Polycystic Ovary Syndrome In Adolescents Research Articles

8558 Prevalence of Polycystic Ovary Syndrome in Adolescent Girls by World Health Organization Region

Abstract Disclosure: S. Hatoum: None. M. Amiri: None. R.P. Buyalos: None. A. Sheidaei: None. R. Azziz: Consulting Fee; Self; Spruce Bioscience, May Health, Core Access Surgical Technologies, Acacia Bio, Fortress Biotech, Rani Therapeutics. Stock Owner; Self; Martin Imaging. Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. The use of several diagnostic criteria imposes a challenge for healthcare providers, especially in adolescents, whose PCOS symptoms may mimic normal pubertal changes. Objectives: This systematic review and meta-analysis aims to estimate the pooled prevalence of PCOS in adolescents using various diagnostic criteria in total and by WHO region. Methods: We systematically reviewed Pubmed and Embase through July 2023 to capture all studies performed in medically unbiased adolescent populations (age <18 years) reporting PCOS prevalence. Studies were categorized according to: a) PCOS criteria (NIH 1990 [PCOS phenotypes A&B], AE-PCOS 2006 [PCOS phenotypes A-C], Rotterdam 2003 [PCOS phenotypes A-D], and ‘other/self-reported’ criteria); b) subject assessment type (direct assessment, survey/indirect assessment, or mixed assessment); and c) study quality, assessed using the PCOS Epidemiology and Phenotype (PEP) quality assessment tool. We performed a meta-analysis using fixed-effects or random-effects models depending on the heterogeneity among the studies. We conducted subgroup analyses based on PCOS criteria, assessment type, study quality, and WHO region. Results: 6,644 studies were initially retrieved, of which 11 were eligible for inclusion including a total of 10,516 adolescents, yielding 15 study groups according to the diagnostic criteria. Considering all studies, PCOS prevalence was 4.98% according to the NIH 1990, 8.80% according to Rotterdam 2003, 4.74% according to the AE-PCOS 2006, and 1.69% according to other criteria/self-report, with an overall pooled PCOS prevalence of 4.57%. All studies using NIH 1990, Rotterdam 2003, and AE-PCOS 2006 were of high quality, and those using other criteria/self-report were of low quality, thus subgroup analysis based on quality resulted in the same prevalences as above. When including only high-quality studies that used direct or mixed assessment, PCOS prevalence was highest in the Western Pacific Region (WPR) at 20.69% and lowest in the Eastern Mediterranean Region at 3.43% under Rotterdam 2003, while it was highest in the South-East Asia Region at 6.20% and lowest in the WPR at 3.94% under NIH 1990. Only one high-quality study using direct or mixed assessment was available under AE-PCOS 2006. Conclusion: This meta-analysis revealed that PCOS prevalence varies according to the PCOS criteria, assessment type, and WHO region. This variability should be addressed, ideally through unifying the diagnostic criteria and using meticulous methods in PCOS epidemiologic studies. The effect of study quality alone on PCOS prevalence could not be detected because of insufficient data, further reinforcing the need for undertaking PCOS prevalence studies in all populations and regions. Presentation: 6/2/2024

7980 Physical Activity Attenuates the Association of Early Adolescent Adiposity with Later PCOS

Abstract Disclosure: R. Whooten: None. S. Rifas-Shiman: None. W. Perng: None. J. Chavarro: None. E. Oken: None. M. Hivert: None. Purpose: Adiposity is a risk factor for polycystic ovary syndrome (PCOS). Limited knowledge exists regarding modifiable behaviors, such as physical activity, during early-life may mitigate the association of adiposity with PCOS risk. We aimed to assess how moderate-vigorous physical activity (MVPA) may impact the association of adiposity in early adolescence with later report of adolescent PCOS. Methods: Within the Project Viva prospective cohort, we used multivariable logistic regression to assess the association of body mass index z-score (BMIz) at early adolescence (mean age 13.1 years) with mid-late adolescent PCOS (self-reported diagnosis or oligo-anovulation with clinical/biochemical hyperandrogenism at mean age 17.7 years). We stratified our analyses by actigraphy-assessed MVPA during early adolescence (≥30 versus <30 minutes/day). In multivariable models, we adjusted for maternal education and PCOS; and child race and ethnicity, dietary behaviors, actigraphy-assessed sleep duration, and self-reported screentime; and season of actigraphy assessment. Results: Among 341 female adolescents, n=47 (14%) met criteria for PCOS at mid-late adolescence. At early adolescence, mean (SD) BMIz was 0.32 (1.10) units and n=110 (32%) had ≥30 minutes/day MVPA. There was no difference in MVPA ≥30 minutes/day among those with versus without later PCOS (30% vs 33%, p=0.70). In unadjusted analyses, there was an association of early adolescent BMIz with mid-late adolescent PCOS (OR=1.93, 95%CI 1.39, 2.69 per unit increase in BMIz). In stratified analyses, the association of early adolescent adiposity with later PCOS was stronger in those with MVPA <30 minutes/day (OR=2.07, 95%CI 1.37, 3.11) than in those with MVPA ≥30 minutes/day (OR=1.72, 95%CI 0.97, 3.06). These findings persisted after adjusting for all covariates (overall: OR=1.72 95%CI 1.15, 2.56; MVPA <30 min/day: OR=2.01 95%CI 1.17, 3.45; MVPA ≥30 minutes/day: OR=1.36 95%CI 0.64, 2.91), however p-values for interaction terms were non-significant. Conclusion: Our findings suggest that maintaining ≥30 minutes MVPA daily during early adolescence may attenuate the association of adiposity with risk of PCOS by late adolescence. This has implications for the importance of promoting physical activity among at-risk individuals. Presentation: 6/2/2024

6420 Organokines and Liver Enzymes in Adolescent Girls with Polycystic Ovary Syndrome During Randomized Treatments

Abstract Disclosure: C. Garcia-Beltran: None. M. Peyrou: None. F.E. de Zegher: None. A. López-Bermejo: None. F. Villarroya: None. L. Ibanez: None. Introduction: Polycystic ovary syndrome (PCOS) is often related to metabolic associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function and systemic dysmetabolism and with abnormal circulating levels of signaling molecules, so-called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage which were assessed longitudinally in the aforementioned studies as safety markers. Materials and Methods: Liver enzymes [aspartate aminotransferase (AST), alanine amino transferase (ALT) and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) to those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 yr. As a post-hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI) and meteorin-like protein (METRNL), were assessed by ELISA after 6 months on OC (N=26) or spiomet (N= 28). Auxological, endocrine-metabolic, body composition (by DXA) and abdominal fat partitioning (by MRI) were also evaluated. Healthy age-matched adolescent girls (N=17) served as controls. Results: Circulating ALT and GGT levels raised during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 mo on treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls as compared to controls and spiomet-treated girls; (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels directly correlated with circulating METRNL levels only in OC-treated girls (R=0.449; P=0.036 and R=0.552; P=0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls associates with circulating METRNL levels suggesting an enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Trial registration numbers: ISRCTN29234515 (https://doi.org/10.1186/ISRCTN29234515) and ISRCTN11062950 (https://doi.org/10.1186/ISRCTN11062950) Presentation: 6/2/2024

6420 Organokines and Liver Enzymes in Adolescent Girls with Polycystic Ovary Syndrome During Randomized Treatments

Abstract Disclosure: C. Garcia-Beltran: None. M. Peyrou: None. F.E. de Zegher: None. A. López-Bermejo: None. F. Villarroya: None. L. Ibanez: None. Introduction: Polycystic ovary syndrome (PCOS) is often related to metabolic associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function and systemic dysmetabolism and with abnormal circulating levels of signaling molecules, so-called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage which were assessed longitudinally in the aforementioned studies as safety markers. Materials and Methods: Liver enzymes [aspartate aminotransferase (AST), alanine amino transferase (ALT) and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) to those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 yr. As a post-hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI) and meteorin-like protein (METRNL), were assessed by ELISA after 6 months on OC (N=26) or spiomet (N= 28). Auxological, endocrine-metabolic, body composition (by DXA) and abdominal fat partitioning (by MRI) were also evaluated. Healthy age-matched adolescent girls (N=17) served as controls. Results: Circulating ALT and GGT levels raised during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 mo on treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls as compared to controls and spiomet-treated girls; (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels directly correlated with circulating METRNL levels only in OC-treated girls (R=0.449; P=0.036 and R=0.552; P=0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls associates with circulating METRNL levels suggesting an enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Trial registration numbers: ISRCTN29234515 (https://doi.org/10.1186/ISRCTN29234515) and ISRCTN11062950 (https://doi.org/10.1186/ISRCTN11062950) Presentation: 6/2/2024

Prevalence and accurate diagnosis of polycystic ovary syndrome in adolescents across world regions: a systematic review and meta-analysis.

To examine the global prevalence of polycystic ovary syndrome (PCOS) among adolescents across world regions, comparing the 2003 Rotterdam consensus criteria with the current International Evidence-based PCOS Guideline criteria which omits polycystic ovarian morphology (PCOM). Systematic review and meta-analysis, Prospero CRD42022372029. OVID MEDLINE, All EBM, PsycInfo, EMBASE, and CINAHL were searched from 1990 to November 2023 for studies assessing the prevalence of PCOS in unselected adolescent populations. Overall, 15 708 articles were identified. After removal of duplicates, 11 868 titles and abstracts and 445 full texts were assessed. Of these, 24 articles reporting on 23 studies from five world regions were included. In meta-analysis of 20 studies (n = 14 010 adolescents), global prevalence was 9.8% (95% CI 7.2, 12.3) according to original Rotterdam criteria, and 6.3% (95% CI 3.9, 8.8) according to International Evidence-based Guideline criteria. Global PCOS prevalence based on self-report was 9.8% (95% CI 5.5, 14.1). Grouped by WHO region, prevalence ranged from 2.9% (95% CI 2.0, 3.9) in the Western Pacific region to 11.4% (95% CI 7.1, 15.7) in the South-East Asia region according to guideline criteria. This paramount global meta-analysis on adolescent PCOS diagnosis directly informed the 2023 International PCOS Guideline. Guideline criteria generated a global PCOS prevalence of 6.3%, compared with 9.8% on Rotterdam criteria (including PCOM). Excluding PCOM, which overlaps with normal pubertal transition, is expected to deter over-diagnosis. To avoid under-diagnosis, the Guideline recommends identifying those with either irregular cycles or hyperandrogenism as being "at risk"; this group should undergo longitudinal serial evaluations until adulthood.

Fundamentals to Diagnosing Polycystic Ovary Syndrome in Adolescents: A Critical Literature Review

Background: Because of this prevalence and frequent association with various comorbidites, the diagnosis of polycystic ovary syndrome (PCOS) must be performed as early as possible. Despite conflicting findings, many studies have been published on adolescents with a diagnosis of polycystic ovary syndrome. Methods: The Google Scholar and PubMed data bases were searched for publications in the English language reporting on PCOS diagnosis in adolescents. Results: A comprehensive analysis of data regarding the overlay of physiological ripening of menstrual cycle characteristics, androgen levels, and ovary aspects during puberty with the established criteria to diagnose PCOS in adults revealed that are liable diagnosis of PCOS in adolescence is possibleas soon as 2-3 years postmenarche. Persistant menstrual cycle intervals shorter than 21 days or longer than 45 days, total testosterone levels >1.9-2.0 nmol/l and ovary volume >10cm<sup>3 </sup>after 15-16 years of age can be used to diagnose PCOS. Conclusion: When combined, any persistent deviation of physiological parameters in adolescents as a criterion to diagnose PCOS in adults allows a certain diagnosis of PCOS in adolescents.

The Relationship Between Platelet Indices, Hormonal Status, and Insulin Resistance in Adolescents with Polycystic Ovary Syndrome: A Retrospective Case-Control Study

Aim: This study aimed to investigate the relationship between polycystic ovary syndrome in adolescents, a disease caused by inflammation and insulin resistance that is associated with metabolic disorders, and platelet indices, which provide information about platelet activity. Materials and methods: Patients with oligoovulation, hyperandrogenemia, or clinical signs of hyperandrogenism (hirsutism, acne, etc.) and polycystic appearance with ≥ 20 small follicles ≥ 2∼ 9 mm in diameter in both ovaries on ultrasound according to the newly updated Rotterdam criteria were included in the study with a diagnosis of polycystic ovary syndrome and formed PCOS group. Patients with similar age groups and body mass index (BMI) values who presented to the clinic for non-PCOS symptoms (vaginitis, dysmenorrhea, cystitis), whose complete blood count was checked during hormone testing, and who did not meet the Rotterdam criteria were selected as the control group. Platelet indices found in routine blood count parameters (platelet large cell ratio (P-LCR), platelet distribution width (PDW) and mean platelet volume (MPV)) were analyzed between the two groups. In addition, the relationship between these indices and hormone status and insulin resistance in PCOS patients was analyzed. Patients with diabetes mellitus, hypertension, malignant diseases, cardiovascular diseases, essential thrombocytopenia or other blood diseases and patients taking medication were excluded. Results: In the study of 123 patients, there was no statistically significant difference between the groups in terms of age and body mass index (p:>0.05). When hemogram parameters were compared between the groups, hemogram parameters such as P-LCR (p: 0.002), PDW (p: 0.011) and MPV (p: 0.007), which indicate platelet activity, were statistically significantly higher in the PCOS group. When the data of PCOS patients were analyzed, platelet indices were found to be higher in the group with high insulin resistance (p:

The possible short-term of Nigella sativa – L in the management of adolescent polycystic ovarian syndrome: results of a randomized controlled trial

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents.MethodsThe current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman–Gallwey score) levels were evaluated before and after the study.ResultsData from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001).ConclusionsShort-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS.IRCT registration numberIRCT20221017056209N1 Registration date: 2022-11-22.

P-658 Identification of novel biomarkers for the detection of polycystic ovary syndrome (PCOS) in adolescents and adult women

Abstract Study question Can novel biomarkers be identified to distinguish between PCOS-positive cases and healthy PCOS-negative controls in women as early as adolescence? Summary answer Meteorin-like protein (METRNL), fibroblast growth factor binding protein-1 (FGFBP1) and leukotriene A4 hydrolase (LTA4H) identified PCOS as early as adolescence, independent of PCOS phenotype. What is known already International evidence-based guidelines recommend use of the Rotterdam criteria for PCOS diagnosis. Despite this guidance, diagnosing PCOS can be extremely challenging due to the heterogeneity of clinical presentation, and further complicated in adolescence and young adulthood due to overlap between signs of physiologic changes during puberty and common symptoms of PCOS (e.g., menstrual irregularity, excess male hormones/androgens, multiple follicles in ovaries). Timely diagnosis of PCOS allowing for appropriate monitoring, follow up and early intervention may reduce the risk of associated comorbidities. An unmet need exists for biomarkers/alternative tools to support earlier diagnosis of PCOS in adolescents/adult women of reproductive age. Study design, size, duration This was a retrospective study (October 2020–June 2023) using banked samples from women with PCOS (confirmed per Rotterdam criteria) and healthy controls who had participated in previous studies sponsored by/in collaboration with Roche Diagnostics. Candidate biomarkers identified by exploratory proteomics analysis (Olink Proximity Extension Assay) were verified by ELISA and receiver operating characteristic-area under the curve (ROC-AUC) analysis for their ability to discriminate PCOS cases and controls in women aged 15-45 years. Participants/materials, setting, methods Top-performing biomarkers from Olink discovery (n = 51 PCOS phenotype A; n = 37 controls) were selected for further validation based on AUC &amp;gt;0.970, biological relevance for PCOS and commercial ELISA availability. Serum biomarker concentrations/biomarker ratios were determined and ROC-AUC analysis conducted in two validation cohorts (Cohort 1: n = 90 cases [phenotype A, n = 30; B, n = 20; C, n = 20; D, n = 20]; n = 47 controls; Cohort 2: n = 240 cases [15-19 years, n = 70; 20-24 years, n = 99; 25-40 years, n = 71]; n = 48 controls, median 26.0 years). Main results and the role of chance Serum METRNL concentrations were numerically lower, and FGFBP1 and LTA4H concentrations numerically higher, in PCOS cases compared with controls. All three biomarkers distinguished PCOS cases and controls, regardless of PCOS phenotype A-D (Cohort 1: AUCs 0.91-0.99 [METRNL], 0.84-0.88 [FGFBP1] and 0.76-0.90 [LTA4H]), and across different age groups in women of reproductive age (Cohort 2: 15-19, 20-24 and 25-40 years; AUCs 0.88, 0.91 and 0.96 [METRNL], respectively; 0.90, 0.88 and 0.91 [FGFBP1], respectively; 0.74, 0.70 and 0.78 [LTA4H], respectively). Compared with results for the individual biomarkers, combining FGFBP1 with METRNL, and LTA4H with METRNL, as biomarker ratios further improved the ability to distinguish PCOS cases and controls, independent of PCOS phenotype A-D (Cohort 1: AUCs 0.95-1.00 [FGFBP1:METRNL] and 0.97-0.99 [LTA4H:METRNL]) and across age groups (Cohort 2: 15-19, 20-24 and 25-40 years; AUCs 0.91, 0.96 and 0.98 [FGFBP1:METRNL], respectively, and 0.91, 0.91 and 0.97 [LTA4H:METRNL], respectively). Findings were not impacted by adjustment for baseline body mass index. METRNL, FGFBP1 and LTA4H are linked to biological mechanisms associated with clinical manifestations and underlying characteristics of PCOS, i.e., metabolic pathways, inflammation and ovarian function. While METRNL has been described previously in adult PCOS, FGFBP1 and LTA4H findings are novel in this context. Limitations, reasons for caution These findings in retrospective samples warrant validation in additional independent prospective cohorts, particularly in adolescents and young adult women. Wider implications of the findings Reliable diagnosis of PCOS in adolescents and young adult women represents an unmet medical need. METRNL, FGFBP1 and LTA4H have potential use as biomarkers to support the detection of PCOS in adolescents and adult women, potentially shortening time to diagnosis and allowing for earlier and targeted intervention. Trial registration number not applicable

Comparison of Diagnosis Experiences of Adolescent and Young Adult Polycystic Ovary Syndrome Patients

Study objectiveThe manner in which an individual experiences a polycystic ovary syndrome (PCOS) diagnosis may affect prognosis and vary with age. This study aimed to evaluate and compare the diagnosis experiences of adolescent and young adult PCOS patients. MethodsPCOS patients from the same institution were divided into two groups according to age and clinic (adolescents diagnosed in the adolescent medicine clinic and young adults diagnosed in the obstetrics and gynecology clinic). Patients completed a questionnaire designed to assess the information and support received during diagnosis, their satisfaction with this information, existing concerns regarding PCOS symptoms, and support requirements. ResultsThirty-six patients were included in each group. Among the participants, 52.8% of the adolescents and 63.9% of the young adults reported that they had consulted more than one specialist before receiving a diagnosis. We found that 83.3% of adolescents and 63.9% of young adults were satisfied with their overall PCOS diagnosis experience. The highest ratio of information given in both groups was related to medical treatment (88.9% in both groups), and the lowest ratios were associated with emotional support (13.9% vs.5.6%). Irregular menstruation was reported to be the most disturbing concern in both groups (94.4% vs.86.1%), and the biggest difference between the two groups was related to body dissatisfaction, which was observed more in adolescents (33.3% vs 5.6%). ConclusionWhile overall diagnosis experiences and satisfaction levels were similar across both groups, we identified distinct differences that may warrant attention to address age-specific needs and preferences.

Impact of the difference in diagnostic criteria for adolescent polycystic ovary syndrome excluding polycystic ovarian morphology.

Exclusion of polycystic ovarian morphology (PCOM) from the diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been proposed. We analyzed the profiles of adolescent women with suspected PCOS based on the Japan Society of Obstetrics and Gynecology (JSOG) diagnostic and Rotterdam criteria, excluding those with PCOM. Thirteen- to twenty-one-year-old women with suspected or confirmed diagnosis of PCOS according to the JSOG and Rotterdam criteria were included in this study. Patient characteristics such as hormone levels and body mass index (BMI) were compared between the groups. Correlations between BMI and testosterone, and BMI and time to diagnosis were also analyzed. Twenty-nine patients were diagnosed with adolescent PCOS according to the JSOG criteria, and 11 patients according to the Rotterdam criteria after excluding the patients fulfilling the PCOM criteria. Serum testosterone levels were significantly higher in adolescents diagnosed with PCOS using the Rotterdam criteria than in those diagnosed using the JSOG criteria (p < 0.001). The obese group had significantly higher testosterone levels and a longer time from menarche to PCOS diagnosis. A positive correlation was observed between BMI and testosterone levels (r = 0.318, p = 0.014). Although adolescents with PCOS diagnosed using the Rotterdam criteria exhibited higher testosterone levels, which is a typical characteristic of this condition, the JSOG criteria may be useful for the early diagnosis of adolescent PCOS, including suspected cases. The differences between the two criteria may reflect the natural history of PCOS and its different reproductive and metabolic phenotypes.

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments.

Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers. Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls. Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively). The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

Systematic exploration of network pharmacology, in silico modeling and pharmacokinetic profiling for vitamin E in polycystic ovarian syndrome.

Aim: This study seeks to explore the possibility of using vitamin E to alleviate the symptoms of polycystic ovarian syndrome (PCOS). Methods: Various computational methods were employed, including network pharmacology utilizing a compound-target-pathway approach, Swiss ADME, OSIRIS® property explorer, pkCSM, PASS online web resource and MOLINSPIRATION® software. In addition, in silico analysis of vitamin E was performed with ten receptors. Results & discussion: Our findings highlight the diverse potential of vitamin E in alleviating PCOS. The observed influence on hormones is in line with existing PCOS theories regarding cyst development, further enhancing the therapeutic promise of vitamin E. Conclusion: In conclusion, our computational analysis indicates that vitamin E shows potential as a therapeutic agent for alleviating PCOS in adolescents.

Letter to the Editor From de Zegher and Ibáñez: "Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome".

Letter to the Editor From de Zegher and Ibáñez: "Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome".

Response to Letter to the Editor from de Zegher and Ibáñez: "Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome".

Response to Letter to the Editor from de Zegher and Ibáñez: "Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome".

Comparative Management Methods for Adolescents With Polycystic Ovarian Syndrome: A Systemic Review.

Polycystic ovarian syndrome (PCOS) is a common endocrinological disorder affecting many adolescents and women of reproductive age worldwide. A diagnosis of PCOS in adolescence relies upon investigating each medical history independently and noting commonly associated symptoms, including obesity, insulin resistance, acne, menstrual abnormalities, and hirsutism. Many researchers are aiming to discover a methodology to help manage the symptoms associated with PCOS, especially in adolescents. This review will investigate management methods possible for adolescents with PCOS. Although the most preferred way to help reduce symptoms is through lifestyle modifications such as vigorous exercise and dietary regimens low in carbohydrates, pharmaceuticals are also offering promising results to adolescents with PCOS. Metformin, oral contraceptives, gonadotropin-releasing hormone (GnRH) antagonists, and other alternatives, including finasteride, eflornithine, fibroblast growth factors (FGFs), and vitamin D, are all shown to help improve insulin sensitivity and regulate menstrual cycles and reduce hirsutism. Epilatory and surgical measurements are also available; however, they are reserved for when all other methods fail and once adulthood or an appropriate age is reached. Although there are many pharmaceuticals available, it is necessary to evaluate each adolescent with PCOS uniquely and prescribe the appropriate pharmacotherapy regarding their symptoms.

Association of anti-Müllerian hormone and insulin resistance in adolescent girls with polycystic ovary syndrome.

Insulin resistance (IR) is confirmed as an important feature among polycystic ovary syndrome (PCOS) patients. Anti-Müllerian hormone (AMH), a vital marker of ovarian dysfunction, is proposed for inclusion in the diagnosis of PCOS in adolescents. We sought to investigate the relationship between the AMH level and IR in Chinese girls with PCOS. 92 girls with PCOS aged 14-18 years were enrolled and divided into 2 subgroups: PCOS with IR group (n = 25) and PCOS without IR group (n = 67). A homeostasis model assessment-insulin resistance (HOMA-IR) value ≥ 2.5 was defined as IR. Clinical data and biochemical indexes were compared between the 2 groups. Multivariate logistic regression analysis and multivariate linear regression analysis were performed to determine which clinical variables were independently associated with IR and AMH level, respectively. PCOS girls with IR had higher levels of AMH than those of PCOS girls without IR (p < 0.01). Moreover, body mass index, triglyceride, and AMH values were shown to be independent risk factors for HOMA-IR after multivariate analysis. Meanwhile, age, insulin, and follicle-stimulating hormone levels were significantly related to AMH levels in those girls. Our findings show that AMH is an independent determinant of IR in PCOS adolescents, and the fasting insulin level is closely associated with the AMH level, which indicates that the AMH pathway might play a role in the development of IR in PCOS adolescents. The interaction between AMH and IR in PCOS girls warrants further large-scale evaluation.

Management of Adolescent PCOD: A Real Challenge

Background: Polycystic Ovary Syndrome (PCOS) is a common hormonal disorder affecting 5-10% of women worldwide, characterized by irregular menstrual cycles and cysts on the ovaries. Its exact cause is unknown, but early identification and intervention can reduce the risk of complications like diabetes and heart disease. PCOS manifests in various ways, impacting reproductive, cosmetic, metabolic, and psychological aspects. Prevalence is higher in certain ethnic groups, and diagnosis can occur in adolescence but is often delayed. Despite its global impact, most studies focus on developed countries. Aim of the study: The study aims to explore the diagnosis and treatment procedures for managing adolescent PCOD in Bangladesh. Methods: This study, conducted at the Holly lab hospital &amp;Missionary Hospital Brahmanbaria, Bangladesh. The study spanned one year from January 2023 to December 2023. Diagnosis relied on clinical and biochemical evidence of hyperandrogenism and persistent menstrual irregularities. A one-on-one interview gathered comprehensive medical information. Inclusion criteria covered females aged 10 to 19, while exclusions involved specific medical conditions and ongoing treatments. Statistical analyses using SPSS included expressing variables and logistic regression to identify metabolic syndrome risk factors. The significance level was set at p ≤ 0.05 for statistical relevance. Result: The study involves 107 adolescent participants with Polycystic Ovary Syndrome (PCOD). Most were aged 10-15 (55.14%) with an average age of 16.8. BMI analysis showed high prevalence of overweight (29.70%) and obesity (39.40%). Abdominal obesity was normal in 76.60%, while 20.00% were pre-hypertensive, and 3.40% had hypertension. Glycemic status varied, with 76.00% normoglycemic, 21.10% prediabetic, and 2.90% diabetic. Dyslipidemia was present in 90.90%, and metabolic syndrome in 42.30%. Biochemical hyperandrogenism was observed in 33.70%. PCOD features included hirsutism (94.90%) and menstrual irregularities (oligomenorrhea 87.85%). Ovarian morphology showed diverse patterns. Hyperandrogenism, ovulatory dysfunction, ovarian morphology, and metabolic factors were primary contributors to PCOD diagnosis. Treatment approaches varied, including classical interventions (34.58%), lifestyle changes (14.95%), combined oral contraception (12.15%), and antiandrogens (7.48%). Therapeutic treatments included N-acetylcysteine, Inositol, Vitamin D supplementation, and Chromium supplementation. Conclusion: Managing adolescent Polycystic Ovary Syndrome (PCOS) is challenging due to the high prevalence of metabolic complications. Diagnostic complexity emphasizes careful evaluation to prevent premature labelling and psychological stress. Treatment involves lifestyle interventions, hormonal contraceptives, and anti-androgen medications. Standardized diagnostic criteria and a multidisciplinary approach are crucial. Early intervention and continuous monitoring are essential for mitigating long-term health risks. Further research on PCOS in diverse populations is recommended for tailored interventions and a nuanced understanding.

A Complete Overview of the Polycystic Ovarian Syndrome with Recent Advancement in Clinical Trial

Background: Polycystic ovarian syndrome (PCOS) has emerged as one of the most common endocrine and metabolic disorders seen in women of childbearing age throughout the whole world. The complex pathophysiology, different diagnostic criteria, and various manifestations attached to several environmental factors, including lifestyle influences, have made it one of the most difficult disorders to treat in recent times. In addition, inadequate knowledge among patients and a lack of dedicated approved medications have only enhanced the difficulties in treating such a heterogeneous disorder. Objective: The main objective of this review-type paper is to provide a detailed overview of PCOS along with the current concept of a clinical stance in this complex multigenic disorder. Method: The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents, the keywords “PCOS; hirsutism; psychological burden; obesity” and others of a similar nature were utilized. Conclusion: PCOS is a complicated hormonal, metabolic, and psychological condition with many different clinical manifestations. It is among the most prevalent causes of infertility. Before considering any medication choices, lifestyle modifications should be considered the primary therapeutic prescription for PCOS-related infertility. According to recent studies, PCOS does not affect the risk of ovarian or breast cancer, but it does raise the risk of endometrial cancer in women of all ages. These results suggest that PCOS may increase the risk of gynaecological cancer morbidity. The following stage is ovulation stimulation, which is best accomplished with letrozole and is followed by clomiphene citrate. Women who had not responded to the first-line oral ovulatory medicine were given gonadotropins as a backup. Early detection of girls with a high propensity to develop PCOS will be made possible by a comprehensive knowledge of the condition's etiology. Adolescent PCOS will be better managed overall, related comorbidities will be prevented, and quality of life will increase with customized therapeutic approaches.

Distinct Reproductive Phenotypes Segregate With Differences in Body Weight in Adolescent Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis. Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G. Reproductive phenotypes differed between the groups, with LN-G having higher total testosterone, androstenedione, and LH levels, while OB-G had lower sex hormone binding globulin (SHBG) and higher free testosterone. Metabolic profiles differed as expected, with OB-G having higher hemoglobin A1c, alanine aminotransferase, and serum triglycerides and more severe acanthosis nigricans. LN-G with PCOS had a distinct reproductive phenotype characterized by increased LH, total testosterone, and androstenedione levels, suggesting neuroendocrine-mediated ovarian androgen production. In contrast, phenotypes in OB-G suggest hyperandrogenemia is primarily driven by insulin resistance with low SHBG levels. These observations support the existence of distinct metabolic and reproductive subtypes in adolescent PCOS characterized by unique mechanisms for hyperandrogenemia.