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Studies report interaction difficulties between patients with polycystic ovary syndrome (PCOS) and healthcare professionals (HCP). This systematic review and qualitative evidence synthesis aimed to collate and synthesize the existing peer-reviewed literature investigating challenges for people with PCOS when interacting with HCP. Medline, PsycInfo, EMBASE, All EBM and CINAHL were searched from 1990 to September 2022. Study risk of bias (RoB) was performed and all textual data relevant to challenging interactions between patients with PCOS and HCP were extracted and analysed using thematic synthesis. Of the 6353 studies identified, 28 were included. Two were appraised as high, four as moderate and 22 as low RoB. Four analytic themes were derived illustrating that interactions were challenging when: (i) medical information (PCOS, its management) was not shared in the best way; (ii) information provision and deliberation opportunities were insufficient to achieve outcomes that mattered to patients; (iii) interactions prompted but did not support patient activation; and (iv) health system-level barriers (e.g. policies and guidelines) were present or made worse by HCP behaviour. Future research should examine methods for the implementation and evaluation of established frameworks for sharing medical information and supporting patient agency in the context of PCOS care.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta-analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence-Based PCOS Guideline. METHODS AND RESULTS: A systematic review and meta-analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26-2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07-2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43-4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20-2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53-2.69]; I2 = 0%). Meta-analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity. CONCLUSIONS: This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence-Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high-risk condition.
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Doenças Cardiovasculares , Síndrome do Ovário Policístico , Guias de Prática Clínica como Assunto , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Medição de Risco/métodos , Fatores de Risco de Doenças Cardíacas , Medicina Baseada em Evidências , Fatores de RiscoRESUMO
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).
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Síndrome do Ovário Policístico , Disfunções Sexuais Fisiológicas , Humanos , Síndrome do Ovário Policístico/psicologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/fisiopatologia , Feminino , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Fisiológicas/epidemiologia , Comportamento Sexual/psicologia , Qualidade de VidaRESUMO
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.
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Índice de Massa Corporal , Síndrome do Ovário Policístico , Complicações na Gravidez , Resultado da Gravidez , Síndrome do Ovário Policístico/complicações , Humanos , Gravidez , Feminino , Aborto Espontâneo/epidemiologia , Fatores de Risco , Adulto , Diabetes Gestacional , Pré-Eclâmpsia , Cesárea , Ganho de Peso na GestaçãoRESUMO
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.
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Peso ao Nascer , Índice de Massa Corporal , Recém-Nascido de Baixo Peso , Síndrome do Ovário Policístico , Nascimento Prematuro , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Retardo do Crescimento Fetal/epidemiologia , Ganho de Peso na Gestação , Recém-Nascido Pequeno para a Idade Gestacional , Síndrome do Ovário Policístico/complicações , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Fatores de RiscoRESUMO
IMPORTANCE: As part of the 2023 international evidence-based polycystic ovary syndrome (PCOS) guideline, this meta-analysis investigated the inclusion of Anti-Müllerian hormone (AMH) levels in the diagnostic criteria for PCOS. OBJECTIVE: To answer the following three questions: 1) Are AMH levels effective in diagnosing PCOS in adult women? 2) Are AMH levels effective in diagnosing PCOS in adolescents? Are AMH levels effective in diagnosing polycystic ovarian morphology (PCOM)? DATA SOURCES: Searches were conducted in six databases until July 31, 2023. STUDY SELECTION AND SYNTHESIS: Eligible studies were those conducted in humans, published in English, and reporting sensitivity, specificity, and/or area under the curve values. Extracted data included study population, age, body mass index, AMH assay, cut-off value of AMH levels, sensitivity, specificity, and area under the curve values. The risk of bias was assessed using the quality assessment of diagnostic accuracy studies tool. A random effects model was used to test diagnostic accuracy. MAIN OUTCOMES: Pooled sensitivity and specificity to use AMH levels for PCOS diagnosis in adults as well as 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% confidence interval [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 levels for defining PCOM in adults in accordance with the diagnostic algorithm. Antimüllerian hormone levels alone are insufficient for PCOS diagnosis and are nonspecific for PCOM in adolescents. Multiple factors influence AMH levels and cause heterogeneity as well as limitations in this study. Consequently, no international cut-off value could be recommended, emphasizing the need for research on more individualized cut-off values.
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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.
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Remoção de Cabelo , Hirsutismo , Síndrome do Ovário Policístico , Feminino , Humanos , Terapia Combinada , Remoção de Cabelo/métodos , Hirsutismo/terapia , Hirsutismo/etiologia , Terapia a Laser/métodos , Terapia com Luz de Baixa Intensidade/métodos , Metformina/uso terapêutico , Metformina/administração & dosagem , Fototerapia/métodos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Resultado do TratamentoRESUMO
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.
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Glicemia , Diabetes Mellitus Tipo 2 , Jejum , Teste de Tolerância a Glucose , Hemoglobinas Glicadas , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Glicemia/análise , Hemoglobinas Glicadas/análise , Jejum/sangue , Biomarcadores/sangue , Biomarcadores/análise , PrognósticoRESUMO
CONTEXT: Polycystic ovary syndrome (PCOS) is associated with disordered eating/eating disorders, but prior meta-analyses are limited by small numbers. OBJECTIVE: To inform the 2023 International PCOS Guideline, we performed a systematic review and meta-analysis evaluating the prevalence of disordered eating/eating disorders among women with and without PCOS. METHODS: Ovid MEDLINE, EMBASE, PsycInfo, and All EMB were searched from inception through February 1, 2024, for studies that compared prevalences of eating disordered/disordered eating in adolescent or adult women. Random effects meta-analyses were used to estimate the pooled odds ratios (OR) or standardized mean differences (SMD) of outcomes in women with PCOS compared to controls. Methodological quality was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system, and included studies were assessed for risk of bias. RESULTS: Of 1352 articles identified, 20 were included, with a total of 28 922 women with PCOS and 258 619 controls. Individuals with PCOS had higher odds of any eating disorder (OR: 1.53 [1.29, 1.82], 8 studies), which persisted in studies where PCOS was diagnosed by Rotterdam criteria (OR: 2.88 [1.55, 5.34], 4 studies). Odds of bulimia nervosa, binge eating disorder, and disordered eating, but not anorexia nervosa, were increased in PCOS. Mean disordered eating scores were higher in PCOS (SMD: 0.52 [0.28, 0.77], 13 studies), including when stratified by normal and higher weight body mass index. Most included studies were of moderate quality, with no evidence of publication bias. CONCLUSION: Our study informs the 2023 PCOS Guideline recommendations for consideration of the risk of disordered eating/ eating disorders in care of women with PCOS, regardless of weight, especially during providing lifestyle counseling.
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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.
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Fármacos Antiobesidade , Metformina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Orlistate/uso terapêutico , Exenatida/uso terapêutico , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêuticoRESUMO
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.
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Dieta , Fertilidade , Humanos , Masculino , Gravidez , Feminino , Fertilidade/efeitos dos fármacos , Cuidado Pré-Concepcional/métodos , Taxa de GravidezRESUMO
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.