Polycystic ovary syndrome (PCOS) is a highly prevalent disorder effecting reproductive-aged women worldwide. This article addresses the evolution of the criteria used to diagnosis PCOS; reviews ...recent advances in the phenotypic approach, specifically in the context of the extended Rotterdam criteria; discusses limitations of the current criteria used to diagnosis, particularly when studying adolescents and women in the peri- and postmenopause; and describes significant strides made in understanding the epidemiology of PCOS. This review recognizes that although there is a high prevalence of PCOS, there is increased variability when using Rotterdam 2003 criteria, owing to limitations in population sampling and approaches used to define PCOS phenotypes. Last, we discuss the distribution of PCOS phenotypes, their morbidity, and the role that referral bias plays in the epidemiology of this syndrome.
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made ...in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and is characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Obesity, low-grade chronic ...inflammatory status, and insulin-resistance (IR) often coexist in PCOS. The Mediterranean diet (MD) is an anti-inflammatory dietary pattern, which is rich in complex carbohydrates and fiber, and high in monounsaturated fat. There is a close association among obesity, low-grade chronic inflammation, IR, and hormonal derangements in PCOS. The main aim of the present study was to evaluate the adherence to MD, the dietary intake, and the body composition and their association with PCOS clinical severity in a cohort of treatment-naïve women with PCOS when compared with a control group of healthy women matched for age and body mass index (BMI). In this case-controlled, cross-sectional study, we enrolled 112 patients with PCOS and 112 controls. PREvención con DIetaMEDiterránea (PREDIMED) and seven-day food records were used to evaluate the degree of adherence to the MD and dietary pattern, respectively. Body composition was evaluated by bioelectrical impedance analysis (BIA) phase-sensitive system. Testosterone levels and Ferriman-Gallwey score assessed the clinical severity of PCOS. C-reactive protein (CRP) levels were determined with a nephelometric assay with CardioPhase high sensitivity. PCOS women showed higher testosterone levels, Ferriman-Gallwey score, fasting insulin and glucose levels, and Homeostatic Model Assessment (HoMA)-IR when compared with the control group (
< 0.001). In addition, we found that the PCOS women consumed less extra-virgin olive oil, legumes, fish/seafood, and nuts compared with control group. Despite no differences in energy intake between the two groups, the PCOS women consumed a lower quantity of complex carbohydrate, fiber, monounsaturated fatty acids (MUFA), and n-3 polyunsaturated fatty acid (PUFA), and higher quantity of simple carbohydrate, total fat, saturated fatty acid (SFA), PUFA and n-6 PUFA than the control group. The PCOS women have an adverse body composition when compared with controls, with the lowest values of phase angle (PhA) and fat-free mass (
< 0.001). Additionally, after adjusting for BMI and total energy intake, testosterone levels showed significant negative correlations with PREDIMED score (
< 0.001) and consumption of protein (
= 0.005), complex carbohydrate (
< 0.001), fiber (
< 0.001), MUFA (
< 0.001), n-3 PUFA (
= 0.001), and positive associations with CRP levels, simple carbohydrate, SFA, n-6 PUFA (
< 0.001, respectively), and PUFA (
= 0.002). The cut-off for PREDIMED score ≤ 6 (
< 0.001, area under the curve (AUC) 0.848, standard error 0.036, 95% confidence interval (CI) 0.768 to 0.909) could serve as a threshold for significantly increased risk of high value of testosterone levels. In conclusion, a novel direct association between the adherence to MD and the clinical severity of the disease was reported in women with PCOS. This association could support a therapeutic role of foods and nutrients of the Mediterranean dietary pattern in the PCOS pathogenesis likely involving their inflammatory status, IR, and hyperandrogenemia. In addition, we reported a different body composition that is characterized by lower PhA and fat-free mass than controls. These data suggested a role of PhA as a useful marker of the clinical severity of this syndrome and provided strong evidence regarding the strategic relevance of the nutritional assessment in the management of women with PCOS.
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor ...understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by ...hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed.
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?
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.
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.
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.
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.
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.
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.
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.
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.
To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and ...future research.
Literature review and expert consensus.
Professional society.
None.
None.
A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS.
The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence.
Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.
How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control ...study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F
) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F
-F
offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F
-F
offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
Abstract
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.
Graphical Abstract
Graphical Abstract
Insulin and the polycystic ovary syndrome Macut, Djuro; Bjekić-Macut, Jelica; Rahelić, Dario ...
Diabetes research and clinical practice,
08/2017, Letnik:
130
Journal Article
Recenzirano
Abstract Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged ...adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes. PCOS women show age-related existence of hypertension, and subtle endothelial and vascular changes. Adverse reproductive outcomes include anovulatory infertility, and unrecognised potentiation of the hormone-dependent endometrial cancer. The main therapeutic approach is lifestyle modification. Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment. Thiazolidinediones should be reserved for women intolerant of or refractory to metformin, while GLP1 has a potential therapeutic use in obese PCOS women. Randomised clinical trials and repetitive studies on different PCOS phenotypes for the preventive actions and therapeutic options are still lacking, though.
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