The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion of PPAR-γ

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome

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

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rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated.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

Ovarian And Adipose Tissue Dysfunction In Polycystic Ovary Syndrome: Report Of The 4Th Special Scientific Meeting Of The Androgen Excess And Pcos Society

Significant advances have been made in our understanding of ovarian dysfunction in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function are likely to play an important role in its pathophysiology. This review highlights the principal novel concepts presented at the 4th special scientific meeting of the Androgen Excess and PCOS Society, "Ovarian and Adipose Tissue Dysfunction: Potential Roles in Polycystic Ovary Syndrome," which occurred on June 6, 2008 in San Francisco, California. (Fertil Steril (R) 2010;94:690-3. (C) 2010 by American Society for Reproductive Medicine.)Wo

Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose Load in Lean Women with Severe Acne Normalizes After Isotretinoin Treatment

Background/Aim: Isotretinoin, the drug of choice for severe acne, might be associated with a decrease in insulin sensitivity. Adiponectin is an adipose tissue-derived protein that increases insulin sensitivity. In this study, we aimed to investigate adiponectin levels in postadolescent severe acne and the effect of isotretinoin on adiponectin levels. Methods: Participants included 18 female patients with severe acne and 18 healthy women matched for age and body mass index (BMI). Acne patients completed a 6-month isotretinoin treatment. Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed in healthy women once and in patients with acne before and after treatment. Results: At baseline, patients with acne had significantly lower serum adiponectin levels than controls. Isotretinoin treatment resulted in a significant increase in weight, BMI, and triglyceride and adiponectin levels. Glucose metabolism markers in patients with acne and controls were similar at baseline and did not change after treatment. Baseline OGTT in acne patients revealed an increased adiponectin response at 2 h, which was not present in healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne patients was diminished after isotretinoin treatment. Conclusion: Adiponectin levels are differently regulated in women with severe acne and healthy controls in that circulating basal levels in patients are suppressed and show an increase in response to oral glucose load. Suppression of baseline adiponectin ameliorates after 6 months of isotretinoin treatment, reaching levels similar to those of healthy controls. (C) 2017 S. Karger AG, BaselWoSScopu