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      Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis

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          Abstract

          BACKGROUND

          Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these associations are lacking.

          OBJECTIVE AND RATIONALE

          Is PCOS a risk factor for cardiometabolic disease?

          SEARCH METHODS

          We searched from inception to September 2019 in MEDLINE and EMBASE using controlled terms (e.g. MESH) and text words for PCOS and cardiometabolic outcomes, including cardiovascular disease (CVD), stroke, myocardial infarction, hypertension (HT), type 2 diabetes (T2D), metabolic syndrome and dyslipidaemia. Cohort studies and case–control studies comparing the prevalence of T2D, HT, fatal or non-fatal CVD and/or lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) between women with and without PCOS of ≥18 years of age were eligible for this systematic review and meta-analysis. Studies were eligible regardless of the degree to which they adjusted for confounders including obesity. Articles had to be written in English, German or Dutch. Intervention studies, animal studies, conference abstracts, studies with a follow-up duration less than 3 years and studies with less than 10 PCOS cases were excluded. Study selection, quality assessment (Newcastle–Ottawa Scale) and data extraction were performed by two independent researchers.

          OUTCOMES

          Of the 5971 identified records, 23 cohort studies were included in the current systematic review. Women with PCOS had increased risks of HT (risk ratio (RR): 1.75, 95% CI 1.42 to 2.15), T2D (RR: 3.00, 95% CI 2.56 to 3.51), a higher serum concentration of TC (mean difference (MD): 7.14 95% CI 1.58 to 12.70 mg/dl), a lower serum concentration of HDL-C (MD: −2.45 95% CI −4.51 to −0.38 mg/dl) and increased risks of non-fatal cerebrovascular disease events (RR: 1.41, 95% CI 1.02 to 1.94) compared to women without PCOS. No differences were found for LDL-C (MD: 3.32 95% CI −4.11 to 10.75 mg/dl), TG (MD 18.53 95% CI −0.58 to 37.64 mg/dl) or coronary disease events (RR: 1.78, 95% CI 0.99 to 3.23). No meta-analyses could be performed for fatal CVD events due to the paucity of mortality data.

          WIDER IMPLICATIONS

          Women with PCOS are at increased risk of cardiometabolic disease. This review quantifies this risk, which is important for clinicians to inform patients and to take into account in the cardiovascular risk assessment of women with PCOS. Future clinical trials are needed to assess the ability of cardiometabolic screening and management in women with PCOS to reduce future CVD morbidity.

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          Most cited references70

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

          David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
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            Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

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              Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

              Study Question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings: The international guideline for the assessment and management of PCOS provides clinicians 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): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC
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                Author and article information

                Contributors
                Journal
                Hum Reprod Update
                Hum Reprod Update
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                Nov-Dec 2020
                30 September 2020
                30 September 2020
                : 26
                : 6
                : 942-960
                Affiliations
                Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Amsterdam Reproduction and Development Research Institute, Amsterdam UMC , Amsterdam, The Netherlands
                Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Amsterdam Public Health Research Institute, Amsterdam UMC , Amsterdam, The Netherlands
                Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Department of Obstetrics and Gynaecology, University of Groningen, University Medical Centre Groningen , Groningen, The Netherlands
                Department of Epidemiology, University of Groningen, University Medical Centre Groningen , Groningen, The Netherlands
                Department of Gynaecology and Obstetrics, Ziekenhuis Amstelland , Amstelveen, The Netherlands
                Department of Gynaecology and Obstetrics, Wilhelmina Children's Hospital Birth Centre, University Medical Centre Utrecht , Utrecht, The Netherlands
                Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Amsterdam Reproduction and Development Research Institute, Amsterdam UMC , Amsterdam, The Netherlands
                Medical Library, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Department of Obstetrics and Gynaecology, Erasmus University Medical Centre , Rotterdam, The Netherlands
                Department of Internal Medicine, Erasmus University Medical Centre , Rotterdam, The Netherlands
                Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Amsterdam Reproduction and Development Research Institute, Amsterdam UMC , Amsterdam, The Netherlands
                Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands
                Amsterdam Public Health Research Institute, Amsterdam UMC , Amsterdam, The Netherlands
                Department of Obstetrics and Gynaecology, University of Groningen, University Medical Centre Groningen , Groningen, The Netherlands
                Author notes
                Correspondence address. Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. E-mail: v.wekker@ 123456amsterdamumc.nl https://orcid.org/0000-0002-7143-7299
                Author information
                http://orcid.org/0000-0002-7143-7299
                Article
                dmaa029
                10.1093/humupd/dmaa029
                7600286
                32995872
                434bb5e8-8162-4510-9e78-a7fe431f9e38
                © The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 26 April 2019
                : 15 June 2020
                Page count
                Pages: 19
                Funding
                Funded by: Dutch Heart Foundation;
                Award ID: 2013T085
                Categories
                Reviews
                AcademicSubjects/MED00460
                AcademicSubjects/MED00905

                Human biology
                cardiometabolic health,polycystic ovary syndrome,hypertension,type two diabetes mellitus,dyslipidaemia,systematic review,meta-analysis,long term

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