PCOS Cases Research Articles

Genetic associations of metabolic factors and therapeutic drug targets with polycystic ovary syndrome

IntroductionPolycystic ovary syndrome (PCOS) is frequently accompanied with metabolic dysfunctions, yet the causal relationships between metabolic factors and PCOS remain to be conclusively established and etiology-based therapies are lacking. ObjectivesTo comprehensively identify the metabolic causal factors and potential drug targets for PCOS. MethodsThis genetic association study was conducted using bidirectional two-sample Mendelian Randomization (MR), multivariable MR (MVMR) and drug-target MR. Considering metabolic sexual dimorphism, female-specific genome-wide association studies (GWASs) for metabolic factors were obtained. To ensure the robustness of the findings, an additional independent PCOS GWAS dataset was utilized for replication. ResultsThe PCOS cohort included 10,074 PCOS cases (mean age 28 to 45 years) and 103,164 controls (mean age 27 to 60 years) of European ancestry. All participants were female. Employing two-sample MR analysis, we found that genetically proxied body mass index (BMI) (OR = 3.40 [95 % CI, 2.65–4.36]), triglyceride (TG) (OR = 1.54 [95 % CI, 1.17–2.04]), low-density lipoprotein cholesterol (LDL-c) (OR = 1.37 [95 % CI, 1.07–1.76]), and type 2 diabetes (T2D) (OR = 1.24 [95 % CI, 1.09–1.41]) were significantly associated with an increased risk of PCOS, whereas genetically predicted high-density lipoprotein cholesterol (HDL-c) (OR = 0.61 [95 % CI, 0.47–0.80]) decreased the odds of PCOS. Stepwise MVMR established a hierarchy of interactions among these metabolic factors, identifying BMI and HDL-c as the most prominent causal factors. Notably, drug-target MR analysis identified incretin-based therapeutics, PCSK9 inhibitors, LPL gene therapy, sulfonylureas, and thiazolidinediones as potential therapeutics for PCOS. All these findings were validated in an independent dataset. ConclusionThis study offered insights into the roles of obesity, diabetes, and dyslipidemia in PCOS etiology and therapeutics, underscoring the necessity for managing metabolic health in women and paving the way for tailored therapeutic strategies for PCOS based on its metabolic underpinnings.

Polycystic ovary syndrome underdiagnosis patterns by individual-level and spatial social vulnerability measures.

To use electronic health records (EHR) data at Boston Medical Center (BMC) to identify individual-level and spatial predictors of missed diagnosis, among those who meet diagnostic criteria for PCOS. The BMC Clinical Data Warehouse was used to source patients who presented between October 1, 2003 and September 30, 2015 for any of the following: androgen blood tests, hirsutism, evaluation of menstrual regularity, pelvic ultrasound for any reason, or PCOS. Algorithm PCOS cases were identified as those with International Classification of disease (ICD) codes for irregular menstruation and either an ICD code for hirsutism, elevated testosterone lab, or polycystic ovarian morphology as identified using natural language processing on pelvic ultrasounds. Logistic regression models were used to estimate odds ratios (ORs) of missed PCOS diagnosis by age, race/ethnicity, education, primary language, body mass index (BMI), insurance type and social vulnerability index (SVI) score. In the 2003-2015 BMC-EHR PCOS at-risk cohort (n=23,786), there were 1,199 physician-diagnosed PCOS cases and 730 algorithm PCOS cases. In logistic regression models controlling for age, year, education, and SVI scores, Black/African American patients were more likely to have missed a PCOS diagnosis (OR = 1.69 [95% CI, 1.28, 2.24]) compared to non-Hispanic White patients, and relying on Medicaid or charity for insurance was associated with an increased odds of missed diagnosis when compared to private insurance (OR = 1.90 [95% CI, 1.47, 2.46], OR = 1.90 [95% CI, 1.41, 2.56], respectively). Higher SVI scores were associated with increased odds of missed diagnosis in univariate models. We observed individual-level and spatial disparities within the PCOS diagnosis. Further research should explore drivers of disparities for earlier intervention.

12500 Objective Evaluation Of Clustering Methods For Resolving The Heterogeneity Of PCOS

Abstract Disclosure: K. Brewer: None. R. Sisk: None. M. Dapas: None. C. Li: None. A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Self; Quest Diagnostics. Other; Self; Co-Editor Endocrine Today, Healio, Slack Inc. Clustering methods have been used to resolve heterogeneity within complex diseases to elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others have applied these methods to PCOS and identified discrete subtypes, including those that capture distinct reproductive or metabolic features. We objectively compared two widely used methods, hierarchical clustering (HC), which recursively merges subjects based on their similarity, and k-means (Km), which iteratively groups individuals to minimize their distance to cluster centroids. The number of clusters (k) was predefined in both approaches. We compared HC vs Km in 874 European ancestry PCOS cases diagnosed by NIH criteria using 8 traits (BMI, testosterone, SHBG, DHEAS, LH, FSH, fasting insulin, fasting glucose) and 9 traits with the addition of AMH. The ConsensusClusterPlus R package was used to evaluate cluster stability of both approaches with k=2, 3, or 4, using 8 or 9 traits. Genomewide association study (GWAS) meta-analysis was performed as reported with a discovery cohort (620 cases, 2951 controls) and a replication cohort (371 cases, 926 controls), except that genotypes were imputed to the newer TOPMED (r2) panel. Clustering using 8 traits and k=3 resulted in the best cluster stability for both HC and Km (pairwise consensus proportion: HC 0.98, Km 0.93) compared to k=2 with 8 traits (HC 0.88, Km 0.88) or 9 traits (HC 0.95, Km 0.92). No stability was observed for k=4 with 8 or 9 traits using either method (range: 0.35-0.66). Km showed slightly better cluster separation than HC (average silhouette width: Km 0.12 vs HC 0.09) with k=3 and 8 traits. The biologic relevance of the three PCOS subtypes, which we have designated as reproductive (cases with higher LH, FSH, SHBG), metabolic (higher BMI, insulin, glucose), and background, was assessed by GWAS, an orthogonal (i.e., uncorrelated) approach for subtype confirmation. The subtypes identified with HC had genomewide significant associations (metabolic subtype, c9orf3/FANCC, rs10761370, minor allele frequency [MAF] 0.47, p=1.21 x 10-8; background subtype, FSHB/ARL14EP, rs10835649, MAF 0.17, p=8.49 x 10-[1]0). There were no genomewide significant signals when the subtypes were identified with Km despite having a better cluster separation. In summary, only HC clusters appeared to capture biologically meaningful differences since two of the three subtypes thus identified were associated with genomewide significant loci. Neither the addition of AMH nor increasing the number of groups improved clustering metrics. Our results emphasize the importance of independent validation of clustering approaches using an orthogonal confirmation strategy such as GWAS. We conclude that HC clustering using 8 traits is superior to Km for resolving the genetic heterogeneity of PCOS. Presentation: 6/2/2024

12500 Objective Evaluation Of Clustering Methods For Resolving The Heterogeneity Of PCOS

Abstract Disclosure: K. Brewer: None. R. Sisk: None. M. Dapas: None. C. Li: None. A. Dunaif: Consulting Fee; Self; AcaciaBio, Inc, Neurocine Biosciences, Inc. Speaker; Self; Quest Diagnostics. Other; Self; Co-Editor Endocrine Today, Healio, Slack Inc. Clustering methods have been used to resolve heterogeneity within complex diseases to elucidate underlying biologic mechanisms. We (Dapas et al. PLoS Med, 2020) and others have applied these methods to PCOS and identified discrete subtypes, including those that capture distinct reproductive or metabolic features. We objectively compared two widely used methods, hierarchical clustering (HC), which recursively merges subjects based on their similarity, and k-means (Km), which iteratively groups individuals to minimize their distance to cluster centroids. The number of clusters (k) was predefined in both approaches. We compared HC vs Km in 874 European ancestry PCOS cases diagnosed by NIH criteria using 8 traits (BMI, testosterone, SHBG, DHEAS, LH, FSH, fasting insulin, fasting glucose) and 9 traits with the addition of AMH. The ConsensusClusterPlus R package was used to evaluate cluster stability of both approaches with k=2, 3, or 4, using 8 or 9 traits. Genomewide association study (GWAS) meta-analysis was performed as reported with a discovery cohort (620 cases, 2951 controls) and a replication cohort (371 cases, 926 controls), except that genotypes were imputed to the newer TOPMED (r2) panel. Clustering using 8 traits and k=3 resulted in the best cluster stability for both HC and Km (pairwise consensus proportion: HC 0.98, Km 0.93) compared to k=2 with 8 traits (HC 0.88, Km 0.88) or 9 traits (HC 0.95, Km 0.92). No stability was observed for k=4 with 8 or 9 traits using either method (range: 0.35-0.66). Km showed slightly better cluster separation than HC (average silhouette width: Km 0.12 vs HC 0.09) with k=3 and 8 traits. The biologic relevance of the three PCOS subtypes, which we have designated as reproductive (cases with higher LH, FSH, SHBG), metabolic (higher BMI, insulin, glucose), and background, was assessed by GWAS, an orthogonal (i.e., uncorrelated) approach for subtype confirmation. The subtypes identified with HC had genomewide significant associations (metabolic subtype, c9orf3/FANCC, rs10761370, minor allele frequency [MAF] 0.47, p=1.21 x 10-8; background subtype, FSHB/ARL14EP, rs10835649, MAF 0.17, p=8.49 x 10-[1]0). There were no genomewide significant signals when the subtypes were identified with Km despite having a better cluster separation. In summary, only HC clusters appeared to capture biologically meaningful differences since two of the three subtypes thus identified were associated with genomewide significant loci. Neither the addition of AMH nor increasing the number of groups improved clustering metrics. Our results emphasize the importance of independent validation of clustering approaches using an orthogonal confirmation strategy such as GWAS. We conclude that HC clustering using 8 traits is superior to Km for resolving the genetic heterogeneity of PCOS. Presentation: 6/2/2024

Unlocking the Triad of Health: Investigating High Blood Pressure, Obesity and their Impact on PCOS in Women

Polycystic Ovarian Syndrome or PCOS, is a common endocrine illness that affects 3.7% to 22.5% of fertile Indian women. It is characterised by abnormalities related to reproduction, metabolism, and hormones. This six-month prospective cohort study at Chalapathi Institute of Pharmaceutical Sciences examines the relationship between PCOS, obesity and high blood pressure. With 118 cases of PCOS detected among the 1246 participants who completed the comprehensive questionnaire, the study finds a substantial correlation between PCOS, obesity (p = 0.00061) and hypertension (p = 0.00061). Findings show that PCOS is more common in college students, underscoring the importance of lifestyle choices like nutrition, exercise and stress reduction. Additionally, the study finds that academics are more likely than IT workers or stay-at-home moms to have PCOS, which is associated with greater rates of obesity and hypertension. The results highlight the need for focused interventions, such as lifestyle changes and educational initiatives to reduce PCOS risk factors and enhance health outcomes. This study expands our understanding of PCOS and highlights the value of early detection and individualised treatment plans.

PREVALENCE OF POLYCYSTIC OVARIAN SYNDROME AMONG YOUNG WOMEN WHO ATTENDED TERTIARY CARE HOSPITAL, VISAKHAPATNAM

Objective: The present study aimed to determine the prevalence of PCOS among young adults attended to medical OP in a Tertiary care teaching hospital. Materials: It is a retrospective study conducted in a Tertiary care teaching hospital, Visakhapatnam using existing records in the Department of Obstetrics and Gynaecology. The study was conducted from July 2021 to July 2023. The study population includes young adults of age in between 18-30 y. PCOS was defined by Rotterdam's criteria having presence of any two of the three features. Hormonal assays were conducted using immunoradiometric assay for TSH, LH, FSH. Results: Majority of the PCOS cases 39% were reported in the age group of 26-30 Y. Among the 100 cases reported, the majority of them are reported with menstrual irregularity 62%. However, it was identified from the results that the mean values of cholesterol and triglycerides levels are quite higher suggested hyperlipidemia. The hormonal levels of TSH, LH and FSH were normal. Conclusion: Although the overall frequency of PCOS is low and evaluating PCOS in young adults can be difficult, the condition is becoming more common at this age. Changes in lifestyle are essential at this age to avoid long-term metabolic and reproductive issues.

Structural changes in amide I and amide II regions of PCOS women analyzed by ATR-FTIR spectroscopy

The etiology of PCOS is complex and frequently mis or undiagnosed, which may enhance morbidity and reduce the quality of life. Attenuated total reflection- Fourier transform infrared (ATR-FTIR) spectroscopy examines the structural fingerprints of the biochemical compounds and can provide distinct FTIR spectra of the PCOS cases and controls. The present study recruited 61 PCOS cases and 38 control women. The student's t-test was used to compare BMI, WHR, and lipid profile. The FTIR spectral region was compared among both groups using the Mann-Whitney U test and multivariate analysis involved principal component analysis (PCA) and hierarchical cluster analysis (HCA). FTIR spectra of different phenotypes of PCOS were also analyzed using multivariate analysis. In univariate analysis, PCOS women had significantly higher WHR (p = 0.007), BMI (p = 0.04), triglycerides (p = 0.04), and VLDL (p = 0.02) than the controls. The spectral regions of amide I (1700-1600 cm-1) and amide II (1580-1480 cm-1), were significantly greater in the PCOS group than in the controls (p < 0.01 and p < 0.001, respectively). The PCA and HCA revealed a distinct molecular fingerprint for phenotype A (PCOM + OA + HA) and phenotype B (HA + OA).Our study postulated that the spectral regions of amide I and amide II can distinguish between PCOS cases and control women and it may be used for the diagnosis of cases.

An Open Randomised Clinical Study to Evaluate the Combined Effect of Krishna Tila Kashayam and Shatapuspa Choornam in PCOS

PCOS has ovarian dysfunction along with hyperandrogenism and polycystic ovarian morphology. PCOS is a condition where involvement of Kapha dosha is present along with Vata dosha along with Rasa Dhatu, Medo dhatu and Arthava- the Upadhatu of Rasa is affected. Because of having the properties of Ushna virya, Kashaya Tiktha rasa, Arthava janana properties, Krishna Tila Kashayam and Shatapuspa choornam has been mentioned for the treatment of Arthava kshaya (anovulation and oligomenorrhea) in PCOS. The treatment is fully focused on Vata Kapha hara chikitsa and Arthava vardhaka. The drugs selected for the present study can be easily prepared and administered, cost effective. In this study, Tila kashayam along with Anupanam Gudam and Shatapuspa choornam along with Anupanam Madhu has been given and the results have been noted. In the present study, a total of 40 patients suffering from PCOS were selected from OPD and IPD of SJSACH. The thesis is widely focused on increasing the quantity of flow in amenorrhoea or oligomenorrhea cases, to check the size of the ovarian follicle before and after treatment and to check if there is any reduction in hair growth in hirsutism patients. There was a notable change seen in mild to moderate PCOS cases regarding the interval between 2 cycles, duration of flow between 2 cycles and quantity of flow between 2 cycles. There was a notable change seen in reduction of ovarian cyst volume before and after treatment. Hirsutism, BMI and waist circumference - there was no significant changes noted during these 3-month period.

TO ESTIMATE THE URIC ACID LEVELS IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS)

Background- Pcos is most common endocrine disorder now a day in females, it appears due to abnormalities in metabolism of androgen and estrogen. It is not only an endocrine disorder but also a metabolic, hormonal and psychological disorder. It causes infertility, distress, hirsutism, irregular menstrual, or biochemical findings. This study aims to evaluate the biochemical parameter, Uric Acid in PCOS women and to assess its effect in these patients and to compare the assessed parameter with that of normal controls. Methods - After applying inclusion and exclusion criteria, blood samples are collected from 50 menopausal women diagnosed to have PCOS by ultrasound and 50 healthy controls (Pre-Menopausal Women) aged 18-40 years. Serum Uric Acid was done in both PCOS patients and controls. The correlation between the biochemical parameters are studied in the PCOS group. Results- There was a significant increase in serum uric acid levels in PCOS patients as compared to controls. So, uric acid in PCOS cases as an indicators of early metabolic changes that can be used to diagnose PCOS women at risk of cardio metabolic syndrome. And also it showed that, increased uric acid levels in PCOS patients as compared to controls which were statistically significant. Conclusion- The findings of this study confirms the Uric acid in PCOS and may help to identify women with PCOS at risk of cardio metabolic syndrome, there by confirming the association between PCOS and cardiovascular risk factors.

Investigating the interplay between AMH gene polymorphism rs10407022 and clinical indicators in polycystic ovary syndrome

PurposePCOS is a multifaceted endocrine disorder with a complex etiology that includes genetic and environmental influences. The Anti-Mullerian Hormone is essential in menstrual disorders and fertility, as it is involved in growth differentiation and folliculogenesis. The AMH gene polymorphism, specifically p.Ile49Ser, has been proposed to play a role in the pathogenesis of PCOS, but its significance in Indian populations has yet to be determined. MethodsA case-control study was carried out on 129 women from Gujarat, India, aged 13 to 40 years (59 with PCOS and 70 controls). Clinical, biochemical, and hormonal parameters were examined, and tetra-ARMS PCR was used for genotyping the AMH gene polymorphism (p.Ile49Ser). The relationships between polymorphism, hormonal imbalances, and PCOS were studied using different statistical methods. ResultsThe mean BMI in the PCOS group was significantly higher (27.32 ± 5.71) in comparison to the control group (23.81 ± 5.47, p = 0.001), with 67.80% of PCOS cases being obese. Notably, serum LH and T levels were significantly higher in PCOS women, whereas DHEAS levels were significantly lower (p < 0.05). However, the distribution of AMH gene rs10407022 genotypes and alleles did not differ significantly between groups, and no associations with PCOS risk were found. ConclusionObesity and hormonal imbalances have a significant impact on PCOS in Gujarati women, according to this study. Even though the AMH gene polymorphism (p.Ile49Ser) did not show a significant association with PCOS, the findings encourage further genetic research in diverse Indian populations to uncover the complex genetic background of PCOS.

Treatment of Polycystic Ovarian Syndrome through Individualised Homoeopathic Medicine: Two Case Reports

AbstractPolycystic ovarian syndrome (PCOS) is one of the most common metabolic and reproductive disorders among women of reproductive age. Women suffering from PCOS present with menstrual dysfunction and androgen excess. Two patients aged 16 and 19 years suffering from PCOS were treated successfully with individualised homoeopathic medicine. These two cases of PCOS were treated with marked improvement within 1.5 years by individualised homoeopathic medicine with change in potency and repetition as per requirement. Modified Naranjo Criteria for Homeopathy (MONARCH) was used as a tool for attributing a causal relationship between the homoeopathic intervention and outcome. Visual analogue scale was used as a tool for assessing pain during menses (dysmenorrhoea). The improvement is evident from the regularity of the menstrual cycle, along with the resolution of cysts in ovaries as evidenced by ultrasonography reports which indicate a positive response of homoeopathy in relieving the symptoms as well as pathology associated with PCOS.

Surah Al Fatiha Induced Betterment of Menstrual Cycle and Hormonal Levels of PCOS: Evidence from Clinical Trials

Introduction Polycystic ovarian syndrome is an endocrinal disorder comprising multiple signs and symptoms that are associated with hormonal imbalance. The intervention was administered to subjects who were reluctant to go for pharmacological intervention. Methodology The designed study was intended to evaluate the effect of Surah Al Fatiha in combating PCOS pathology. Inclusion of females was from teenage to 45 years of age. Rotterdam criteria were used to diagnose 7 PCOS cases, while 7 healthy controls were recruited from the Mamji Hospital in Karachi's gynecology department. Surah Al Fatiha exposure was given to all the subjects. Exposure commenced on second day of subject’s menstrual cycle (three times daily) till the subsequent menstrual cycle started. Surah Al Fatiha, a pre-recorded version by ‘Qari Mishary Rashid Alafasy’ was used in this study. Biochemical parameters were monitored and evaluated before and after the Surah Al Fatiha therapy. Results revealed significantly decreased levels of hormones in PCOS afflicted females after Surah Al Fatiha exposure. Insulin and TSH were restored to their normal levels while rest of the hormones though decreased but were in normal range prior to the exposure of intervention. Conclusion Surah Al Fatiha exposure induces serenity and reduces stress, thus inducing normalization of TSH, decreased IR and in turn regularizing the menstrual cycle.

Comparison of physical activity levels and dietary habits between women with polycystic ovarian syndrome and healthy controls of reproductive age: a case-control study

BackgroundPolycystic ovarian syndrome (PCOS) is a reproductive hormonal anomaly prevalent among women of reproductive age, with an alarmingly high prevalence of 52% among Pakistani women. This study aims to compare the daily physical activity and dietary habits of women with PCOS with age-matched healthy controls living in Lahore, Pakistan.MethodsA case–control study design was used to collect data from a private hospital situated in Lahore, Pakistan. Data was collected from 115 participants of reproductive age (18–45 years) using a researcher-administered questionnaire. Demographic variables, reproductive characteristics, anthropometric measurements, and seven days of physical activity levels using the international physical activity questionnaire (IPAQ-Short version) and seven days of dietary intake using the food frequency questionnaire (7 days-FFQ) were used to measure the dietary habits of the participants. Mosby’s Nutritac v4.0 software was used to estimate the macronutrients, vitamins, and minerals present in dietary intake. The glycaemic index and glycaemic load were calculated to compare the quality and quantity of carbohydrate consumption between the two groups.ResultsThe 49 PCOS cases, newly identified using the Rotterdam criteria, mean age 24.63 years (SD ± 4.76), and 66 healthy controls, mean age 23.24 years (SD ± 5.45), were compared. A significant difference (p ≤ 0.05) was found for reproductive characteristics, daily physical activity, and polyunsaturated fat and vitamin intake between the two groups. A binary logistic regression analysis showed that food with a low glycaemic index (GI ≤ 40) reduced the odds of PCOS occurrence by OR = 1.94. Similarly, food nutrients with a low glycaemic load (GL ≤ 10) can reduce PCOS occurrence by OR = 1.60.ConclusionThe daily physical activity levels and dietary habits of women of reproductive age can influence their reproductive characteristics and polycystic ovarian morphology. A diet with a low glycaemic load and index can produce beneficial reproductive health effects among women of reproductive age.

An Update on the Genetics of Polycystic Ovary Syndrome

PCOS is a common endocrinopathy among women of reproductive age, with a worldwide prevalence of 8 to 13%, depending on the criteria used for diagnosis. It is characterized by a constellation of features, including oligo/anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS is one of the common causes of female infertility. It is also associated with metabolic derangements, including obesity, insulin resistance, and compensatory hyperinsulinemia, which increase the likelihood of developing type 2 diabetes mellitus. Despite extensive research, the etiology of PCOS remains largely unknown. It seems likely that the hypothalamic-pituitary-ovarian axis dysfunction, partial folliculogenesis arrest, insulin resistance, and ovarian and adrenal androgen secretion may play a role in the pathogenesis of PCOS. Familial clustering of the cases of PCOS points to a genetic component linked with it. The initial genetic studies suggest an autosomal dominant pattern of inheritance of the disorder in some families; however, most studies support multifactorial origin. Since PCOS is a complex trait, the typical form of inheritance of PCOS follows a non-Mendelian pattern and involves complex genetic mechanisms. Studies involving linkage and association have suggested a connection between genetic variations and the risk of developing PCOS in certain families or populations. Through genome-wide association studies and next-generation sequencing techniques, several candidate genes have been identified that play a role in the etiopathogenesis of the disorder. Pathogenic variants of various genes such as INSR, IRS1, GHRL, LDLR, MC4R, ADIPOQ, UCP1, UCP2, UCP3, FTO, PCSK9, FBN3, NEIL2, FDFT1, PCSK9, CYP11, CYP17, CYP21, HSD17, STAR, POR, AKR1C3, AMH, AMHR2, INHBA, AR, SHBG, LHR, FSHR, FSH β, SRD5A, GATA4, THADA, YAP1, ERBB2, DENND1A, FEM1B, FDFT1, NEIL2, TCF7L2, etc. in some PCOS cases are linked as underlying etiologic associations. This review aims to provide insight into the current genetic knowledge about PCOS. Discovering the genetic factors and pathways involved in the disorder will help us better comprehend the underlying mechanisms of the disorder.

Evaluation of CRP/Albumin Ratio in Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome is a common endocrine disorder among women of reproductive age. It is characterized by menstrual abnormalities, hyperandrogenism and polycystic ovaries and can lead to many complications. Studies have postulated the role of inflammation in the pathophysiology of PCOS. As acute phase reactants often serve as markers of inflammation, this study aimed to evaluate the role of inflammatory markers in women with PCOS and healthy controls. A total of 60 participants were enrolled; 30 cases of PCOS and 30 age matched healthy controls. Peripheral venous blood was collected for assessment of CRP, serum albumin, serum total testosterone, serum fasting insulin and fasting blood glucose, following which statistical analysis was done. The CRP/albumin ratio was found to be significantly higher in women with PCOS as compared to healthy controls along with serum total testosterone and HOMA-IR. Correlation between CRP/albumin ratio and the levels of serum total testosterone and insulin resistance was found to be non-significant. An elevated CRP/albumin ratio in cases of PCOS compared to healthy controls supports the hypothesis of inflammation playing a key role in the pathophysiology of PCOS. CRP/albumin ratio can serve as a cheaper biochemical marker of the disease subject to further validation studies to establish its use in Indian population.

Increased Prevalence of Adverse Health Outcomes Across the Lifespan in Those Affected by Polycystic Ovary Syndrome: A Canadian Population Cohort

BackgroundPolycystic ovary syndrome (PCOS) is the most common metabolic-endocrine disorder impacting the health and quality of life of women over the lifespan. Evidence-based data on the scope of adverse health outcomes in those affected by PCOS is critical to improve healthcare and quality of life in this population. The aim of this study was to determine the prevalence of adverse health outcomes in those with PCOS compared to age-matched controls. MethodsWe conducted a retrospective observational case-control study in those diagnosed with PCOS and age-matched controls using the Alberta Health Services Health Analytics database and the International Classification of Diseases, for the period from 2002-2018 in Alberta, Canada. ResultsThe cohort consisted of n = 16,531 exposed PCOS cases and n = 49,335 age-matched un-exposed controls. The prevalences of hypertension, renal disease, gastrointestinal disease, eating disorders, mental illness, depression-anxiety, rheumatoid arthritis, respiratory infections, and all malignancies were 20%-40% (P < 0.0001) higher in those with PCOS, compared to controls. The prevalence of obesity, dyslipidemia, nonalcoholic fatty liver disease, and type 2 diabetes was 2-3 fold higher in those with PCOS (P < 0.001). Cardiovascular, cerebrovascular, and peripheral vascular disease were 30%-50% higher, and they occurred 3-4 years earlier in those with PCOS (P < 0.0001); a 2-fold higher prevalence of dementia occurred in those with PCOS, compared to controls. ConclusionThese findings provide evidence that PCOS is associated with a higher prevalence of morbidities over the lifespan, and the potential scope of the healthcare burden in women affected by PCOS.

Effect of pilates on regulating menstrual cycle in females with polycystic ovarian syndrome

BackgroundPolycystic Ovarian Syndrome (PCOS) is the most common genetic disorder of the endocrine gland among females during the age of reproduction with an estimated prevalence ranging from 2.2 % to 26 %. It is a typical reason for ovulatory infertility, menstrual dysfunction, and hirsutism. It is a condition in which ovarian cysts develop with a diameter of between two and nine millimeters on one or each ovaries and therefore there is an increase in the volume of one is larger than ten millimeters. ObjectiveTo analyze the effect of pilates on pain and regulation of the menstrual cycle in females with PCOS. Research methodologyA single centered, quasi-experimental study, performed in Lovely Professional University, India on a total of 26 participants suffering from PCOS, based on inclusion and exclusion criteria. After a detailed assessment, the Pilates exercise protocol was given for 3 months i.e. 3 times per week. The readings for pain and regulation were taken at baseline, at the end of 1st, 2nd, and 3rd month using visual analog scale (VAS)and verbal multidimensional score sysem (VMSS). ResultsThe result findings indicates suggested that there is significant change in the pain (Wilk’s Lambda =.117, F(3,23) = 58.109, P < 0.05), variable during the menstruation in PCOS over the time of three months. The menstrual cycles were regularised and the cycle was shifted towards the normal parameters. The VMSS also shows changes that signify that Pilates is effective in PCOS complications. ConclusionThis study concluded that Pilates is effective in reducing the pain in PCOS cases which improves the working ability of the females and also regulates the menstrual cycles which were irregular at the beginning of the treatment.

A Machine Learning based Improvised Follicle Polycystic Ovarian Detection Through Ultrasound Images Through IOT

Polycystic ovarian syndrome which is commonly called as PCOS is a endocrine malfunction affecting women of reproductive age. Its diagnosis involves in detection of multiple small follicles mainly in the ovaries through ultrasound imaging. However, manual detection is time-consuming, subjective, and prone to errors. Hence, this study proposes an improvised follicle PCOS detection method using machine learning(Random Forest and Logistic Regression) from a sequence of given ultrasound images. The proposed method involves pre-processing the ultrasound images through IoT, followed by segmenting and extracting follicle features. Subsequently, a machine learning model is trained to classify the extracted features as normal or PCOS cases. The proposed method's performance is evaluated on a dataset of 400 ultrasound images from 50 patients, including 25 PCOS cases and 25 healthy controls. The experimental results demonstrate that the proposed method achieves a high classification accuracy of 93.75% and an AUC of 0.96. In addition, the proposed methodology outperforms in comparison with the state-of-the-art PCOS detection methods in terms of accuracy, sensitivity, specificity, and AUC. The proposed method also provides a quantitative measure of the severity of PCOS based on the number and size of the follicles detected.

Deciphering the DNA methylome in women with PCOS diagnosed using the new international evidence-based guidelines.

Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based guidelines? A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls. PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based guidelines. This cross-sectional case-control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls. A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites. We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952). The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required. This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based guideline, and it provided new molecular insight into the application of the new guidelines. This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest. N/A.

Examining the Genetic Role of rs8192675 Variant in Saudi Women Diagnosed with Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a complex disorder defined by the Rotterdam criteria. Insulin resistance is a common factor for the development of type 2 diabetes mellitus among women with PCOS. The SLC2A2 gene has been identified as a T2DM gene by genome-wide association studies in the rs8192675 SNP. This study aimed to investigate the rs8192675 SNP in women diagnosed with PCOS on a molecular level and further for T2DM development in the Saudi women. In this case-control study, 100 PCOS women and 100 healthy controls were selected. Among 100 PCOS women, 28 women showed T2DM development. Genotyping for rs8192675 SNP was performed by PCR-RFLP analysis. Additionally, Sanger sequencing was performed to validate the RFLP analysis. The obtained data were used for a statistical analysis for the genotype and allele frequencies, logistic regression, and ANOVA analysis. The clinical data confirmed the positive association between FBG, FI, FSH, TT, TC, HDLc, LDLc, and family histories (p < 0.05). HWE analysis was associated in both the PCOS cases and the control individuals. Genotype and allele frequencies were associated in PCOS women and strongly associated with women with PCOS who developed T2DM (p < 0.05). No association was found in the logistic regression model or ANOVA analysis studied in women with PCOS (p > 0.05). A strong association was observed between the rs8192675 SNP and women with PCOS who developed T2DM using ANOVA analysis (p < 0.05). This study confirms that the rs8192675 SNP is associated with women with PCOS and strongly associated with women with PCOS with developed T2DM in Saudi Arabia.