-
The Journal of Clinical Endocrinology... Sep 2023What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer...
STUDY QUESTION
What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?
SUMMARY ANSWER
International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.
WHAT IS KNOWN ALREADY
The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.
STUDY DESIGN, SIZE, DURATION
The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).
MAIN RESULTS AND THE ROLE OF CHANCE
The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.
LIMITATIONS, REASONS FOR CAUTION
Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.
WIDER IMPLICATIONS OF THE FINDINGS
The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.
STUDY FUNDING/COMPETING INTEREST(S)
This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
Topics: Pregnancy; Adult; Female; Humans; Child; Polycystic Ovary Syndrome; Quality of Life; Australia; Risk Factors; Infertility, Female
PubMed: 37580314
DOI: 10.1210/clinem/dgad463 -
Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing.International Journal of Molecular... Jan 2022Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS... (Review)
Review
Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.
Topics: Disease Management; Drug Repositioning; Female; Humans; Hyperandrogenism; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 35054768
DOI: 10.3390/ijms23020583 -
The Journal of Clinical Endocrinology... Jul 2021Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and...
CONTEXT
Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS).
EVIDENCE ACQUISITION
We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool.
EVIDENCE SYNTHESIS
We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease (12/13, 92%), followed by cardiovascular risk assessment (10/13, 77%). Mental health (8/13, 62%) and diagnosis in adolescents (7/13, 54%) were the least reported domains. Most CPGs had a high quality for scope and purpose description (12/13, 92%) while stakeholder's involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs (2/13, 15%). We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS.
CONCLUSION
Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates.
Topics: Disease Management; Evidence-Based Medicine; Female; Humans; Polycystic Ovary Syndrome; Practice Guidelines as Topic; Quality Assurance, Health Care
PubMed: 33839790
DOI: 10.1210/clinem/dgab232 -
Fertility and Sterility May 2022Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is hallmarked by hyperandrogenism, oligo-ovulation, and... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is hallmarked by hyperandrogenism, oligo-ovulation, and polycystic ovarian morphology. Polycystic ovary syndrome, particularly the hyperandrogenism phenotype, is associated with several cardiometabolic abnormalities, including obesity, dyslipidemia, elevated blood pressure, and prediabetes or type 2 diabetes. Many, but not all, studies have suggested that PCOS is associated with increased risk of cardiovascular disease (CVD), including coronary heart disease and stroke, independent of body mass index and traditional risk factors. Interpretation of the data from these observational studies is limited by the varying definitions and ascertainment of PCOS and CVD across studies. Recent Mendelian randomization studies have challenged the causality of PCOS with coronary heart disease and stroke. Future longitudinal studies with clearly defined PCOS criteria and newer genetic methodologies may help to determine association and causality. Nevertheless, CVD risk screening remains critical in this patient population, as improvements in metabolic profile and reduction in CVD risk are achievable with a combination of lifestyle management and pharmacotherapy. Statin therapy should be implemented in women with PCOS who have elevated atherosclerotic CVD risk. If CVD risk is uncertain, measurement of subclinical atherosclerosis (carotid plaque or coronary artery calcium) may be a useful tool to guide shared decision-making about initiation of statin therapy. Other medications, such as metformin and glucagon-like peptide-1 receptor agonists, also may be useful in reducing CVD risk in insulin-resistant populations. Additional research is needed to determine the best pathways to mitigate PCOS-associated CVD risk.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperandrogenism; Male; Polycystic Ovary Syndrome; Risk Factors; Stroke
PubMed: 35512976
DOI: 10.1016/j.fertnstert.2022.03.009 -
Journal of Healthcare Engineering 2022The polycystic ovary syndrome (PCOS) is the disease featured by elevated levels of androgens, ovulatory dysfunction, and morphological abnormalities. At reproductive... (Review)
Review
The polycystic ovary syndrome (PCOS) is the disease featured by elevated levels of androgens, ovulatory dysfunction, and morphological abnormalities. At reproductive stage of women, the rate of PCOS occurrence is measured as 6-10% and the prevalence rate may be double. There are different pathophysiological factors involved in PCOS, and they play a major role in various abnormalities in individual patient. It is clear that there is noteworthy elevation of androgen in PCOS, causing substantial misery and infertility problems. The overexposure of androgen is directly linked with insulin resistance and hyperinsulinaemia. It has been reported previously that PCOS is related to cardiac metabolic miseries and potently increases the risk of heart diseases. Endometrial cancer is also a serious concern which is reported with exceedingly high incidence in women with PCOS. However, the overexposure of androgen has direct and specific influence on the development of insulin resistance. Although many factors are involved, resistance to the insulin and enhanced level of androgen are considered the major causes of PCOS. In the present review, we have focused on the pathophysiology and major revolutions of insulin resistance and excessive levels of androgen in females with PCOS.
Topics: Androgens; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 35356614
DOI: 10.1155/2022/9240569 -
The Journal of Clinical Endocrinology... Feb 2022Although polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, risk factors that may cause the syndrome are poorly... (Review)
Review
CONTEXT
Although polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, risk factors that may cause the syndrome are poorly understood. Based on epidemiologic studies, PCOS is thought to cause several adverse outcomes such as cardiovascular disease; however, the common presence of comorbidities such as obesity may be responsible for such associations, rather than PCOS in and of itself. To overcome the limitations of observational studies, investigators have employed Mendelian randomization (MR), which uses genetic variants to interrogate causality between exposures and outcomes.
EVIDENCE ACQUISITION
To clarify causes and consequences of PCOS, this review will describe MR studies involving PCOS, both as an exposure and as an outcome. The literature was searched using the terms "Mendelian randomization," "polycystic ovary syndrome," "polycystic ovarian syndrome," and "PCOS" (to May 2021).
EVIDENCE SYNTHESIS
MR studies have suggested that obesity, testosterone levels, fasting insulin, serum sex hormone-binding globulin concentrations, menopause timing, male-pattern balding, and depression may play a causal role in PCOS. In turn, PCOS may increase the risk of estrogen receptor-positive breast cancer, decrease the risk of endometrioid ovarian cancer, and have no direct causal effect on type 2 diabetes, coronary heart disease, or stroke.
CONCLUSIONS
The accumulation of genome-wide association studies in PCOS has enabled multiple MR analyses identifying factors that may cause PCOS or be caused by PCOS. This knowledge will be critical to future development of measures to prevent PCOS in girls at risk as well as prevent complications in those who have PCOS.
Topics: Breast Neoplasms; Causality; Depression; Female; Genetic Predisposition to Disease; Humans; Mendelian Randomization Analysis; Ovarian Neoplasms; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 34669940
DOI: 10.1210/clinem/dgab757 -
International Journal of Molecular... Apr 2022Polycystic ovary syndrome (PCOS) is a heterogeneous and extremely common disease with symptoms that vary with the age of the patient, typically characterized by... (Review)
Review
Polycystic ovary syndrome (PCOS) is a heterogeneous and extremely common disease with symptoms that vary with the age of the patient, typically characterized by hyperandrogenism, chronic oligo-anovulation, and/or several metabolic disorders. The syndrome includes various phenotypes, and the pathogenesis is multifactorial, often involving insulin resistance. This feature is closely related to ovarian dysfunction, inflammation, hyperandrogenism, and metabolic disorders, which characterize and complicate the syndrome. Therapy currently considers both lifestyle improvements and medications, and must be tailored on a case-by-case basis. To date, the published studies have not arrived at a definition of the most suitable therapy for each individual case and many of the drugs used are still off-label. In this review, we discuss some controversial diagnostic and therapeutic aspects of PCOS, such as the role of insulin resistance, inflammation, and hyperandrogenism. We also evaluated the advantages and disadvantages of contraceptive therapy and antiandrogens.
Topics: Female; Humans; Hyperandrogenism; Inflammation; Insulin Resistance; Male; Metabolic Diseases; Polycystic Ovary Syndrome
PubMed: 35456928
DOI: 10.3390/ijms23084110 -
Oncology Reports Apr 2022Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinum‑based chemotherapy is as high... (Review)
Review
Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinum‑based chemotherapy is as high as 80%, but in most advanced patients, final relapse and death are caused by acquired drug resistance. The development of resistance to therapy in ovarian cancer is a significant hindrance to therapeutic efficacy. The resistance of ovarian cancer cells to chemotherapeutic mechanisms is rather complex and includes multidrug resistance, DNA damage repair, cell metabolism, oxidative stress, cell cycle regulation, cancer stem cells, immunity, apoptotic pathways, autophagy and abnormal signaling pathways. The present review provided an update of recent developments in our understanding of the mechanisms of ovarian cancer platinum‑based chemotherapy resistance, discussed current and emerging approaches for targeting these patients and presented challenges associated with these approaches, with a focus on development and overcoming resistance.
Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Cisplatin; Drug Resistance, Neoplasm; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 35211759
DOI: 10.3892/or.2022.8293 -
Endocrine Reviews Jul 2020More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite... (Review)
Review
More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.
Topics: Animals; Disease Models, Animal; Female; Humans; Polycystic Ovary Syndrome
PubMed: 32310267
DOI: 10.1210/endrev/bnaa010 -
Revista Medica Del Instituto Mexicano... Aug 2022During folliculogenesis, different proinflammatory cytokines have a physiological role in the weakening of the follicle wall and an eventual rupture at ovulation.... (Review)
Review
During folliculogenesis, different proinflammatory cytokines have a physiological role in the weakening of the follicle wall and an eventual rupture at ovulation. Chronic inflammation is closely related to endothelial dysfunction, cardiovascular disease, coronary artery disease, and polycystic ovary syndrome. Polycystic ovary syndrome is characterized by androgen excess and ovarian dysfunction. Emerging evidence suggests that the long-term metabolic effects and cardiovascular complications observed in this syndrome may be related to the presence of a mild chronic inflammatory state. It is unclear whether androgen excess promotes an inflammatory state or, conversely, whether inflammatory molecules stimulate androgen production. Early detection of risk factors will help in the prevention and control of cardiovascular diseases, since the metabolic alterations associated with this syndrome can predispose to worse cardiovascular health outcomes.
Topics: Androgens; Cardiovascular Diseases; Cytokines; Female; Humans; Inflammation; Ovarian Follicle; Polycystic Ovary Syndrome
PubMed: 36049035
DOI: No ID Found