Exercise in the management of polycystic ovary syndrome: A position statement from Exercise and Sport Science Australia.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition amongst females of reproductive age, leading to lifelong cardiometabolic, reproductive, psychological, and dermatologic symptoms as well as a reduced quality of life. Lifestyle interventions, which can include structured exercise programmes delivered by appropriately trained exercise professionals such as clinical exercise physiologists, are considered first-line strategies in PCOS management due to their therapeutic effects on various health outcomes and quality of life. This position statement builds on the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS and describes the role of the exercise professional in the context of the multidisciplinary care team which includes physicians and allied health professionals. This position statement aims to equip exercise professionals with a broad understanding of the pathophysiology of PCOS, how it is diagnosed and managed in clinical practice, and evidence- and consensus-based recommendations for physical activity and exercise in PCOS management. In line with the physical activity recommendations for the general public, individuals with PCOS should aim to undertake between 150 to 300min of moderate-intensity or 75 to 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week. Additionally, muscle-strengthening activities on two non-consecutive days per week are recommended to maintain health and prevent weight gain. For further health benefits and to achieve modest weight loss, individuals with PCOS should aim for a minimum of 250min of moderate-intensity or 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week, plus muscle-strengthening activities on two non-consecutive days per week. Adolescents with PCOS should aim for a minimum of 60min moderate- to vigorous-intensity activity each day, incorporating muscle- and bone-strengthening activities three times per week. Finally, exercise professionals should consider the significant psychological burden, including weight stigma, and the high prevalence of comorbidities amongst individuals with PCOS and take appropriate measures to deliver safe and efficacious exercise interventions.

Systematic review and meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

Screening for polycystic ovary syndrome (PCOS) in antenatal care is inadequate, largely owing to the lack of clarity around whether PCOS is an independent risk factor for pregnancy complications. This systematic review and meta-analysis include 104 studies and 106,690 pregnancies in women with and without PCOS from inception until 13th July 2022. We report that women with PCOS are younger and have higher body mass index (BMI) around conception and have greater gestational weight gain. The odds of miscarriage, gestational diabetes mellitus, gestational hypertension, pre-eclampsia and cesarean section are higher in women with PCOS. The increased odds of adverse outcomes in PCOS remain significant when age and BMI are matched and when analyses are restricted to high-quality studies. This work informed the recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome, emphasizing that PCOS status should be captured in all women who are planning to, or have recently become pregnant to facilitate prevention of adverse outcomes and improve pregnancy outcomes.

Systematic review and meta-analysis of birth outcomes in women with polycystic ovary syndrome.

It is unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for adverse birth outcomes in the offspring of affected women. Here, we investigate the association of PCOS with birth outcomes in the offspring of women with PCOS overall and by potential confounders. This systematic review and meta-analysis included 73 studies and 92,881 offspring of women with and without PCOS from inception until 13th July 2022. We report that mothers with PCOS are younger and have higher body mass index (BMI) around conception and have greater gestational weight gain. The odds of preterm birth, fetal growth restriction and low birth weight are higher and mean birthweight is lower in PCOS of which a lower mean birthweight and a higher small for gestational age are probably independent of BMI. This work informed the recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome, emphasizing that PCOS status should be captured at pregnancy to identify risk and improve birth outcomes in the offspring.

Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.

AIMS: This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. METHODS: Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. RESULTS: Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. CONCLUSIONS: These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.

Anti-Müllerian hormone as a diagnostic biomarker for Polycystic Ovary Syndrome (PCOS) and Polycystic Ovarian Morphology (PCOM): a systematic review and meta-analysis.

IMPORTANCE: As part of the 2023 International Evidence-based PCOS Guideline, this meta-analysis investigated the inclusion of Anti-Müllerian Hormone (AMH) in the diagnostic criteria for Polycystic Ovary Syndrome (PCOS). OBJECTIVE: A systematic review and three meta-analyses were performed to answer the following three questions: 1) Is AMH effective to diagnose PCOS in adult women? 2) Is AMH effective to diagnose PCOS in adolescents? 3) Is AMH effective to diagnose PCOM? DATA SOURCES: Searches were conducted in six databases until July 31st 2023. STUDY SELECTION AND SYNTHESIS: Eligible studies were those conducted in humans, published in English and reported sensitivity, specificity, and/or area under the curve. Extracted data included study population, age, body mass index (BMI), AMH assay, cut off value of AMH, sensitivity, specificity, and area under the curve (AUC). Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects model were used to test diagnostic accuracy. MAIN OUTCOMES: Pooled sensitivity and specificity to use AMH for PCOS diagnosis in adults and adolescents, and for detecting PCOM in adults. RESULTS: Eighty-two studies were included. The adult AMH-PCOS meta-analyses (n = 68) showed a pooled sensitivity and specificity of 0.79 [95% CI 0.76; 0.82; I2 = 86%] and 0.87 [95% CI 0.84; 0.89; I2 = 91%]. The adolescent AMH-PCOS meta-analysis (n = 11) showed a pooled sensitivity and specificity of 0.66 [95% CI 0.58; 0.73; I2 = 74%] and 0.78 [95% CI 0.71; 0.83; I2 = 45%]. The adult AMH-PCOM meta-analysis (n = 7) showed a pooled sensitivity and specificity of 0.79 [95% CI 0.72; 0.85; I2 = 94%] and 0.87 [95% CI 0.78; 0.93; I2 = 94%]. CONCLUSION AND RELEVANCE: This study investigated the most profound change in the 2023 International Evidence-based PCOS Guideline, which now recommends AMH for defining PCOM in adults, in accordance with the diagnostic algorithm. AMH alone is insufficient for PCOS diagnosis and is nonspecific for PCOM in adolescents. Multiple factors influence AMH levels and caused heterogeneity and limitations in this study. Consequently, no international cut off value could be recommended, emphasizing the need for research on more individualized cut offs.

Maternal metabolic conditions as predictors of breastfeeding outcomes: Insights from an Australian cohort study.

INTRODUCTION: Breastfeeding represents an important opportunity to optimize health outcomes for both mother and infant, particularly in the context of maternal metabolic conditions such as diabetes and polycystic ovary syndrome. However, evidence suggests that women affected by these conditions breastfeed at reduced rates and durations. Our aim was to use the large, prospective, community-based Australian Longitudinal Study on Women's Health (ALSWH) to conduct an in-depth exploratory analysis of breastfeeding outcomes in Australian women affected by key maternal metabolic conditions. MATERIAL AND METHODS: Data from 12 920 pregnancies to 5605 women from the 1973-1978 birth cohort of the ALSWH were examined. Univariable and multivariable regression using generalized estimating equation models were applied to assess breastfeeding initiation and duration (outcome measures) in relation to key self-reported maternal metabolic diagnoses (pre-gestational type 1 and type 2 diabetes, gestational diabetes, and polycystic ovary syndrome; main explanatory variables). Key sociodemographic and clinical covariates were also considered. RESULTS: Results showed no significant association between specific maternal metabolic diagnoses (pre-gestational or gestational diabetes, or polycystic ovary syndrome) and breastfeeding outcomes. However, maternal body mass index emerged as a key predictor of suboptimal breastfeeding outcomes. Pregnancies affected by maternal obesity were associated with a 2.1-fold increase in the odds of not initiating breastfeeding, after adjusting for other key variables (95% CI 1.67 to 2.60, p < 0.01). Maternal overweight and obesity were, respectively, associated with an adjusted 1.4-fold (95% CI 1.20 to 1.55, p < 0.01) and 1.8-fold increase (95% CI 1.60 to 2.10, p < 0.01) in the odds of a breastfeeding duration less than 6 months. CONCLUSIONS: Maternal obesity, rather than any specific maternal metabolic condition, appears to be a key predictor of breastfeeding outcomes in Australian women.

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.

Carnosine/histidine-containing dipeptide supplementation improves depression and quality of life: systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Mental ill-health is a common and growing issue, affecting 1 in 8 individuals or 970 million people worldwide in 2019. Histidine-containing dipeptides (HCDs) have been suggested to mitigate some aspects of mental ill-health, but a quantitative synthesis of the evidence is lacking. Therefore, a systematic review and meta-analysis of randomized controlled trials was conducted. OBJECTIVE: To summarize the evidence on the effects of HCDs on mental health outcomes. DATA SOURCE: A systematic literature search was performed using electronic databases (Medline via Ovid, Embase via Ovid, Scopus, Google Scholar, and Cochrane) from inception to October, 2022. DATA EXTRACTION: Two authors independently extracted data using a structured extraction format. DATA ANALYSIS: Data analysis was performed using STATA version 17. Random-effects models were used, and heterogeneity was assessed using the I2 test. Quality appraisal was performed using the Cochrane risk-of-bias 2.0 tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. CONCLUSION: 5507 studies were identified, with 20 studies fulfilling the inclusion criteria. Eighteen studies comprising 776 participants were included in the meta-analysis. HCD supplementation (anserine/carnosine, l-carnosine, ß-alanine) caused a significant reduction in depression scores measured with the Becks Depression Inventory (-0.79; 95% CI: -1.24, -0.35; moderate certainty on GRADE) when compared with placebo. An increase in quality-of-life scores measured with the 36-item Short-Form survey (SF-36) (0.65; 95% CI: 0.00, 1.30) and low certainty on GRADE in HCDs (anserine/carnosine, l-carnosine, ß-alanine) when compared with placebo were found. However, the rest of the outcomes did not show a significant change between HCD supplementation and placebo. Although the number of studies included in the meta-analysis was modest, a significant mean reduction was observed in depression score as well as an increase in quality-of-life score for the HCD group when compared with placebo. Most of the studies included had small sample sizes with short follow-up periods and moderate to high risk of bias, highlighting the need for further, well-designed studies to improve the evidence base. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

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.

Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines.

CONTEXT: Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate. OBJECTIVE: To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS. DATA SOURCES: Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022. STUDY SELECTION: Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included. DATA EXTRACTION: Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second. DATA SYNTHESIS: Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited. CONCLUSION: The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.

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.

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).

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).

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.

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.

Effects of carnosine and histidine-containing dipeptides on biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis.

CONTEXT: Carnosine and histidine-containing dipeptides (HCDs) are suggested to have anti-inflammatory and antioxidative benefits, but their effects on circulating adipokines and inflammatory and oxidative stress biomarkers remain unclear. OBJECTIVES: The aim of the present systematic review and meta-analysis was to determine the impact of HCD supplementation on inflammatory and oxidative stress biomarkers. DATA SOURCES: A systematic search was performed on Medline via Ovid, Scopus, Embase, ISI Web of Science, and the Cochrane Library databases from inception to 25 January 2023. DATA EXTRACTION: Using relevant key words, trials investigating the effects of carnosine/HCD supplementation on markers of inflammation and oxidative stress, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) were identified. Meta-analyses were conducted using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). DATA ANALYSIS: A total of 9 trials comprising 350 participants were included in the present meta-analysis. Carnosine/HCD supplementation led to a significant reduction in CRP (WMD: -0.97 mg/L; 95% CI: -1.59, -0.36), TNF-α (WMD: -3.60 pg/mL; 95% CI: -7.03, -0.18), and MDA (WMD: -0.34 µmol/L; 95% CI: -0.56, -0.12) and an elevation in CAT (WMD: 4.48 U/mL; 95% CI: 2.43, 6.53) compared with placebo. In contrast, carnosine/HCD supplementation had no effect on IL-6, adiponectin, GSH, SOD, and TAC levels. CONCLUSION: Carnosine/HCD supplementation may reduce inflammatory and oxidative stress biomarkers, and potentially modulate the cardiometabolic risks associated with chronic low-grade inflammation and lipid peroxidation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

Type and Frequency in Use of Nutraceutical and Micronutrient Supplementation for the Management of Polycystic Ovary Syndrome: A Systematic Scoping Review.

Lifestyle strategies are considered first-line treatment for the management of polycystic ovary syndrome (PCOS). However, complementary therapies, including nutrient supplementation, have been identified as a potential adjunct therapy. Therefore, we systematically mapped the available literature to identify the type and frequency of the use of nutraceutical and micronutrient supplementation for the management of PCOS features. A systematic search of the literature was conducted using CINAHL, Cochrane reviews, Medline, PsycINFO, Scopus and LILACS. All types of study designs were included if they reported on the use of nutraceuticals and/or micronutrient supplementation on features of PCOS in women aged ≥18 years. A total of 344 articles were included. Forty-one supplements were identified, with the most frequently investigated being inositols (n = 86), vitamin D (n = 53), N-acetylcysteine (n = 27) and omega-3 fatty acids (n = 25). Reproductive outcomes were the most commonly reported (n = 285; 83%), followed by metabolic (n = 229; 67%), anthropometric (n = 197; 57%) and psychological (n = 8; 2%). Our results identified that nutraceutical and micronutrient supplementation require further investigation of psychological outcomes in women with PCOS. Moreover, adequately powered primary studies are warranted to investigate therapeutic doses needed for clinical benefits.