Metabolic consequences of obesity on the hypercoagulable state of polycystic ovary syndrome

AbstractPolycystic ovary syndrome (PCOS) women have a hypercoagulable state; however, whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. We determined plasma coagulation pathway protein levels in PCOS (n = 146) and control (n = 97) women recruited to a PCOS biobank. Circulating levels of a panel of 18 clotting pathway proteins were determined by Slow Off-rate Modified Aptamer-scan plasma protein measurement. Cohorts were age matched, though PCOS had elevated body mass index (p < 0.001), insulin (p < 0.001) and C-reactive protein (CRP) (p < 0.0001). Eight pro-coagulation proteins were elevated in PCOS: plasminogen activator inhibitor-1 (p < 0.0001), fibrinogen (p < 0.01), fibrinogen gamma chain (p < 0.0001), fibronectin (p < 0.01), von Willebrand factor (p < 0.05), D-dimer (p < 0.0001), P-selectin (p < 0.05), and plasma kallikrein (p < 0.001). However, two anticoagulant proteins, vitamin K-dependent protein-S (p < 0.0001) and heparin cofactor-II (p < 0.001) were elevated and prothrombin was decreased (p < 0.05). CRP, as a marker of inflammation, and insulin resistance (HOMA-IR) correlated with 11 and 6 of the clotting proteins, respectively (p < 0.05). When matched for BMI < 25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p < 0.05) and heparin cofactor-II was increased (p < 0.05). In a multivariate analysis accounting for inflammation, insulin resistance and BMI, there was no correlation of PCOS with any of the coagulation proteins. The hypercoagulable state in PCOS is not intrinsic to the disease as it can be fully accounted for by BMI, inflammation and insulin resistance.

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Metabolic Consequences Of Obesity On The Hypercoagulable State Of Polycystic Ovary Syndrome: A Risk For Severe SARS-Cov-2 Infection?

10.21203/rs.3.rs-76784/v1 ◽

2020 ◽

Author(s):

Abu Saleh Md M ◽

Thozhukat Sathyapalan ◽

Ilhame Diboun ◽

Mohamed Elrayess ◽

Alexandra E Butler ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Hypercoagulable State ◽

Plasminogen Activator Inhibitor 1 ◽

Gamma Chain ◽

Heparin Cofactor Ii ◽

Ovary Syndrome ◽

Metabolic Complications ◽

Coagulation Proteins

Abstract Introduction: Polycystic ovary syndrome (PCOS) women have a hypercoagulable state and are also at high risk for severe COVID-19 leading to thromboembolic complications and increased mortality; however, whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. Methods: We determined plasma coagulation pathway protein levels in PCOS (n=146) and control (n=97) women recruited to a PCOS biobank. Circulating levels of a panel of 18 clotting pathway proteins were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement.Results: Cohorts were age matched, though PCOS had elevated body mass index (BMI)(p<0.001), insulin (p<0.001) and C-reactive protein (CRP)(p<0.0001). Eight pro-coagulation proteins were elevated in PCOS: plasminogen activator inhibitor-1 (PAI-1)(p<0.0001), fibrinogen (p<0.01), fibrinogen gamma chain (p<0.0001), fibronectin (p<0.01), von Willebrand factor (p<0.05), D-dimer (p<0.0001), P-selectin (p<0.05), and plasma kallikrein (p<0.001). However, two anticoagulant proteins, vitamin K-dependent protein-S (p<0.0001) and heparin cofactor-II (p<0.001) were elevated and prothrombin was decreased (p<0.05). CRP, as a marker of inflammation, and insulin resistance (HOMA-IR) correlated with 11 and 6 of the clotting proteins, respectively (p<0.05). When matched for BMI<25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p<0.05) and heparin cofactor-II was increased (p<0.05). In a multivariate analysis accounting for inflammation, insulin resistance and BMI, there was no correlation of PCOS with any of the coagulation proteins.Conclusion: The hypercoagulable State in PCOS can be fully accounted for by BMI, inflammation and insulin resistance suggesting that only obese PCOS women would be predisposed to an enhanced risk for severe COVID-19-related disease.

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Biomediators in Polycystic Ovary Syndrome and Cardiovascular Risk

Biomolecules ◽

10.3390/biom11091350 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1350

Author(s):

Srdan Pandurevic ◽

Djuro Macut ◽

Flaminia Fanelli ◽

Uberto Pagotto ◽

Alessandra Gambineri

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Molecular Mechanisms ◽

Polycystic Ovary ◽

Clinical Manifestations ◽

Molecular Heterogeneity ◽

Ovary Syndrome ◽

Metabolic Complications ◽

Early Predictors ◽

Cv Disease

Polycystic ovary syndrome (PCOS) is extremely heterogeneous in terms of clinical manifestations. The variability of the syndrome’s phenotype is derived from the genetic and molecular heterogeneity, with a great deal of environmental factors that may have long-term health consequences, such as metabolic and cardiovascular (CV) diseases. There is no doubt that women with PCOS suffer from metabolic complications more than their age-matched counterparts in the general population and at an earlier age. Obesity, low steroid hormone-binding globulin (SHBG), hyperandrogenemia, insulin resistance, and compensatory hyperinsulinemia are biomediators and early predictors of metabolic complications in PCOS. Doubts remain about the real risk of CV diseases in PCOS and the molecular mechanisms at the basis of CV complications. Based on that assumption, this review will present the available evidence on the potential implications of some biomediators, in particular, hyperandrogenism, estrogen-progesterone imbalance, insulin resistance, and low SHBG, in the processes leading to CV disease in PCOS, with the final aim to propose a more accurate CV risk assessment.

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SAT-627 Racial and Ethnic Differences in Metabolic Disease in Obese Adolescents with Polycystic Ovary Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1922 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Stanley Andrisse ◽

Yesenia Garcia Reyes ◽

Laura Pyle ◽

Kristen Nadeau ◽

Megan Moriarty Kelsey ◽

...

Keyword(s):

Metabolic Disease ◽

Insulin Resistance ◽

General Population ◽

Polycystic Ovary Syndrome ◽

Hepatic Steatosis ◽

Race And Ethnicity ◽

Polycystic Ovary ◽

Hispanic Youth ◽

Ovary Syndrome ◽

Metabolic Complications

Abstract Background: Polycystic ovary syndrome (PCOS) affects up to 15% of women and is associated with a multitude of metabolic complications including insulin resistance, type 2 diabetes, cardiovascular disease, and hepatic steatosis. In the general population, metabolic disease rates vary by race and ethnicity. The interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth has not been extensively examined. Methods: Secondary analysis of data from overweight and obese (>90 BMI%ile) adolescent (12-21 years) female participants with PCOS enrolled across 4 protocols. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test and MRI for hepatic fat. Groups were compared by ANOVA, with and without correction for BMI or chi-square tests for proportions. Results: Participants included 39 white (NHW 15.7±0.2 years; 97.7±0.2 BMI%ile), 50 Hispanic (15.2±0.3 years; 97.9±0.3 BMI%ile) and 12 black (NHB 16.0±0.6 years; 98.6±0.4 BMI%ile) adolescents. BMI%ile was different between groups (p=0.04), but age of menarche, free testosterone and hirsutism severity were not. Hepatic markers of insulin resistance were worse in Hispanic youth, including lower sex hormone binding globulin and TG/HDL ratio (p<0.001), although HOMA-IR was worst in NHB (p=0.009) and Hispanic (p=0.036) compared to NHW youth. There were no significant differences in insulin concentrations—either fasting or during the OGTT—although fasting C-peptide was higher in Hispanic (p=0.008) compared to NHW youth. Fasting and 2-hour glucose concentrations were not different between groups. HbA1c was highest in NHB (5.7±0.4%, p<0.001 vs. NHW, p=0.026 vs. Hispanic), then Hispanic (5.5±0.3, p<0.001 vs. NHW), then NHW (5.2±0.3) youth. Fasting triglycerides differed between groups (p=0.029), being highest in Hispanic youth (129 [105,167] mg/dL). The frequency of hepatic steatosis (NHW 42%, Hispanic 62% NHB 25%, p=0.032) and the metabolic syndrome components HDL <40 mg/dL (NHW 61%, Hispanic 82% NHB 50%, p<0.001) and HbA1c 5.7-6.4% (NHW 5%, Hispanic 36% NHB 50%, p<0.001) were different between the groups. Conclusions: Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components.

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Effects of Mixed of a Ketogenic Diet in Overweight and Obese Women with Polycystic Ovary Syndrome

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182312490 ◽

2021 ◽

Vol 18 (23) ◽

pp. 12490

Author(s):

Raffaele Ivan Cincione ◽

Francesca Losavio ◽

Fabiana Ciolli ◽

Anna Valenzano ◽

Giuseppe Cibelli ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Ketogenic Diet ◽

Polycystic Ovary ◽

Therapeutic Option ◽

Significant Risk ◽

Obese Women ◽

Ovary Syndrome ◽

Metabolic Complications

Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid with insulin resistance, dyslipidemia, and obesity, it also carries significant risk for the development of cardiovascular and metabolic sequelae, including diabetes and metabolic syndrome. The relationship between central obesity and the development of insulin resistance is widely verified. Adipose tissue excess and the coexistent dysregulation of adipocyte functions directly contribute to the pathogenesis of the metabolic complications observed in women with PCOS. In the light of these evidence, the most therapeutic option prescribed to obese women with PCOS, regardless of the phenotype e from the severity of clinical expression, is lifestyle correction by diet and physical activity. The aim of this study is to evaluate the beneficial effects of ketogenic diet in 17 obese women with PCOS. Our results showed that the ketogenic diet inducing therapeutic ketosis, improves the anthropometric and many biochemical parameters such as LH, FSH, SHBG, insulin sensitivity and HOMA index. In addition, it induces a reduction in androgenic production, whereas the contextual reduction of fat mass reduced the acyclic production of estrogens deriving from the aromatization in the adipose tissue of the androgenic excess, with an improvement of the LH/FSH ratio. This is the first study on the effects of the ketogenic diet on PCOS, however, further studies are needed to elucidate the mechanism underlying ketogenic diet effects.

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Treatment of adolescent girls with polycystic ovary syndrome and insulin resistance

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2018-2-13-20 ◽

2018 ◽

Vol 17 (2) ◽

pp. 13-20

Author(s):

E. M. Bogatyreva ◽

G. A. Novik

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Adolescent Girls ◽

Ethinyl Estradiol ◽

Polycystic Ovary ◽

Reproductive Age ◽

Ovary Syndrome ◽

Metabolic Complications ◽

Study Results ◽

Oral Preparation

Aim. Polycystic ovary syndrome is a common cause of infertility. In addition, polycystic ovary syndrome is often associated with metabolic complications. In most women hyperandrogenic manifestations occur during puberty. Early detection of polycystic ovary syndrome and associated metabolic problems can solve the problem of puberty and prevent infertility, metabolic syndrome, and diabetes mellitus type 2 in women of reproductive age. One of the objectives of the study was to evaluate the effectiveness of the simultaneous use of a combined oral preparation (ethinyl estradiol + drospirenone) and metformin in adolescent girls with polycystic ovary syndrome.Materials and methods. 113 adolescent girls with hyperandrogenism from 14 to 19 years were included. 32 of these girls aged 14–18 years with polycystic ovary syndrome were treated with medication ethinyl estradiol + drospirenone. Of these 32 patients, 20 girls with insulin resistance were obtained simultaneously with metformin. The following methods were used: examination, evaluation of hair (Ferriman-Gallwey score), pelviс ultrasound, determination of hormone status (LH, FSH, PRL, 17-OHP, E2 , TSH, DHEA-s, SHBG, T), glucose, insulin, and glucose tolerance test. The diagnostic technique used the Sultan C. criteria of polycystic ovary syndrome (2004).Results.A reduction in the frequency characteristics after treatment was shown: of laboratory hyperandrogenism 90.6% , dermopathy 65.6% , insulin resistance 43.8%, hyperinsulinemia 18.8%, ultrasonic signs of PCOS 34.4%.Conclusions. The study results confirm the efficacy of the treatment of polycystic ovary syndrome with insulin resistance during puberty by Low-dose combined oral preparation (0.03 mg ethinyl estradiol and 3 mg drospirenone) in combination with metformin.

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Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges

Nutrition Research Reviews ◽

10.1017/s0954422416000287 ◽

2017 ◽

Vol 30 (1) ◽

pp. 97-105 ◽

Cited By ~ 21

Author(s):

Yvonne M. Jeanes ◽

Sue Reeves

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Advanced Glycation Endproducts ◽

Primary Therapy ◽

Lifestyle Modifications ◽

Ovary Syndrome ◽

Metabolic Complications ◽

Methodological Challenges ◽

Increased Risk

AbstractWomen with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.

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