Sympathetic activation and endothelial dysfunction in polycystic ovary syndrome are not explained by either obesity or insulin resistance

2015 ◽  
Vol 83 (6) ◽  
pp. 812-819 ◽  
Author(s):  
Elisabeth A. Lambert ◽  
Helena Teede ◽  
Carolina Ika Sari ◽  
Eveline Jona ◽  
Soulmaz Shorakae ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Sympathetic Activation ◽  
Ovary Syndrome

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

Cardiovascular disease risk in the siblings of women with polycystic ovary syndrome

2019 ◽  
Vol 34 (8) ◽  
pp. 1559-1566 ◽  
Author(s):  
Subramaniam Karthik ◽  
V P Vipin ◽  
Aditya Kapoor ◽  
Archana Tripathi ◽  
Manoj Shukla ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Asian Indian ◽  
Polycystic Ovary ◽  
Tertiary Care ◽  
Metabolic Risk ◽  
Cvd Risk ◽  
Ovary Syndrome

Abstract STUDY QUESTION Do the siblings of Asian Indian women with polycystic ovary syndrome (PCOS) manifest increased cardiovascular disease (CVD) risk by carotid intima-media thickness (CIMT) and brachial artery flow-mediated dilatation (FMD)? SUMMARY ANSWER Siblings had functional endothelial dysfunction (FMD was reduced) when compared to age and BMI-matched controls while sisters but not brothers had structural endothelial dysfunction (CIMT was increased). WHAT IS KNOWN ALREADY Siblings of women with PCOS have increased metabolic risk but it varies with ethnicity. Among Asian Indians the only previous study has shown reduced FMD in brothers. STUDY DESIGN, SIZE, DURATION This study was a tertiary care hospital-based cross-sectional case control study in the outpatient department of the endocrine clinic over 18 months. In total, 41 brothers and 35 sisters of women with PCOS (diagnosed by 2003 Rotterdam criteria) were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS Age (±2 years), sex and BMI- (±1 kg/m2) matched controls were selected. Cases and controls underwent clinical and biochemical investigations. Cardiologists performed doppler ultrasonogram to determine CIMT and FMD in a blinded fashion. MAIN RESULTS AND THE ROLE OF CHANCE FMD was decreased in brothers [median 12.3% interquartile range (5.1, 19) versus 18.4% (12.6, 21.5), P = 0.002] and in sisters [10.8% (5.8, 17.2) versus 14.7% (11.4, 18.2), P = 0.027] when compared to controls. CIMT was higher in sisters [median 0.4 mm (0.35, 0.5) versus 0.3 mm (0.3, 0.4), P= 0.002] when compared to controls but not in brothers. Metabolic syndrome was more common in brothers (27% versus 5% in controls, P = 0.007) even after matching for age and BMI. Insulin resistance (homeostatic model assessment for insulin resistance and acanthosis) was higher in brothers as compared to controls. Dehydroepiandrosterone sulphate was significantly elevated in brothers. LIMITATIONS, REASONS FOR CAUTION There may have been referral bias of patients with PCOS in a tertiary care institute, and the radiological assessment was performed by two cardiologists serially on different time frames over the study duration. Power was only 50% in CIMT for brothers. WIDER IMPLICATIONS OF THE FINDINGS Siblings of women with PCOS had higher CVD risk over and above the already pre-existing higher metabolic risk associated with Asian Indian ethnicity and therefore the siblings require vigilant management. Endothelial dysfunction and insulin resistance seems to be a heritable trait of PCOS independent of obesity, which if confirmed in other ethnicities would have important implications. STUDY FUNDING/COMPETING INTEREST(S) Funded by Intramural Research Grant (PGI/DIR/RC/943/2013) from the Sanjay Gandhi Postgraduate Institute of Medical Sciences. No competing interests.

Hypertension in Polycystic Ovary Syndrome: Novel Insights

2020 ◽  
Vol 16 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Djuro Macut ◽  
Violeta Mladenović ◽  
Jelica Bjekić-Macut ◽  
Sarantis Livadas ◽  
Olivera Stanojlović ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ppar Gamma ◽  
Reproductive Age ◽  
Angiotensin Ii Receptor ◽  
Ovary Syndrome ◽  
Increased Risk

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women during reproductive age. It was shown that PCOS women are with high risk for dyslipidemia, glucose intolerance, type 2 diabetes and metabolic syndrome. These factors are considered to represent traditional risk factors for the occurrence of cardiovascular disease. Observed increased risk for hypertension in PCOS women seems to be associated with insulin resistance and hyperinsulinemia. Both conditions interfere with the endothelium-dependent vasodilatation mechanisms causing vascular muscle wall hypertrophy. Obesity and insulin resistance are considered key factors for the alteration of blood pressure in PCOS women. Higher cardiovascular risk is implicated in PCOS with aging and its consequent association with both systolic and diastolic blood pressure. The elements of renin-angiotensin-aldosterone system (RAAS) have an impact on endothelial dysfunction as a marker of cardiovascular damage that could be modified is women with PCOS. Androgens and components of RAAS are involved in the process of atherogenesis in PCOS women. Therefore, it is hypothesized that spironolactone treatment could ameliorate endothelial dysfunction in PCOS women. Recently it was shown that telmisartan, angiotensin II receptor antagonist poses insulinsensitizing capacity to activate PPAR gamma and mediate favorable metabolic and reproductive effects in hypertensive PCOS women.

Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction

2011 ◽  
Vol 164 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Carmen Emanuela Pepene ◽  
Ioana Rada Ilie ◽  
Ioan Marian ◽  
Ileana Duncea
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Nuclear Factor Κb ◽  
Model Assessment ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Ovary Syndrome ◽  
Receptor Activator

ObjectiveThere is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury.DesignA cross-sectional, observational study.MethodsHormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry.ResultsOPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E2) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E2/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG.ConclusionsIn PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.

Oxidative stress markers in women with polycystic ovary syndrome without insulin resistance

2018 ◽  
Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oxidative Stress Markers ◽  
Ovary Syndrome ◽  
Stress Markers
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