BACKGROUND Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age, yet debate over appropriate diagnostic criteria and design limitations ...with sampling methodology have left some doubt as to the actual prevalence in the community. The objective of this study was to create a representative prevalence estimate of PCOS in the community under the National Institutes of Health (NIH) criteria and the more recent Rotterdam consensus criteria and Androgen Excess Society (AES) criteria. METHODS A retrospective birth cohort study was carried out in which 728 women born during 1973–1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27–34 year; n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed. RESULTS The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 ± 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 ± 2.4% which increased to 17.8 ± 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 ± 2.2%, and 12.0 ± 2.4% with the imputed data. Of the women with PCOS, 68–69% did not have a pre-existing diagnosis. CONCLUSIONS The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.
Summary
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rigorous evidence‐based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated.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 (GDGs), 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: (a) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (b) reducing unnecessary testing; (c) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (d) 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.
Polycystic Ovary Syndrome (PCOS) is common among females, with significant metabolic and reproductive comorbidities. We describe PCOS development in a pediatric population.
We assessed ...cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS.
Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 0.99 vs 0.30 1.04; 3.5 kg 2.6 vs 2.7 1.5), early teen (0.88 1.01 vs 0.25 1.08; 9.4 kg 6.7 vs 6.1 3.4), and midteen (0.78 1.03 vs 0.33 0.97; 11.6 kg 7.2 vs 9.1 4.9) visits as well as lower adiponectin to leptin ratio at the early (0.65 0.69 vs 1.04 0.97) and midteen (0.33 0.26 vs 0.75 1.21) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio OR 1.42; 95% confidence interval CI 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58).
Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk.
Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria ...are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes. We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS.
Using biochemical and genotype data from a previously published PCOS genome-wide association study (GWAS), we investigated whether there were reproducible phenotypic subtypes of PCOS with subtype-specific genetic associations. Unsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped cohort of 893 PCOS cases (median and interquartile range IQR: age = 28 25-32, body mass index BMI = 35.4 28.2-41.5). The clusters were replicated in an independent, ungenotyped cohort of 263 PCOS cases (median and IQR: age = 28 24-33, BMI = 35.7 28.4-42.3). The clustering revealed 2 distinct PCOS subtypes: a "reproductive" group (21%-23%), characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low BMI and insulin levels, and a "metabolic" group (37%-39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels. We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes. We identified alleles in 4 loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN, P = 2.2 × 10-10; IQCA1, P = 2.8 × 10-9; BMPR1B/UNC5C, P = 9.7 × 10-9; CDH10, P = 1.2 × 10-8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P = 1.0 × 10-8). We developed a predictive model to classify a separate, family-based cohort of 73 women with PCOS (median and IQR: age = 28 25-33, BMI = 34.3 27.8-42.3) and found that the subtypes tended to cluster in families and that carriers of previously reported rare variants in DENND1A, a gene that regulates androgen biosynthesis, were significantly more likely to have the reproductive subtype of PCOS. Limitations of our study were that only PCOS cases of European ancestry diagnosed by National Institutes of Health (NIH) criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated.
In conclusion, we have found reproducible reproductive and metabolic subtypes of PCOS. Furthermore, these subtypes were associated with novel, to our knowledge, susceptibility loci. Our results suggest that these subtypes are biologically relevant because they appear to have distinct genetic architecture. This study demonstrates how phenotypic subtyping can be used to gain additional insights from GWAS data.
STUDY QUESTION
What is the prevalence, phenotype and metabolic features of polycystic ovary syndrome (PCOS) in the same population according to three different diagnostic criteria?
SUMMARY ANSWER
The ...prevalence of PCOS under National Institutes of Health (NIH), Rotterdam and Androgen Excess and PCOS (AE-PCOS) Society criteria was 6.1, 19.9 and 15.3%, respectively. PCOS carried a 2-fold increased risk of metabolic syndrome regardless of the diagnostic criteria used.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
The prevalence rates of PCOS differ depending on the diagnostic criteria used to define the syndrome. The current paper gives the prevalence rates of the component and composite phenotypes of PCOS in the same population and reports similar rates of metabolic syndrome in women with PCOS under contrasting diagnostic criteria.
DESIGN
In this cross-sectional study, 392 women between the ages of 18 and 45 years were analyzed.
PARTICIPANTS AND SETTING
When the prevalence of PCOS according to NIH was set to 8% with a precision of 2.2% and confidence interval of 95%, the sample size required for a prevalence survey was found to be 400 subjects. The study was carried out in the General Directorate of Mineral Research and Exploration, a government-based institute, in which the largest number of female staff (n = 527) are employed within a single institute in Ankara, Turkey. The study was performed between 7 December 2009 and 30 April 2010. All female subjects between the ages of 18 and 45 years were invited to participate. Women older than 45 or younger than 18 years, post-menopausal women, women with a history of hysterectomy or bilateral oopherectomy and pregnant women were excluded. Totally, 392 of the employees were recruited for the final analyses.
MAIN RESULTS AND THE ROLE OF CHANCE
The prevalence of PCOS under NIH, Rotterdam and AE-PCOS Society criteria were 6.1, 19.9 and 15.3%, respectively. While the prevalence of metabolic syndrome was 6.1% in the whole study group, within the patients diagnosed as PCOS according to NIH, Rotterdam and AE-PCOS Society criteria, it was 12.5, 10.3 and 10.0%, respectively.
BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION
Even though we have included women working at a single institution with a high response rate for the participation, we cannot exclude potential selection bias due to undetermined differences between our sample and background community. We might have underestimated actual prevalence of metabolic syndrome in PCOS due to lack of oral glucose tolerance test 2 h glucose data.
GENERALIZABILITY TO OTHER POPULATIONS
Current results can be generalized to Caucasian populations and may present variations in other populations according to race and ethnicity.
STUDY FUNDING/COMPETING INTEREST(S)
This work was, in part, sponsored by Merck Serono.
TRIAL REGISTRATION NUMBER
Not applicable.
STUDY QUESTION
What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)?
...SUMMARY ANSWER
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively.
WHAT IS KNOWN ALREADY?
The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS.
STUDY DESIGN, SIZE, DURATION
From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20–40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark.
PARTICIPANTS/MATERIAL, SETTING, METHODS
We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2–5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured.
MAIN RESULTS AND THE ROLE OF CHANCE
The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women < 30 years to 14.7% in women aged 30–34 years, and 10.2% in women ≥ 35 years (P < 0.001). In total, 53.5% fulfilled the criterion for polycystic ovaries with a significant age-related decrease from 69.0% in women < 30 years to 55.8% in women aged 30–34 years, and 42.8% in women ≥ 35 years (P < 0.001). AMH or age-adjusted AMH Z-score was found to be a reliable marker of polycystic ovaries in women with PCOS according to the Rotterdam criteria area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990–0.999 and AUC 0.992 (95% CI: 0.987–0.998), respectively, and an AMH cut-off value of 18 pmol/l and AMH Z-score of −0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and 97.9%, respectively). In total, AFC > 19 or AMH > 35 occurred in 17.7 and 23.0%, respectively. The occurrence of AFC > 19 or AMH > 35 in the age groups < 30, 30–34 and ≥ 35 years was 31.0 and 35.7%, 18.8 and 21.3%, and 9.6 and 18.7%, respectively. When replacing the Rotterdam criterion for polycystic ovaries by AFC > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 or 8.5%, respectively, and in the age groups < 30, 30–34 and ≥ 35 years, the prevalences were 17.9 and 22.6%, 3.6 and 5.6%, and 3.6 and 4.8%, respectively.
LIMITATIONS, REASON FOR CAUTION
The participants of the study were all health-care workers, which may be a source of selection bias. Furthermore, the exclusion of hormonal contraceptive users from the study population may have biased the results, potentially excluding women with symptoms of PCOS.
WIDER IMPLICATIONS OF THE FINDINGS
AMH may be used as a marker of polycystic ovaries in PCOS. However, future studies are needed to validate AMH threshold levels, and AMH Z-score may be appropriate to adjust for the age-related decline in the AFC.
STUDY FUNDING/COMPETING INTEREST(S)
None.
TRIAL REGISTRATION NUMBER
Not applicable.
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.
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.
Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) ...biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.
Background
Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian dysfunction, ...hyperandrogenaemia, infertility, hormonal imbalance and chronic anovulation. Experimental evidence infers that PCOS women are prone to cardiovascular problems and insulin resistance.
Purpose
To furnish the details about the association of inflammatory markers in PCOS.
Design
An extensive literature search on PubMed, science direct and google scholar has been performed for articles about PCOS and inflammation in PCOS. A comprehensive analysis using original articles, reviews, systemic and meta-analysis was conducted for better understanding the relationship between inflammatory cytokines and PCOS.
Results
The inflammatory markers perform a substantial part in managing the functions of the ovary. Any disturbances in their levels can lead to ovarian dysfunction. Inflammatory markers are associated with PCOS pathogenesis. The interplay between inflammatory cytokines in the PCOS ovary strongly implies that inflammation is one of the most potent risk factors of PCOS.
Conclusion
Inflammatory markers have a significant role in regulating the ovary. This manuscript highlights the significance of metabolic and inflammatory markers with PCOS. Since PCOS is always considered as a metabolic disorder, researchers can also consider focusing on the relationship between the inflammatory markers in PCOS to establish a new treatment or management of the disease and to improve women's health.
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