scholarly journals The Association Between Genetically Predicted Systemic Inflammatory Regulators and Polycystic Ovary Syndrome: A Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanxiao Chen ◽  
Yaoyao Zhang ◽  
Shangwei Li ◽  
Yuanzhi Tao ◽  
Rui Gao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Mendelian Randomization ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Reproductive Age ◽  
European Ancestry ◽  
Ovary Syndrome ◽  
Increased Risk

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases among women of reproductive age. Inflammation may be involved in the pathogenesis of PCOS, but its exact relationship with PCOS remains unclear. Herein, we investigate the causal association between systemic inflammatory regulators and PCOS risk through a two-sample Mendelian randomization (MR) approach based on the latest and largest genome-wide association study (GWAS) of 41 systemic inflammatory regulators in 8293 Finnish participants and a GWAS meta-analysis consisting of 10,074 PCOS cases and 103,164 controls of European ancestry. Our results suggest that higher levels of IL-17 and SDF1a, as well as lower levels of SCGFb and IL-4, are associated with an increased risk of PCOS (OR = 1.794, 95% CI = 1.150 – 2.801, P = 0.010; OR = 1.563, 95% CI = 1.055 – 2.315, P = 0.026; OR = 0.838, 95% CI = 0.712 – 0.986, P = 0.034; and OR = 0.637, 95% CI = 0.413 – 0.983, P = 0.042, respectively). In addition, genetically predicted PCOS is related to increased levels of IL-2 and VEGF (OR = 1.257, 95% CI = 1.022 – 1.546, P = 0.030 and OR = 1.112, 95% CI = 1.006 – 1.229, P = 0.038, respectively). Our results indicate the essential role of cytokines in the pathogenesis of PCOS. Further studies are warranted to assess the possibility of these biomarkers as targets for PCOS prevention and treatment.

scholarly journals Relationships Between Biochemical Markers of Hyperandrogenism and Metabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 51 (01) ◽  
pp. 22-34 ◽  
Author(s):  
Mina Amiri ◽  
Fahimeh Tehrani ◽  
Razieh Bidhendi-Yarandi ◽  
Samira Behboudi-Gandevani ◽  
Fereidoun Azizi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Polycystic Ovary Syndrome ◽  
Biochemical Markers ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Metabolic Parameters ◽  
High Density Lipoproteins ◽  
Total Testosterone ◽  
Ovary Syndrome ◽  
Increased Risk

AbstractWhile several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=–0.009; 95% CI: –0.02, –0.001), and systolic blood pressure (SBP) (β=–0.01; 95% CI: –0.03, –0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=–0.41; 95% CI: –0.70, –0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=–0.03; 95% CI: –0.06, –0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.

scholarly journals Phenotypic clustering reveals distinct subtypes of polycystic ovary syndrome with novel genetic associations

2019 ◽  
Author(s):  
Matthew Dapas ◽  
Frederick T. J. Lin ◽  
Girish N. Nadkarni ◽  
Ryan Sisk ◽  
Richard S. Legro ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Diagnostic Criteria ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
European Ancestry ◽  
Sequencing Analysis ◽  
Ovary Syndrome ◽  
Biologically Relevant ◽  
Insulin Levels ◽  
Family Based

AbstractBackgroundPolycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes. We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS.Methods and FindingsUnsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped discovery cohort of 893 PCOS cases and an ungenotyped validation cohort of 263 PCOS cases. We identified two PCOS subtypes: a “reproductive” group (21-23%) characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low body mass index (BMI) and insulin levels; and a “metabolic” group (37-39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels. We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes. We identified alleles in four novel loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN1, P=2.2×10-10; IQCA1, P=2.8×10-9; BMPR1B/UNC5C, P=9.7×10-9; CDH10, P=1.2×10-8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P=1.0×10-8). We have previously reported that rare variants in DENND1A, a gene regulating androgen biosynthesis, were associated with PCOS quantitative traits in a family-based whole genome sequencing analysis. We classified the reproductive and metabolic subtypes in this family-based PCOS cohort and found that the subtypes tended to cluster in families and that carriers of rare DENND1A variants were significantly more likely to have the reproductive subtype of PCOS. Limitations of our study were that only PCOS cases of European ancestry diagnosed by NIH criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated.ConclusionsIn conclusion, we have found stable reproductive and metabolic subtypes of PCOS. Further, these subtypes were associated with novel susceptibility loci. Our results suggest that these subtypes are biologically relevant since they have distinct genetic architectures. This study demonstrates how precise phenotypic delineation can be more powerful than increases in sample size for genetic association studies.

scholarly journals Update on polycystic ovary syndrome

2021 ◽  
Author(s):  
Jin Ju Kim
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Daily Practice ◽  
Antral Follicle ◽  
Reproductive Age ◽  
Lifestyle Modifications ◽  
First Line ◽  
Ovary Syndrome ◽  
Wide Range

Polycystic ovary syndrome (PCOS) is a common disorder in reproductive-age women. In 2018, an international evidence-based guideline announced recommendations spanning a wide range of issues on the assessment and management of PCOS. From the 166 recommendations, the present study reviews those that are of particular clinical relevance for daily practice and introduces other relevant studies that have been published since the global guideline. The 2018 guideline increased the antral follicle count cutoff for the diagnosis of PCOS from 12 to 20 when using a high-frequency probe. Hirsutism was defined as having a score of ≥4–6 based on a lower percentile of 85%–90% or cluster analysis, which was lower than the traditionally used 95th percentile-based cutoff. The diagnosis of PCOS in adolescents is challenging, and irregular menstruation was defined carefully according to years from menarche. The use of ultrasonography for the diagnosis of PCOS was restricted to those 8 years after menarche. As medication for non-fertility indications, combined oral contraceptives are the first-line drug. Metformin, in addition to lifestyle modifications, should be considered for adult patients with a body mass index ≥25 kg/m2 for the management of weight and metabolic outcomes. An aromatase inhibitor is the recommended first-line medication for ovulation induction, a subsequent individual patient data meta-analysis also reported the same conclusion. Whether the new global guideline will be fully adopted by many specialists and change clinical practice is open to question. Further studies are needed to better understand and manage PCOS patients well.

scholarly journals Endometrium and polycystic ovary syndrome

2018 ◽  
Vol 67 (4) ◽  
pp. 60-66
Author(s):  
Pavel P Yakovlev ◽  
Igor Yu Kogan
Keyword(s):  
Endometrial Cancer ◽  
Polycystic Ovary Syndrome ◽  
Pregnancy Outcomes ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Endocrine Disorder ◽  
Increased Risk ◽  
Adverse Pregnancy

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Patients with PCOS present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS is inconsistently associated adverse pregnancy outcomes and an increased risk of endometrial cancer. The purpose of this review is to systematize the available data on endometrial dysfunction associated with PCOS. (For citation: Yakovlev PP, Kogan IYu. Endometrium and polycystic ovary syndrome. Journal of Obstetrics and Women’s Diseases. 2018;67(4):60-66. doi: 10.17816/JOWD67460-66).

scholarly journals Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: Study Protocol for a Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Jinjin Gao ◽  
Wei Li ◽  
Yangyang Li ◽  
Yan Li
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Reproductive Age ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Complementary And Alternative Therapy

Abstract Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. As a widely used complementary and alternative therapy, acupuncture is increasingly used to treat PCOS. However, the effect of acupuncture in treating PCOS is uncertain and the mechanisms are unclear. This systematic review aims to determine the efficacy of acupuncture on PCOS in animal preclinical models.Methods: We will search the following databases: PubMed, Web of Science, China National Knowledge Infrastructure and Chinese Science and Technology Periodical Database. We will only include animal experiments of acupuncture in treating PCOS. The primary outcome will be homeostatic model assessment- insulin resistance. The risk of bias will be assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. Confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. All meta-analyses will be conducted using Review Manager 5.4. Discussion: To the best of our knowledge, the use of acupuncture in treating PCOS has not yet been systematically reviewed in animal models. The evidence generated from this systematic review and meta-analysis could benefit future researches. Systematic review registration: OSF (Registration DOI: 10.17605/OSF.IO/FNM37)

scholarly journals A study of metabolic syndrome in women with polycystic ovary syndrome at tertiary care center

2021 ◽  
Vol 10 (6) ◽  
pp. 2427
Author(s):  
Chelsae Kuntal ◽  
Jyotsna Vyas ◽  
Asha Chaudhary ◽  
Sunita Hemani ◽  
Lata Rajoria
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Urban Areas ◽  
Polycystic Ovary ◽  
Tertiary Care ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Hormonal Profile ◽  
Increased Risk

Background: Polycystic ovary syndrome is a common endocrinopathy in women of reproductive age with prevalence of 6-10% which is characterized by hyper androgenic features and chronic oligo – anovulation and polycystic ovary morphology. Most women with polycystic ovary syndrome are also characterized by metabolic abnormalities like insulin resistance, hyperinsulinemia, dyslipidemia and abdominal obesity, these forming risk factors for metabolic syndrome. The objective of the study was to compare the clinical, biochemical and hormonal profile of polycystic ovary syndrome patients with and without metabolic syndrome.Methods: A comparative cross- sectional study was undertaken on 79 PCOS women diagnosed with PCOS according to Rotterdam criteria, in which the clinical data and hormonal profile of two groups of polycystic ovary syndrome women with and without metabolic syndrome was compared.Results: The mean age of 79 patients in this study group with and without metabolic syndrome was 26.17±3.18 and 25.57±3.41 years respectively. There were more patients from urban areas as compared to rural areas and maximum patients. Significantly higher number of PCOS women with metabolic syndrome had hirsutism and acanthosis nigricans than those without metabolic syndrome. Mean value of Waist circumference, systolic BP pressure, diastolic BP, S. Triglyceride and fasting glucose were higher and HDL levels were lower in women with metabolic syndrome than those without metabolic syndrome. Fasting insulin and HOMA-IR values were significantly higher in PCOS women with metabolic syndrome in comparison to those without metabolic syndrome.Conclusion: PCOS is not only is the most frequent cause of anovulation, but it is also associated with characteristic metabolic disturbances that may have important implications for the long term health. Metabolic syndrome is a cluster of endocrine disturbances, including insulin resistance, dyslipidemia, obesity, and hypertension. It is associated with a two-fold increased risk of cardiovascular disease and a five-fold increased risk of type 2 diabetes. This illustrates the importance of early detection of insulin resistance and metabolic syndrome with subsequent application of preventive measures in women with polycystic ovary syndrome.

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 Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. R219-R227 ◽  
Author(s):  
Poli Mara Spritzer ◽  
Sheila B Lecke ◽  
Fabíola Satler ◽  
Debora M Morsch
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Lifestyle Changes ◽  
Reproductive Age ◽  
Sufficient Evidence ◽  
Low Grade ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Increased Risk

Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

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