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Adolescent polycystic ovary syndrome according to the international evidence-based guideline
Background
Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging because features of normal pubertal development overlap with adult diagnostic criteria. The international evidence-based PCOS Guideline aimed to promote accurate and timely diagnosis, to optimise consistent care, and to improve health outcomes for adolescents and women with PCOS.
Methods
International healthcare professionals, evidence synthesis teams and consumers informed the priorities, reviewed published data and synthesised the recommendations for the Guideline. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied to appraise the evidence quality and the feasibility, acceptability, cost, implementation and strength of the recommendations.
Results
This paper focuses on the specific adolescent PCOS Guideline recommendations. Specific criteria to improve diagnostic accuracy and avoid over diagnosis include: (1) irregular menstrual cycles defined according to years post-menarche; > 90 days for any one cycle (> 1 year post-menarche), cycles 45 days (> 1 to  35 days (> 3 years post-menarche) and primary amenorrhea by age 15 or > 3 years post-thelarche. Irregular menstrual cycles (< 1 year post-menarche) represent normal pubertal transition. (2) Hyperandrogenism defined as hirsutism, severe acne and/or biochemical hyperandrogenaemia confirmed using validated high-quality assays. (3) Pelvic ultrasound not recommended for diagnosis of PCOS within 8 years post menarche. (4) Anti-Müllerian hormone levels not recommended for PCOS diagnosis; and (5) exclusion of other disorders that mimic PCOS. For adolescents who have features of PCOS but do not meet diagnostic criteria an ‘at risk’ label can be considered with appropriate symptomatic treatment and regular re-evaluations. Menstrual cycle re-evaluation can occur over 3 years post menarche and where only menstrual irregularity or hyperandrogenism are present initially, evaluation with ultrasound can occur after 8 years post menarche. Screening for anxiety and depression is required and assessment of eating disorders warrants consideration. Available data endorse the benefits of healthy lifestyle interventions to prevent excess weight gain and should be recommended. For symptom management, the combined oral contraceptive pill and/or metformin may be beneficial.
Conclusions
Extensive international engagement accompanied by rigorous processes honed both diagnostic criteria and treatment recommendations for PCOS during adolescence
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
Prevalence of polycystic ovary syndrome in young women from North India: A Community-based study
Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Due to the logistics of diagnosis and lack of consensus on the diagnostic criteria, there are very few prevalence studies in the community. This study was aimed to assess the prevalence of PCOS in women 18-25 years of age, conducted in college girls from Lucknow, North India. Materials and Methods: Sample size for the study was calculated as 1052. Girls from 3 different colleges were approached (n = 2150), 1520 (70.7%) agreed to participate. They were asked to fill up a questionnaire asking details of menstrual cycle and features of hyperandrogenism. Hirsutism was self-reported. Responses were verified by a trained research assistant. A probable case was defined as a girl with menstrual irregularity (MI) or hirsutism (H) or both. All the probable cases were invited for detailed examination, hormone estimation, and ovarian ultrasonography. Results: Of the 1520 girls, 200 (13.1%) were labeled as probable cases; 175 (87.5%) had MI and 25 (12.5%) had both MI and H. Of the 200 cases, 75 (37.5%) had hormonal evaluation while 11 agreed for ultrasonography. 27 girls had confirmed PCOS. Therefore, if all the 200 girls would have had hormonal evaluation, 56 girls were likely to be confirmed as PCOS, giving a calculated prevalence of 3.7% (95% CI, 2.6-4.4) in this population. The mean age of these PCOS cases was 18.96 ± 1.73 yrs, body mass index was 21.72 ± 5.48 Kg/m 2 , and waist hip ratio was 0.81 ± 0.08. Only 12% girls had a body mass index ≥ 27.5 Kg/m 2 , but 44% had waist hip ratio > 0.81, again highlighting that despite low BMI, Indians have more abdominal obesity. Conclusion: Calculated prevalence of PCOS in women between the ages of 18-25 years from Lucknow, north India, is 3.7%. Majority of these girls were lean but have abdominal obesity
Familial clustering of metabolic phenotype in brothers of women with polycystic ovary syndrome
Kocher-Debre-Semelaigne syndrome with arrhythmogenic right ventricular cardiomyopathy: A hitherto unrecognized association
Kocher-Debre-Semelaigne (KDS) syndrome is a rare form of hypothyroid myopathy, with associated hypertrophy of muscles. Although cardiac manifestations of hypothyroidism are well known, reports of cardiac involvement in KDS have only described the occurrence of pericardial effusion as an association. This report describes an adolescent male presenting with typical features of this rare syndrome along with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), an association not yet described in the literature
Juvenile granulosa cell tumor presenting as isosexual precocious puberty: A case report and review of literature
The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case report documents a rare cause of isosexual precocious puberty, a juvenile granulosa cell tumor of the ovary-and a brief literature review. A 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Abdominal ultrasound revealed a mass in the right adnexa. Other causes of precocious puberty were excluded. Elective surgery was planned, but the patient presented to the emergency room with torsion of ovary. She underwent an exploratory laparotomy for tumor resection and right salpingo oophorectomy. Pathology reported a juvenile granulosa cell tumor of the ovary. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. Early stage disease has good prognosis. Adjuvant chemotherapy is not indicated in this setting
Managing disorder of sexual development surgically: A single center experience
Introduction: Ambiguous genitalia are a major cause of parental anxiety and create psychological and social problems to patient, if not managed properly. Here we present our experience in managing patients with ambiguous genitalia.
Material and Methods: We retrospectively reviewed clinical records of all patients with ambiguous genitalia managed surgically at out institute between December 1989 and January 2011. Relevant history, clinical examination , investigations and surgical procedures performed were analyzed and results were evaluated in terms of anatomical, functional and psychosexual outcomes.
Results: Female pseudohermaphroditism was the most common cause of genital ambiguity in our patients. Male and female genitoplasty was done according to gender of rearing, genital anatomy and parental choice. Twenty six patients (86.6%) reported satisfactory cosmetic outcome and 22 (73.3%) satisfactory functional outcome on long term follow-up. Among the 24 patients diagnosed as male pseudohermaphroditism 14 (82.3%) patient have reported satisfactory cosmetic outcome and 13 (76.4%) have reported satisfactory functional outcome. In patients with mixed gonadal dysgenesis and true hermaphroditism satisfactory cosmetic and functional outcome was seen in 70% patient.
Conclusion: Managing patients of genital ambiguity according to gender of rearing, genital anatomy and parental choice carries good prognosis in terms of anatomical, functional and psychosexual outcome
β cell function and insulin resistance in lean cases with polycystic ovary syndrome
<p>Obesity is a major factor in development of insulin resistance (IR) and metabolic features in polycystic ovary syndrome (PCOS) patients. Nearly two-thirds patients with PCOS (30 of 37 confirmed cases of PCOS) in our previous community based study were lean, in contrast to Caucasians. Metabolic parameters including IR and β cell function have not been characterized well in this group of lean PCOS. To study the metabolic features including IR and β cell function in lean PCOS patients, 53 patients with BMI, <23 kg/m<sup>2</sup> were compared with 71 obese PCOS and 45 age and body mass index matched controls. Lean patients had similar β cell function and IR as compared to controls and obese patients, though the latter group had more metabolic abnormality. Fasting c-peptide and its ratio to glucose were significantly higher in lean patients compared to controls. In subset of subjects with five point OGTT, disposition index and Matsuda index (MI) showed significant negative correlation with BMI and blood pressure. MI also negatively correlated with waist, WHR, and HOMAB. High fasting C-peptide is probably a class effect as is seen in both lean and obese PCOS.</p