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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 -
Current Nutrition Reports Sep 2023Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age worldwide. This disease causes menstrual, metabolic,... (Review)
Review
PURPOSE OF REVIEW
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age worldwide. This disease causes menstrual, metabolic, and biochemical abnormalities such as hyperandrogenism, oligo-anovulatory menstrual cycles, polycystic ovary, hyperleptinemia, insulin resistance (IR), and cardiometabolic disorders, often associated with overweight or obesity and visceral adiposity.
RECENT FINDINGS
The etiology and pathophysiology of PCOS are not yet fully understood, but insulin seems to play a key role in this disease. PCOS shares an inflammatory state with other chronic diseases such as obesity, type II diabetes, and cardiovascular diseases; however, recent studies have shown that a healthy nutritional approach can improve IR and metabolic and reproductive functions, representing a valid therapeutic strategy to ameliorate PCOS symptomatology. This review aimed to summarize and collect evidence about different nutritional approaches such as the Mediterranean diet (MedDiet) and the ketogenic diet (KD), as well as bariatric surgery and nutraceutical supplementation as probiotics, prebiotics, and synbiotics, among the others, used in patients with PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Diabetes Mellitus, Type 2; Hyperandrogenism; Obesity; Insulin Resistance
PubMed: 37213054
DOI: 10.1007/s13668-023-00479-8 -
Circulation Dec 2023Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common...
BACKGROUND
Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, is associated with an increased prevalence and extent of coronary artery disease. However, the mechanism through which PCOS affects cardiac health in women remains unclear.
METHODS
Prenatal anti-Müllerian hormone treatment or peripubertal letrozole infusion was used to establish mouse models of PCOS. RNA sequencing was performed to determine global transcriptomic changes in the hearts of PCOS mice. Flow cytometry and immunofluorescence staining were performed to detect myocardial macrophage accumulation in multiple PCOS models. Parabiosis models, cell-tracking experiments, and in vivo gene silencing approaches were used to explore the mechanisms underlying increased macrophage infiltration in PCOS mouse hearts. Permanent coronary ligation was performed to establish myocardial infarction (MI). Histologic analysis and small-animal imaging modalities (eg, magnetic resonance imaging and echocardiography) were performed to evaluate the effects of PCOS on injury after MI. Women with PCOS and control participants (n=200) were recruited to confirm findings observed in animal models.
RESULTS
Transcriptomic profiling and immunostaining revealed that hearts from PCOS mice were characterized by increased macrophage accumulation. Parabiosis studies revealed that monocyte-derived macrophages were significantly increased in the hearts of PCOS mice because of enhanced circulating Ly6C monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic Ly6C monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Plasma norepinephrine (a sympathetic neurotransmitter) levels and spleen size were consistently increased in women with PCOS when compared with those in control participants, and norepinephrine levels were significantly correlated with circulating CD14CD16 monocyte counts. Compared with animals without PCOS, PCOS animals showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional silencing in PCOS mice significantly suppressed cardiac inflammation and improved cardiac injury after MI.
CONCLUSIONS
Our data documented previously unrecognized mechanisms through which PCOS could affect cardiovascular health in women. PCOS may promote myocardial macrophage accumulation and post-MI cardiac remodeling because of augmented splenic myelopoiesis.
Topics: Pregnancy; Female; Humans; Mice; Animals; Polycystic Ovary Syndrome; Ventricular Remodeling; Myocardial Infarction; Heart Injuries; Inflammation; Norepinephrine
PubMed: 37937441
DOI: 10.1161/CIRCULATIONAHA.123.065827 -
International Journal of Molecular... Jun 2023Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive... (Review)
Review
Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women.
Topics: Pregnancy; Female; Humans; Adult; Reproduction; Thyroid Hormones; Thyroid Diseases; Polycystic Ovary Syndrome
PubMed: 37372963
DOI: 10.3390/ijms24129815 -
JAMA Oncology Sep 2023The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease.
OBJECTIVE
To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months.
INTERVENTIONS
Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/μL [to convert to ×109/μL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy.
MAIN OUTCOMES AND MEASUREMENTS
The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population.
RESULTS
A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events.
CONCLUSION AND RELEVANCE
This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03709316.
Topics: Humans; Female; Middle Aged; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Progression-Free Survival; Indazoles; Double-Blind Method; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37440217
DOI: 10.1001/jamaoncol.2023.2283 -
Frontiers in Endocrinology 2023Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing. (Review)
Review
BACKGROUND
Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing.
OBJECTIVE
To comprehensively review data available in the literature regarding the relationship between PCOS and the thyroid function, and its abnormalities.
METHODS
Nine main areas of interest were identified and analyzed according to the available evidence: 1) Evaluation of thyroid function for PCOS diagnosis; 2) Epidemiology data on thyroid function/disorders in patients with PCOS, and vice versa; 3) Experimental data supporting the relationship between thyroid function/disorders and PCOS; 4) Effects of thyroid function/disorders on PCOS features, and vice versa; 5) Effect of thyroid alterations on the cardiometabolic risk in women with PCOS; 6) Effect of thyroid abnormalities on reproductive outcomes in women with PCOS; 7) Relationship between thyroid function/abnormalities in patients with PCOS who are undergoing fertility treatment; 8) Effect of treatments for thyroid diseases on PCOS; and 9) Effect of treatments for PCOS on thyroid function. An extensive literature search for specific keywords was performed for articles published from 1970 to March 2023 using PubMed and Web of Science. Data were reported in a narrative fashion.
RESULTS
PCOS is a diagnosis of exclusion for which diagnosis is possible only after excluding disorders that mimic the PCOS phenotype, including thyroid dysfunctions. However, the tests and the cutoff values used for this are not specified. Many experimental and clinical data suggest a relationship between perturbations of the thyroid function and PCOS. Direct and unequivocal evidence on the effects of thyroid function/disorders on PCOS features are lacking. High thyroid-stimulating hormone levels and subclinical hypothyroidism may be associated with significant worsening of several intermediate endpoints of cardiometabolic risk in women with PCOS. Thyroid abnormalities may worsen reproductive outcomes, especially in patients undergoing fertility treatment. To date, there are no data demonstrating the efficacy of thyroid medications on fertility and cardiometabolic risk in women with PCOS. Lifestyle modification changes, metformin, and vitamin D seem to improve thyroid function in the general population.
CONCLUSION
PCOS and thyroid disorders are closely related, and their coexistence may identify patients with a higher reproductive and metabolic risk. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.
Topics: Female; Humans; Pregnancy; Polycystic Ovary Syndrome; Thyroid Diseases; Hypothyroidism; Thyroid Dysgenesis; Antibodies; Cardiovascular Diseases
PubMed: 37635968
DOI: 10.3389/fendo.2023.1251866 -
Frontiers in Immunology 2023Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha... (Review)
Review
Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.
Topics: Female; Humans; Folate Receptor 1; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Antibodies, Monoclonal; Eye
PubMed: 37711615
DOI: 10.3389/fimmu.2023.1254532 -
Frontiers in Endocrinology 2023Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility... (Review)
Review
Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways.
Topics: Rats; Humans; Female; Animals; Exosomes; Primary Ovarian Insufficiency; Menopause, Premature; Antineoplastic Agents
PubMed: 37564988
DOI: 10.3389/fendo.2023.1205901 -
International Journal of Gynecological... Sep 2023Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly...
Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.
Topics: Humans; Female; Consensus; Quality of Life; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Ovarian Neoplasms
PubMed: 37591609
DOI: 10.1136/ijgc-2023-004610 -
Human Reproduction (Oxford, England) 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 remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.
WIDER IMPLICATIONS OF THE FINDINGS
The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program.
STUDY FUNDING/COMPETING INTEREST(S)
This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
Topics: Pregnancy; Adult; Female; Humans; Child; Polycystic Ovary Syndrome; Quality of Life; Australia; Risk Factors; Gynecology
PubMed: 37580037
DOI: 10.1093/humrep/dead156