assist with evidence synthesis and (iv) the opportunity to target and guide future research for PCOS.

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.