Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

Polycystic Ovary Syndrome in Adolescence.

Polycystic ovary syndrome (PCOS) is a common, complex, and chronic condition that presents many diagnostic and management challenges for managing clinicians. PCOS diagnosis in adolescents presents a particular challenge for treating clinicians due to the overlap of diagnostic features with normal physiological changes during adolescence. Adolescent diagnostic criteria include well-defined menstrual irregularity according to time postmenarche and hyperandrogenism, but does not require the use of pelvic ultrasound. Adolescents with only one criterion should be considered at risk of PCOS and be followed up around transition to adult care. While PCOS was traditionally considered to be a reproductive disorder, PCOS is now recognized to have major metabolic and cardiovascular health consequences and psychological sequelae that can be present from adolescence. Management of PCOS includes healthy lifestyle, metformin, combined oral contraceptive pill, and/or antiandrogens according to symptoms of concern even in adolescents at risk of PCOS.

Proteolytic activation of anti-Müllerian hormone is suppressed in adolescent girls.

PURPOSE: The ratio of the anti-Müllerian hormone (AMH) precursor (proAMH) to active AMH (AMHN,C) is higher in childhood than in adulthood but has never been quantified during adolescence. The ratio of proAMH to total AMH (AMH prohormone index, API) was examined during the puberty in healthy girls. The API was also compared between girls with and without polycystic ovary syndrome (PCOS) to determine if there were differences that could assist in PCOS diagnosis during adolescence. METHODS: Total AMH and proAMH were measured by immunoassay in a single-centre, cross-sectional observational study; 61 controls and 29 girls with PCOS were included in the study (age range 8-21 years). The API was calculated as proAMH as a percentage of total AMH. Differences in API between control and PCOS subjects and across age-groups were examined by Welch's ANOVA. The relationship between API and a range of metabolic parameters was examined by Pearson correlation. RESULTS: The API in healthy females increased between the ages of 10~15 years and declined from 15~20 years (p < 0.001). The API was negatively correlated with body mass index in the control (p = 0.04) and PCOS groups (p = 0.007). The API was associated with factors related to adiposity and lipid metabolism. The API was not significantly different in control girls and girls with PCOS. CONCLUSIONS: Higher API during adolescence suggests that proteolytic activation of proAMH is suppressed during this life stage. API was not different between control girls and girls with PCOS indicating that it is not useful in diagnosis of PCOS during adolescence.

Diagnosis experiences of adolescents with polycystic ovary syndrome: Cross-sectional study.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) report delayed diagnosis of the condition and receiving inadequate information at diagnosis. No studies have investigated the diagnosis experiences of adolescents with PCOS. Our objective was to investigate the adolescents' experiences of PCOS diagnosis and their concerns about the condition. DESIGN: Cross-sectional study. PATIENT(S): Eighty-six adolescents (aged 13-19 years) were diagnosed with PCOS by a medical practitioner. Adolescents were recruited consecutively from paediatric and women's outpatient hospital clinics in South Australia and online PCOS support organisations in Australia and the United Kingdom (May 2017-June 2019). MEASUREMENTS: PCOS diagnosis experience and information received at the time of diagnosis were evaluated using a validated questionnaire. RESULTS: The majority of the adolescents (n = 67, 78%) were diagnosed with PCOS in less than 1 year from their first doctor's visit but 11 (13%) were diagnosed more than 2 years from that visit. Fifty-three adolescents (66%) saw 1-2 health professionals before the diagnosis was made. Forty-nine adolescents (57%) were satisfied with the overall diagnosis experience but adolescents were either dissatisfied or reported that the information was not mentioned after diagnosis in relation to lifestyle management (n = 47, 55%), long-term complications (n = 53, 62%) and emotional support and counselling (n = 65, 76%). CONCLUSIONS: The majority of adolescent girls with PCOS are receiving a timely diagnosis, but delayed diagnosis still occurs in a minority of adolescents. Current information provided at diagnosis is not meeting the needs of adolescents and is a lost opportunity for preventive healthcare at a critical transition to adult care period.

Quality of life in adolescent girls with polycystic ovary syndrome.

Quality of life (QoL) is an important aspect of health and well-being. QoL is reduced in women with polycystic ovary syndrome (PCOS), but there is limited data in adolescents. This review aimed to assess studies regarding the QoL of adolescent girls with PCOS. Five databases were searched for relevant studies. Studies were included if they were conducted in adolescent girls with PCOS, aged 12-22 years old, and used a questionnaire to measure QoL. The search identified a total of 254 studies, and after exclusions, 11 relevant studies were included in the review. Most studies had a relatively small sample size, but overall included a total of 512 adolescents with PCOS. In most cases, adolescent girls with PCOS have reduced QoL when compared to healthy girls, and PCOS symptoms/excess weight impact on their QoL. Further research is required due to limited data on QoL in adolescents with PCOS of normal weight.

Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

INTRODUCTION: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. ß-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. MAIN RECOMMENDATIONS: This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.

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< 21 or > 45 days (> 1 to < 3 years post-menarche); cycles < 21 or > 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.

Curtailing PCOS.

Polycystic ovary syndrome (PCOS), characterized by hormonal imbalance and ovarian dysfunction, often starts during adolescence. Inconsistent diagnostic criteria, variable provider knowledge, and lack of consensus pose specific challenges for the care of women with PCOS. These factors encourage inaccurate diagnosis with both under and overdiagnosis. This unfavorable diagnostic experience exasperates affected women and limits timely opportunities for intervention to minimize associated comorbidities, especially during the transition from pediatric to adult care. Recognition of these issues in the care of adolescents and women with PCOS inspired the development of the International Evidence-Based PCOS Guidelines, which emphasize the prevention, screening, and treatment of PCOS across the reproductive lifespan. The Guidelines and accompanying meta-analyses focus on three major categories of associated comorbidities: (1) reproductive; (2) metabolic; and (3) psychological. With the exception of infertility, this article considers common manifestations and comorbidities associated with PCOS throughout the lifecycle. Healthy lifestyle interventions with prevention of excess weight gain comprise the primary intervention for all comorbidities. Hence, early identification of girls "at risk" for PCOS and those with PCOS is a priority. Extensive guidelines for provider and patient education aim to decrease the medical, psychosocial, and economic burdens attributable to PCOS and its associated comorbidities.

What is adolescent polycystic ovary syndrome?

The diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been derived from adult criteria, which makes diagnosis challenging as criteria include normal physiological events that occur during puberty such as acne, hirsutism, menstrual irregularities, high androgen levels and polycystic ovarian morphology on pelvic ultrasound. The only criteria that applies from the adult criteria is exclusion of other conditions that mimic PCOS. Clinical findings consistent with hyperandrogenaemia during adolescence include inflammatory acne, hirsutism, alopecia and/or menstrual irregularities, which are severe and present 2 years after menarche. The measurement of androgen levels during adolescence should take into account age, puberty, type of androgen measured, assay used and diurnal rhythm. Multiple measurements are useful to demonstrate hyperandrogenaemia. The combination, severity and persistence of the hyperandrogenic symptoms and hyperandrogenaemia in girls 2 years or more post-menarche support the diagnosis of adolescent PCOS. Adolescent girls with these findings should be followed up into adulthood.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.