Polycystic Ovary Syndrome Cases Research Articles

Phenotypes and clinical laboratory data for polycystic ovary syndrome cases: A nationwide survey in Japan.

Describe the current phenotypes and clinical laboratory data regarding polycystic ovary syndrome (PCOS) in Japan, taking into account ethnic differences and obesity status. Data for 986 PCOS cases and 965 control cases were collected using a nationwide survey in Japan. Obese/overweight (body mass index [BMI] ≥25 kg/m2) and non-obese/overweight (BMI <25 kg/m2) cases were compared. Japanese PCOS cases predominantly involved non-obese/overweight patients, accounting for 75% of all cases. Among non-obese/overweight PCOS cases, the incidence of both amenorrhea and clinical/biochemical hyperandrogenism was significantly lower than in obese/overweight PCOS cases, whereas the rate of elevated serum luteinizing hormone (LH) level was significantly higher. Even though the incidence of hirsutism in Japan is only 13.5%, the detection rate for hyperandrogenism increased by as much as 30.4% when hirsutism was added to the Japan Society of Obstetrics and Gynecology (JSOG) criteria for the diagnosis of hyperandrogenism in addition to elevated serum total testosterone level. When evaluated based on timing of blood sampling, the LH level and LH/follicle-stimulating hormone ratio determined at the initial consultation involving a chief complaint of irregular menstrual cycle (after confirming the absence of follicles measuring ≥1 cm in diameter) were significantly higher than on days 2-3 or 4-6 of the menstrual cycle. Ethnic differences, including obesity status, affected the phenotype and clinical laboratory data of Japanese PCOS patients, such as the incidence rates of clinical/biochemical hyperandrogenism and the rate of elevated basal LH level. Adding hirsutism to the JSOG 2024 criteria would enhance the accuracy of PCOS diagnosis and enhance consistency with the Rotterdam 2003 criteria. Measuring basal LH level is useful for assessing the endocrinologic characteristics of Japanese PCOS cases, as well as lean Asian PCOS cases, but the timing of blood sampling can affect the result.

A Comparative Analysis of Serum Irisin Levels and Body Composition Indices in Women With and Without Polycystic Ovary Syndrome (PCOS).

Introduction Polycystic ovarian syndrome (PCOS) is a prevalent endocrine-metabolic disorder impacting women of reproductive age, often manifesting during adolescence. This study aimed to determine serum irisin levels in subjects with PCOS compared to healthy controls and explore the correlation between irisin levels and body composition indices. Methods A cross-sectional study was conducted at a tertiary care hospital. Thirty-three women with PCOS and 32 healthy, age-matched controls were recruited. Relevant socio-demographic and clinical data were collected, and body composition was analyzed using bioelectrical impedance analysis (BIA). Serum irisin levels were measured using enzyme-linked immunosorbent assay (ELISA), and statistical analysis was performed using CoGuide software (Evidencian Research Associates, Bengaluru, India). Results PCOS subjects exhibited significantly higher levels of clinical features associated with hyperandrogenism, including elevated systolic (SBP) and diastolic blood pressure (DBP), body mass index, waist-hip ratio, total cholesterol, low-density lipoproteins (LDL), serum testosterone, body fat percentage, subcutaneous fat percentage, visceral fat percentage, and fat mass index, along with lower high-density lipoprotein levels and lean mass percentage, compared to controls. Serum irisin levels were significantly higher in PCOS cases (10.82 (8.5-14.31) ng/mL) than in controls (2.57 (2.19-4.65) ng/mL). There was a moderate positive correlation between serum irisin and SBP, DBP, hirsutism, total cholesterol, LDL, visceral fat, and serum testosterone levels. Weak correlations were observed between serum irisin and other body fat indices. Subjects with metabolic syndrome exhibited higher irisin levels and significantly elevated body composition indices, including body fat percentage, visceral fat percentage, fat mass index, and fat-free mass index, compared to those without metabolic syndrome. Conclusions PCOS subjects have elevated serum irisin levels, which correlate positively with clinical and biochemical hyperandrogenism, total cholesterol, LDL, and visceral fat. These findings suggest that irisin may play a role in the metabolic and hormonal dysregulation observed in PCOS.

Genomic association of SNPs rs4077582 of CYP11A1 and rs700519 of CYP19A1 genes with polycystic ovarian syndrome.

Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age. Several candidate genes have been shown to be associated with PCOS. Previous studies have shown that variations in CYP11A1 and CYP19A1 genes are associated with hormonal dysregulation associated with PCOS in different ethnic populations. This study aims to investigate the genomic association between SNPs rs4077582 of CYP11A1 and rs700519 of CYP19A1 and the development of PCOS in Pakistani population. A total of 280 subjects were recruited for the study, including 142 PCOS cases diagnosed based on Rotterdam criteria and 138 age-matched controls. The anthropometric, hormonal and biochemical parameters of all subjects were analyzed. Genomic DNA was extracted and genotyping of the selected SNPs was performed using Sanger sequencing. Further, we also examined the genotypic-phenotypic correlation analysis for various clinical and biochemical parameters for SNP rs4077582 of CYP11A1. We found significant differences in allele frequency (OR = 0.42, 95% CI = 0.30-0.60, χ2 = 16.3693, p = 0.000052) and genotypic frequency (χ2 = 26.4376, p = 0.00001) between PCOS women and controls for SNP rs4077582 of CYP11A1. Genotype-phenotype correlation analysis showed a significant difference in FAI (p = 0.005), testosterone (p = 0.001), androstenedione (p = 0.005) and urea (p = 0.049) levels between the three genotypes. No association between SNP rs700519 of CYP19A1 and PCOS was observed. Our results suggest the role of SNP rs4077582 of CYP11A1 gene in the clinical manifestation of PCOS in Pakistani women.

The Value IRS-1 rs1801278G &gt; A Polymorphism Testing in Evaluating Infertile Women with Polycystic Ovarian Syndrome: A Case-control Study

Background: Polycystic ovary syndrome (PCOS) is a leading cause of infertility. Insulin resistance is a key element in pathogenesis. The insulin receptor causes phosphorylation of the insulin receptor substrate (IRS); IRS-1 rs1801278G &gt; A polymorphism variant is the most common genetic variant associated with IR and PCOS. Objective: We aimed to examine the frequency of IRS-1 rs1801278G &gt; A polymorphism variant and test its value in evaluating infertile PCOS women. Methods: A case-control study recruited 140 age and body-mass-matched participants in the university hospital, subdivided according to Rotterdam criteria into PCOS cases (70/140) and healthy controls (70/140). We collected demographic data, ultrasonic [antral follicles and endometrial thickness], hormonal [FSH, LH, AMH, E2], and genetic data by polymerase chain reaction for analysis. Result: Wild GG SNP rs1801278 G was meaningfully higher among controls (58.57%, P&lt;0.0001). Mutant AA SNP rs1801278 was significantly higher in PCOS women (37.14%, P-value =0.0001, an odds ratio of 20.50, 95% CI (9.42-28.63) to develop PCOS. Heterogenous GA gene SNP rs1801278 showed a trend of higher frequency in PCOS patients with 44.29%; OR of 3.91, 95% CI (1.37–7.55); P = 0.422. Upon correlating infertility parameters to SNP rs1801278 G&gt;A polymorphism, statistical differences were found with AFC, LH/FSH ratio, and serum testosterone. As for the AMH, E2, and endometrial thickness, they failed to have a statistical value. Conclusion: The significant correlation of genetic polymorphism to infertility parameters among PCOS women opens a new therapeutic and prognostic avenue that helps gynecologists tailor manganate for a better and safer outcome.

EFFECTIVE AYURVEDIC APPROACH IN THE MANAGEMENT OF PCOS: A CASE REPORT

Nowadays, cases of Polycystic Ovarian Syndrome (PCOS) are rising very significantly, generally present in younger age groups due to faulty food habits, lifestyle, stress, etc. PCOS is a disease characterised by menstrual irregularities, elevated androgen levels and multiple cysts on one or both ovaries. A complex process is maintained by the intact uterine-adnexa and the hypothalamic-pituitary-ovarian axis in the female reproductive system. The normal functioning of the human body depends on the interdependence of all its systems, and any imbalance in one can lead to multisystem pathology. It is a common endocrinopathy, a multifactorial and polygenic condition resulting in anovulation or oligo-ovulation. In Ayurvedic classics, clinical features present in PCOS can be co-related with Pushpaghni Jataharini, Artavakshaya and Gulma roga. A 25-year-old female visited the OPD with complaints of irregular menstrual cycle, pimples and hair loss from the last six months. USG revealed Bilateral polycystic ovarian morphology. Oral administrations of shamana aushadhi have been done for three months. Regular menstrual cycles, along with improvements in symptoms, have been observed. Evidence for the complete cure of PCOS has produced an intriguing and positive outcome for researchers and professionals in this sector by following the principle of Gulma chikitsa. Shamana aushadhi, like Kanchanara Guggulu, Vriddhivadhika vati, Kumaryasava and Pathya churna, have shown excellent results in managing Polycystic Ovarian Syndrome.

Intra-ovarian Doppler artery indices values in cases with polycystic ovarian syndrome: a case control study

Background and objective: polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder during their reproductive age which results in hyperandrogenism and anovulation or oligo-ovulation. Significant changes occur in ovarian vascularization at the level of the intra ovarian arteries in PCOS patients. The objective is to assess Doppler hemodynamic changes in ovarian stromal arteries in follicular phase of the cycle in both ovaries in women with PCOS compared to normal ovulatory fertile women (control) using transvaginal Color Doppler technique, by calculating intra ovarian Doppler artery indices values: Resistive index (RI) and pulsatility index (PI) of both ovaries. Methods: Two hundred women were included in the study. One hundred patients were diagnosed as PCOS (cases) according to Rotterdam’s criteria and another one hundred were normal fertile women (controls). Transvaginal color Doppler technique is used in examining the recruited cases and controls, Doppler indices values of intraovarian stromal arteries were measured. Results: in the current study, the RI and PI of the ovarian stromal artery were lower in women with PCOS (cases) compared to controls. These hemodynamic changes are a predictor for the diagnosis of PCOS. Conclusion: Doppler ultrasonography was a successful tool in assessing the hemodynamic changes in PCOS women.

Genetic insights of blood lipid metabolites on polycystic ovary syndrome risk: a bidirectional two-sample Mendelian randomization study.

Pathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk. In this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites. This study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27-2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30-4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003-1.048, P=0.026). Genetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.

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

Prospective risk of Type 2 diabetes in 99892 Nordic women with polycystic ovary syndrome and 446055 controls: national cohort study from Denmark, Finland, and Sweden.

What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. The study cohort included women originating from Denmark (PCOS Denmark, N = 27016; controls, N = 133994), Finland (PCOS Finland, N = 20467; controls, N = 58051), and Sweden (PCOS Sweden, N = 52409; controls, N = 254010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99892; controls, N = 446055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. N/A.

Deep Learning Based Polycystic Ovary Syndrome (PCOS) Identification

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting reproductive-aged women, characterized by hormonal imbalance and ovarian cysts. Timely and accurate diagnosis of PCOS is crucial for effective management and prevention of associated complications. In this paper, we propose an automated diagnostic system for PCOS using deep learning and convolutional neural networks (CNNs). The dataset comprises ultrasound images of ovaries categorized into infected (PCOS) and not infected (non-PCOS) classes. Two CNN architectures, a deep CNN model and a CNN model with a last layer replaced by a support vector machine (SVM), are implemented and evaluated. Evaluation metrics include accuracy, precision, recall, and F1-score, demonstrating promising performance in accurately distinguishing between PCOS and non-PCOS cases. This automated diagnostic system offers a reliable and efficient approach for PCOS diagnosis, potentially reducing dependence on manual interpretation of ultrasound scans and improving healthcare outcomes for affected individuals. Key Words: Polycystic ovary syndrome (PCOS) , Deep learning, Convolutional neural networks (CNNs), Data augmentation, Ultrasound Scans

Unveiling Systemic Immune Inflammation Index Correlations in Women with Polycystic Ovary Syndrome: A Cross-sectional Study

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-age women that imposes metabolic and cardiovascular risks. Systemic immune inflammation index (SII), an inflammatory biomarker calculated from a complete blood count, was linked to many metabolic and cardiovascular illnesses. Objective: To evaluate the SII correlation with clinical, biochemical, and hormonal parameters characteristic of PCOS cases for screening and diagnostic values. Methods: For fifty PCOS patients who were eligible, we did a cross-sectional study and collected three types of information on each person: demographic information like age, menstrual cycle length, and body mass index (BMI); hormonal information like LH/FSH ratio, testosterone, and fasting insulin; and biochemical information like the homeostasis model assessment of insulin resistance (HOMA-IR), serum cholesterol, serum HDL, and serum LDL. The systemic inflammatory index (SII) was calculated from a complete blood count. Results: We found a strong positive correlation between SII and BMI, LH/FSH ratio, testosterone, fasting serum insulin, HOMA-IR, cholesterol, and LDL. However, the correlation between SII, HDL and menstrual cycle days was negative. Regarding the other parameters (HOMA-IR, testosterone, cholesterol, BMI, and LH/FSH ratio), the best subset regression model figures out how strongly SII is linked to each one. Conclusions: SII was strongly and significantly correlated to PCOS clinical, biochemical, and hormonal parameters, which makes it recommendable for screening. Its feasibility, affordability, and meaningful correlation inspired therapeutic and prognostic applications in practice.

Cut-off value for anti-Müllerian hormone in the diagnostic criteria for polycystic ovary syndrome in the Japanese population.

To establish cut-off values for anti-Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence-Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria. Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut-off values for AMH and AFC. Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut-off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20-29 and 30-39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut-off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH. The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria.

Spirulina versus metformin for controlling some insulin signaling pathway genes in induced polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50–70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using qRT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. Prospective observational study using data from the Japan Environment and Children's Study (JECS). Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Association between Dietary Inflammatory Index (DII) and the Risk of Polycystic Ovary Syndrome: A Case-Control Study

Background: Polycystic ovary syndrome (PCOS) is an inflammation-related condition and a common metabolic disorder in women at fertility ages. The Dietary Inflammatory Index (DII) is a validated nutritional tool for estimating the inflammatory potential of the diet. It is assumed that a high DII score (indicating a predominantly inflammatory diet) has an association with higher odds of PCOS. The current study aimed to investigate the association between DII and PCOS risk in women. Methods: This case-control study was conducted in 2019-2020 on 120 newly-diagnosed PCOS cases and 120 healthy controls aged 18-45 years in Khorramabad, Iran. DII was estimated based on a validated 168-item Food Frequency Questionnaire (FFQ). Results: The mean±SD of DII in PCOS patients was 0.40±2.09, while it was 0.45±1.92 in the control group (P&lt;0.001). There was a positive association between increasing DII score and the risk of PCOS (odds ratio= 2.41; 95%CI: 1.15-5.02, P for trend =0.006) in the crude model as the fourth quartile was compared with the lowest one. This association was still significant in several models after adjusting for age and energy intake (P for trend &lt;0.001), in the model adjusted for the physical activity level, education status, and family history of PCOS (P for trend=0.003), and also after additional adjustment for BMI (P for trend= 0.003). Conclusions: The present study revealed that consuming more pro-inflammatory diets with higher DII scores is related to an increased risk of PCOS.

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Comparative analysis of clinical symptoms and biochemical alterations in women with polycystic ovary syndrome: assessing the impact of type 1 diabetes versus non-diabetic controls

BackgroundWomen with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA.ResultsThe mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P < 0.001 and P = 0.010, respectively). PCOS was present in 11 (22.0%) of diabetic women compared to 3 (6.0%) in non-diabetics (P = 0.044). Diabetic women with PCOS received higher doses of insulin than non-PCOS women (72.7 ± 23.9 vs. 55.0 ± 19.8 UI.cc/ml/day, P = 0.023). PCOS women showed more frequent oligomenorrhea (100% vs. 15.4%, P < 0.001) and higher levels of total testosterone and insulin (0.64 ± 0.09 and 23.1 ± 13.0 vs. 0.53 ± 0.11 and 14.1 ± 11.8, P = 0.023 and P = 0.041, respectively). PCOS cases were significantly more frequent in diabetic women receiving intensive insulin therapy than their counterparts with non-intensive insulin therapy (40.9% vs. 7.1%, P = 0.012).ConclusionIntensive insulin treatment in type 1 diabetes potentiates the development of PCOS and its related clinical and biochemical features particularly oligomenorrhea, hyperinsulinemia, and hyperandrogenemia.

Pattern of body fat distribution in patients of PCOS using DEXA-based indices

BackgroundConsidering the close link between polycystic ovary syndrome (PCOS) and metabolic syndrome considerable research has been devoted to studying the pattern of fat distribution in PCOS.ObjectivesThe study aims to assess the usefulness of dual-energy X-ray absorptiometry (DEXA) based regional fat distribution indices as a predictor of the development of PCOS.MethodsThis case–control study recruited diagnosed cases of PCOS using Rotterdam Criteria (cases n = 86) and healthy age-matched controls (n = 90). DEXA was performed in both groups for assessment of total and regional body fat distribution after undergoing ultrasonography (USG) and baseline/biochemical evaluation.ResultsThe study revealed a significant difference between cases and controls in trunk fat percentage (40.2% ± 9.1% vs 26.5% ± 9.1%; p < 0.001), android fat percentage (42.4% ± 41%vs 27.8% ± 1.51%; p < 0.001), total fat percentage (43.8% ± 8% vs28.5% ± 1.6%; p < 0.001), fat mass/ht2 (fat mass index) (8.82 ± 3% vs 4.8 ± 1.7%; p < 0.001), android/gynoid ratio (1.05 ± 0.1 vs 0.7 ± 0.2; p < 0.001), and trunk/limb fat mass ratio (1.06 ± 0.3 vs 0.69 ± 0.3; p 0.001). Multivariate analysis revealed a significant relation of trunk fat mass with android % fat, gynoid fat mass, and android-gynoid ratio.ConclusionsThe study demonstrates that there is a central pattern of fat distribution in patients with PCOS while the overall fat might not be increased which is well analyzed by DEXA. Hence, we suggest its use in the initial diagnostic workup and follow-up of PCOS patients for their body fat distribution and content.