scholarly journals Polycystic Ovary Syndrome Susceptibility Loci Inform Disease Etiological Heterogeneity

2021 ◽  
Vol 10 (12) ◽  
pp. 2688
Author(s):  
Yanfei Zhang ◽  
Vani C. Movva ◽  
Marc S. Williams ◽  
Ming Ta Michael Lee
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Strong Association ◽  
Sex Hormone Binding Globulin ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Insulin Resistant ◽  
Disease Outcomes ◽  
Unclear Etiology

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We hypothesize that the heterogeneity of PCOS manifestations reflects different mechanistic pathways and can be identified using a genetic approach. We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS-related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effects between the traits and PCOS. Three categories of variants were identified: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in the insulin-resistant cluster with fasting insulin, glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization suggested a causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes.

scholarly journals Polycystic ovary syndrome susceptibility loci inform disease etiological heterogeneity

2021 ◽  
Author(s):  
Yanfei Zhang ◽  
Vani C. Movva ◽  
Marc S Williams ◽  
Ming Ta Michael Lee
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Clustering Analysis ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Causal Effect ◽  
Sex Hormone Binding Globulin ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Insulin Resistant ◽  
Disease Outcomes

Purpose Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We attempted to deconstruct the PCOS heterogeneity from a genetic perspective. Methods We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effect of the traits on PCOS and PCOS on disease outcomes. Results Clustering analysis suggested three categories of variants: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in insulin resistant cluster with fasting insulin and glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization supported the causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes. Main Conclusions Our study provides genetic evidence for the heterogeneity in PCOS etiologies, corresponding to the reported phenotypic subtypes. Such studies will improve the current PCOS diagnosis criteria that do not distinguish the heterogeneity. Classification of women with PCOS to inform appropriate treatment will be more accurate in the future with improvements in clustering analysis for PCOS.

scholarly journals A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome

2012 ◽  
Vol 166 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Wei Wei ◽  
Hongmin Zhao ◽  
Aili Wang ◽  
Ming Sui ◽  
Kun Liang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Sex Hormone Binding Globulin ◽  
Metabolic Effects ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Insulin Sensitizer

ObjectivePolycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance (IR). Berberine (BBR) is an isoquinoline derivative alkaloid extracted from Chinese medicinal herbs that has been used as an insulin sensitizer. BBR may have a potential therapeutic value for PCOS. The aim of this study was to evaluate the effects of BBR in comparison to metformin (MET) on the metabolic features of women with PCOS.Design and methodsEighty-nine subjects with PCOS and IR subjects were randomized into one of three treatment groups: BBR+compound cyproterone acetate (CPA; n=31), MET+CPA (n=30), and placebo+CPA (n=28) for 3 months. Clinical characteristics of the women and metabolic and hormonal parameters were assessed before and after the period of treatment.ResultsTreatment with BBR in comparison to MET showed decrease in waist circumference and waist-to-hip ratio (WHR; P<0.01), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC; P<0.05) as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG; P<0.05). Similarly, treatment with BBR in comparison to placebo showed decrease in WHR, fasting plasma glucose, fasting insulin, homeostasis model assessment for IR, area under the curve of insulin, TC, LDLC, and TG (P<0.05) as well as increase in HDLC and SHBG (P<0.01).ConclusionsIntake of BBR improved some of the metabolic and hormonal derangements in a group of treated Chinese women with PCOS. Main effects could be related to the changes in body composition in obesity and dyslipidemia. Further controlled studies are needed for the assessment of the potential favorable metabolic effects of BBR in women with PCOS.

scholarly journals Racial and Ethnic Differences in Metabolic Disease in Adolescents With Obesity and Polycystic Ovary Syndrome

2021 ◽  
Vol 5 (4) ◽  
Author(s):  
Stanley Andrisse ◽  
Yesenia Garcia-Reyes ◽  
Laura Pyle ◽  
Megan M Kelsey ◽  
Kristen J Nadeau ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
General Population ◽  
Polycystic Ovary Syndrome ◽  
Race And Ethnicity ◽  
Polycystic Ovary ◽  
Sex Hormone Binding Globulin ◽  
Oral Glucose ◽  
Model Assessment ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is common and associated with metabolic syndrome. In the general population, metabolic disease varies by race and ethnicity. Objective This work aimed to examine in depth the interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth. Methods A secondary analysis was conducted of data from girls (age 12-21 years) with overweight or obesity (&gt; 90 body mass index [BMI] percentile) and PCOS. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test (OGTT), and magnetic resonance imaging for hepatic fat. Groups were categorized by race or ethnicity. Results Participants included 39 non-Hispanic White (NHW, age 15.7 ± 0.2 years; BMI 97.7 ± 0.2 percentile), 50 Hispanic (HW, 15.2 ± 0.3 years; 97.9 ± 0.3 percentile), and 12 non-Hispanic Black (NHB, 16.0 ± 0.6 years; 98.6 ± 0.4 percentile) adolescents. Hepatic markers of insulin resistance were worse in NHW, including lower sex hormone–binding globulin and higher triglycerides over high-density lipoprotein cholesterol (TGs/HDL-C) ratio (P = .002 overall, HW vs NHB [P = .009] vs NHW [P = 0.020]), although homeostasis model assessment of estimated insulin resistance was worst in NHB (P = .010 overall, NHW vs NHB P = .014). Fasting and 2-hour OGTT glucose were not different between groups, although glycated hemoglobin A1c (HbA1c) was lowest in NHW (overall P &lt; .001, NHW 5.2 ± 0.3 vs HW 5.5 ± 0.3 P &lt; .001 vs 5.7 ± 0.4%, P &lt; .001). The frequency of hepatic steatosis (HW 62%, NHW 42%, NHB 25%, P = .032); low HDL-C &lt; 40 mg/dL (HW 82%, NHW 61%, NHB 50%, P &lt; .001) and prediabetes HbA1c 5.7% to 6.4% (NHB 50%, HW 36%, NHW 5%, P &lt; .001) were different between the groups. Conclusion Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components.

scholarly journals Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome

2021 ◽  
Author(s):  
Qian Sun ◽  
Yuan Gao ◽  
Jingyun Yang ◽  
Jiayi Lu ◽  
Wen Feng ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Whole Blood ◽  
Multiple Testing ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Research Question ◽  
Ovary Syndrome ◽  
Unclear Etiology ◽  
Eqtl Data

Research question: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unclear etiology. Are there any genes that are pleiotropically or potentially causally associated with PCOS? Design: We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for PCOS and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with PCOS. We performed separate SMR analysis using eQTL data in the ovary and whole blood. Results: Although no genes showed significant pleiotropic association with PCOS after correction for multiple testing, some of the genes exhibited suggestive significance. RPS26 showed the strongest suggestive pleiotropic association with PCOS in both SMR analyses (β[SE]=0.10[0.03], PSMR=1.72*10-4 for ovary; β[SE]=0.11[0.03], PSMR=1.40*10-4 for whole blood). PM20D1 showed the second strongest suggestive pleiotropic association with PCOS in the SMR analysis using eQTL data for the whole blood, and was also among the top ten hit genes in the SMR analysis using eQTL data for the ovary. Two other genes, including CTC-457L16.2 and NEIL2, were among the top ten hit genes in both SMR analyses. Conclusion: We identified multiple genes that were potentially involved in the pathogenesis of PCOS. Our findings provided helpful leads to a better understanding of the mechanisms underlying PCOS, and revealed potential therapeutic targets for the effective treatment of PCOS.

scholarly journals Serum concentrations of afamin are elevated in patients with polycystic ovary syndrome

2014 ◽  
Vol 3 (3) ◽  
pp. 120-126 ◽  
Author(s):  
Angela Köninger ◽  
Philippos Edimiris ◽  
Laura Koch ◽  
Antje Enekwe ◽  
Claudia Lamina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
University Hospital ◽  
Sex Hormone Binding Globulin ◽  
Antioxidant Vitamin ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Ovary Syndrome ◽  
Cross Sectional

Oxidative stress seems to be present in patients with polycystic ovary syndrome (PCOS). The aim of this study was to evaluate the correlation between characteristics of PCOS and serum concentrations of afamin, a novel binding protein for the antioxidant vitamin E. A total of 85 patients with PCOS and 76 control subjects were investigated in a pilot cross-sectional study design between 2009 and 2013 in the University Hospital of Essen, Germany. Patients with PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were determined at early follicular phase. Afamin concentrations were significantly higher in patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml increase in afamin=1.3, 95% CI=1.08–1.58). This difference vanished in a model adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding globulin (SHBG) (OR=1.05, 95% CI=0.80–1.38). In patients with PCOS, afamin correlated significantly with homeostatic model assessment-insulin resistance (HOMA-IR), fasting glucose, BMI, FTI, and SHBG (P<0.001), but in a multivariate linear model, only HOMA-IR remained significantly associated with afamin (P=0.001). No correlation was observed between afamin and androgens, LH, FSH, LH/FSH ratio, antral follicle count, ovarian volume, or anti-Müllerian hormone. In conclusion, elevated afamin values may indicate a state of oxidative stress and inflammation, strongly associated with IR and offering an indicator of impaired glucose tolerance in patients with PCOS irrespective of obesity.

scholarly journals Improvement of endothelial function with metformin and rosiglitazone treatment in women with polycystic ovary syndrome

2008 ◽  
Vol 159 (4) ◽  
pp. 399-406 ◽  
Author(s):  
Mojca Jensterle ◽  
Miran Sebestjen ◽  
Andrej Janez ◽  
Janez Prezelj ◽  
Tomaz Kocjan ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Polycystic Ovary ◽  
Early Stage ◽  
Free Testosterone ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Insulin Resistant

ObjectiveThere is evidence of preclinical cardiovascular disease even in young women with polycystic ovary syndrome (PCOS). The aim of our study was to assess and compare the effects of metformin (MET) and rosiglitazone (ROSI) on endothelial function in PCOS patients.MethodsFor 6 months, 26 women with PCOS received either MET or ROSI. Blood samples for assessment of androgens, lipids, and high-sensitive C-reactive protein were taken at baseline and at endpoint. Endothelium-dependent flow-mediated dilation (FMD) and glyceryl trinitrate-induced endothelium-independent dilation of brachial artery were studied before and after treatment. Homeostasis model assessment (HOMAIR) calculation was applied as a measure of insulin resistance (IR).ResultsWith treatment, FMD of brachial artery improved significantly from 4.2±6.6 to 10.2±5.9% in MET group (P=0.036) and from 2.9±3.2 to 7.6±4.9% in ROSI group (P=0.026), MET being as effective as ROSI (P=0.70). The endothelium-independent dilation did not change. Additionally, administration of MET was associated with a significant decrease in HOMAIR (P=0.003), serum total and serum-free testosterone (P=0.045 and P=0.008 respectively) and significantly higher frequencies of menstrual bleeding (P=0.006).ConclusionsA 6-month therapy with insulin sensitizers, MET and ROSI, resulted in marked improvement of endothelial function in young PCOS patients without clinically evident atherosclerosis who were not severely insulin resistant. Neither drug was superior to the other. We conclude that therapeutic intervention with either insulin sensitizer may reverse the atherosclerotic process in PCOS patients at its early stage.

scholarly journals Polymorphisms of TCF7L2 gene in South Brazilian women with polycystic ovary syndrome: a cross-sectional study

2013 ◽  
Vol 169 (5) ◽  
pp. 569-576 ◽  
Author(s):  
Ramon Bossardi Ramos ◽  
Denusa Wiltgen ◽  
Poli Mara Spritzer
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Cross Sectional Study ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Model Assessment ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Ovary Syndrome ◽  
Cross Sectional

ObjectiveTo assess whetherTCF7L2single nucleotide polymorphisms rs7903146 C/T and rs11196236 C/T are associated with polycystic ovary syndrome (PCOS) in South Brazilian women.DesignCross-sectional study.MethodsTwo hundred PCOS patients and 102 non-hirsute, ovulatory controls were genotyped by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using the PHASE 2.1.1 software.Results and conclusionsThe distribution of rs7903146 (PCOS, 54.4% CC; 28.5% CT; 17.1% TT; controls, 51.0% CC; 37.0% CT; 12.0% TT) and rs11196236 (PCOS, 4.3% CC; 33.5% CT; 62.2% TT; controls, 3.2% CC; 35.5% CT; 61.3% TT) was similar between the groups. rs7903146 and rs11196236 were not in linkage disequilibrium (|D′|=0.34;r2=0.07). PCOS participants were younger, with higher age-adjusted BMI, waist circumference, blood pressure, triglycerides, insulin, homeostasis model assessment index to estimate insulin resistance and total testosterone, and lower HDL-C and sex hormone binding globulin vs controls. In PCOS, no differences between genotypes and haplotypes were found for clinical and metabolic variables. However, for each T (rs7903146) and T (rs11196236) allele added to the haplotypes, a variation of 5.87 cm in waist (Ptrend=0.01), 10.7 mg/dl in total cholesterol (Ptrend=0.03), and 10.3 mg/dl in LDL-C (Ptrend=0.01) was recorded.TCF7L2variants are probably not implicated in PCOS development in South Brazilian women.

Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life

2019 ◽  
Vol 17 (5) ◽  
pp. 455-464 ◽  
Author(s):  
Alfonso Mate ◽  
Antonio J. Blanca ◽  
Rocío Salsoso ◽  
Fernando Toledo ◽  
Pablo Stiefel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Insulin Therapy ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Resistant ◽  
Hypertensive Disorders ◽  
The Impact ◽  
In Pregnancy

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

scholarly journals Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Confidence Interval ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Meta Analysis ◽  
Mean Difference ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Synbiotic Supplementation

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.

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