Endothelial Dysfunction In Polycystic Ovary Syndrome Research Articles

POLİKİSTİK OVER SENDROMUNDA (PKOS) ENDOTELYAL DİSFONKSİYONUN ERKEN SERUM BELİRTECİ: ENDOCAN

Objective: Polycystic ovary syndrome (PCOS) is a common endocrinological disease in women of reproductive age and has a wide range of metabolic effects. Chronic low-grade inflammation and endothelial dysfunction plays a key role in the pathogenesis of PCOS and they are associated with an increased risk of cardiovascular disease. Endocan, is an inflammatory marker showing endothelial dysfunction. The aim of our study, to compare serum endocan levels in PCOS and healthy control groups and to determine the relationship between some cardiovascular risk factors and serum endocan levels. Materials and Methods: This case-control study included 52 PCOS patients and 59 age-matched healthy controls. Patients were diagnosed as PCOS based on 2003 Rotterdam criteria. Demographic data, history of menstrual irregularity and infertility, polycystic ovary appearance in ultrasonography and hirsutism status were recorded. Endocan levels of PCOS patients and controls were compared. Data analysis was performed by using SPSS-22 for Windows (Statistical Package for Social Science, SPSS Inc. Chicago IL, USA®Z). Results: The median (IQR) value of serum endocan level was 420.7 ng/L (355.2-570.3) in the PCOS group and 320.0 ng/L (219.9-455.9) in the control group (p=0,003). While there was no significant correlation between serum endocan and some cardiovascular risk factors such as waist circumference, hip circumference, BMI, LDL, triglyceride, systolic and diastolic arterial tension but a positive correlation was found between homeostatic model assessment insulin resistance (HOMA-IR) (r= 0.276, p= 0,003). Conclusion: Serum endocan levels are higher in PCOS patients, in line with the literature. Endocan level shows a significant correlation with insulin resistance, one of the metabolic parameters. This may be a sign of early endothelial dysfunction in PCOS.

Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1

The aims of this study were to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), paraoxonase-1(PON-1) and hydroperoxide (LOOH) levels are altered in women with polycystic ovary syndrome (PCOS) and also to determine if hyperandrogenism, insulin resistance (IR) and Anti-Müllerian Hormone (AMH) are associated with endothelial dysfunction in PCOS. A total of 46 women with PCOS and 46 non-PCOS healthy controls were recruited. Women with PCOS had significantly higher sLOX-1, oxLDL and LOOH concentrations than non-PCOS women [6.16 (3.92−13.95) vs 1.37 (0.63−4.43) ng/mL, p < 0.001; 6.48 ± 1.03 vs 3.16 ± 1.02 μU/L, p < 0.001; 2.45 (1.45−3.45) vs 1.06 (0.64−1.56) μmol/L, p < 0.001]. The mean PON-1 level of PCOS group was lower than non-PCOS group (69.47 ± 10.75 vs 104.08 ± 21.43 U/mL, p < 0.001). There was no significant difference in terms of the sLOX-1, oxLDL, LOOH and PON-1 levels between normal weight and overweight PCOS women. On univariate logistic regression analysis, Ferriman-Gallwey scale (FGS), HOMA-IR and AMH were an independent predictors of high risk group of endothelial dysfunction markers (HR-EDm). Age and BMI were not associated with HR-EDm. When incorporated into the multivariate model, endotelial dysfunction markers independently correlated with clinical hyperandrogenism (FGS) but not with AMH. In conclusion, our results indicated that an increased concentration of sLOX-1 might be an early predictor of endothelial damage in patients with PCOS. Women with PCOS have elevated sLOX-1, oxLDL, LOOH and decreased PON-1 levels, independent of BMI. Endothelial dysfunction in women with PCOS is associated with hyperandrogenism. Further studies are required to confirm our findings.

Biomarkers of Endothelial Dysfunction in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. The criteria required for the diagnosis identify various phenotypes, with different reproductive, metabolic, and cardiovascular (CV) risk characteristics. Emerging evidence links adipocyte-secreted hormones as candidates in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors. The aim of this review was to collect, analyze, and qualitatively resynthesize evidence on biomarkers of endothelial dysfunction (visfatin, vascular endothelial growth factor [VEGF], matrix metalloproteinase 9 [MMP-9]) in women with PCOS. Women with PCOS exhibit (a) increased plasma visfatin concentrations compared with controls with a similar body mass index; (b) increased VEGF production along with chronic, mild inflammation; and (c) increased MMP-9 concentrations, which might be related to either excessive CV risk or abnormalities of ovarian extracellular matrix remodeling, multiple cyst formation, follicular atresia, and chronic anovulation. As PCOS has been associated with CV risk, early identification of endothelial dysfunction is clinically relevant.

Serum levels of fibronectin in obese and non-obese women with polycystic ovary syndrome

Aim — to investigate serum level of fibronectin in obese and non-obese women with polycystic ovary syndrome (PCOS) as a marker of endothelial dysfunction, and the relationship of that factor to the endothelium-dependent dilatation and other risk factors for cardiovascular disease.Material and methods. We study 62 women: 45 — with PCOS (23 obese women, 22 — non-obese) and 20 — a control group. Serum level of fibronectin was determined by ELISA. Endothelium-dependent dilatation was measured by test of Celermajer. Data was presented as mean ± SD.Results. We found an elevation of serum level of fibronectin in obese women with PCOS compared to control (258,12±48,47 and 196,34±46,68 pmol/ml respectively; р&lt;0,05), in non-obese women compared to control (227,62±35,36 and 196,34±46,68 pmol/ml respectively, р&lt;0,05). Serum level of fibronectin in obese was higher than non-obese women (258,12±48,47 и 227,62±35,36 pmol/ml respectively, р&lt;0,05). Also, there are a correlation between the serum levels of fibronectin and BMI, HOMA index, lipid metabolism, androgens in PCOS women obese and non-obese (p&lt;0,05).Conclusion. Serum level of fibronectin is elevated in obese and non-obese women with PCOS. Hyperandrogenemia, dyslipidemia, insulin resistence, obesity appears to be significant factor to contributing elevation of fibronectin. The revealed change of fibronectin could reflect an endothelial dysfunction in PCOS.

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

Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturbance or whether they are independently related to PCOS. We examined multiunit and single-unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis) and endothelial function [ischaemic reactive hyperaemia index (RHI) using the EndoPAT device] in 19 overweight/obese women with PCOS (BMI: 31·3 ± 1·5 kg/m(2), age: 31·3 ± 1·6 years) and compared them with 21 control overweight/obese women (BMI: 33·0 ± 1·4 kg/m(2), age: 28·2 ± 1·6 years) presenting a similar metabolic profile (fasting total, HDL and LDL cholesterol, glucose, triglycerides, insulin sensitivity and blood pressure). Women with PCOS had elevated multiunit muscle SNS activity (41 ± 2 vs 33 ± 3 bursts per 100 heartbeats, P < 0·05). Single-unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes (P < 0·01 for all parameters). Women with PCOS also had impaired endothelial function (RHI: 1·77 ± 0·14 vs 2·18 ± 0·14, P < 0·05). HRV did not differ between the groups. Women with PCOS have increased sympathetic drive and impaired endothelial function independent of obesity and metabolic disturbances. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6years, 36±5kg/m2) and 16 control women (31±8years, 30±6kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0-7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4-6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.

Ethinylestradiol30μg-drospirenone and metformin: could this combination improve endothelial dysfunction in polycystic ovary syndrome?

BackgroundWe are hereby investigating for the first time the effect of the association ethinylestradiol30μg-drospirenone 3mg (DRP/EE30μg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS).Methods25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30μg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention.ResultsThe combination between DRP/EE30μg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p < 0.05). Regarding hsCRP levels, there was no significant intragroup (PCOS6months – PCOSbasal) difference.ConclusionA 6-month course of metformin- DRP/EE30μg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445).

Evidence for visfatin as an independent predictor of endothelial dysfunction in polycystic ovary syndrome

Emerging evidence links adipocyte-secreted hormones, in particular adiponectin and visfatin, to cardiovascular pathology. Although adipocytokines dysregulation is common in polycystic ovary syndrome (PCOS) within the context of obesity and insulin resistance, their participation in the process of vascular injury remains elusive. This prospective, case-control study enrolled 102 young women (69 patients with PCOS and 33 eumenorrheic age-matched controls); serum adiponectin, resistin and visfatin, testosterone, SHBG, lipids, glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) were simultaneously measured in all participants. Body composition analysis was performed using dual X-ray absorptiometry. Endothelium impairment was assessed by carotid artery intimae-media thickness (CIMT) and brachial artery flow-mediated vasodilatation (FMD), respectively. In PCOS, both univariate and multivariate analyses evidenced that circulating visfatin was significantly related to free testosterone (P = 0·024) and brachial artery FMD (P = 0·008; P < 0·01 in multivariate analyses). By every visfatin tertile, a stepwise decrease in FMD was observed in all and PCOS only (P = 0·036), not confounded by age, body mass index, total body fat mass, testosterone, SHBG or HOMA-IR. Multiple regression analysis retained visfatin and free testosterone as independent predictors of FMD, explaining about 20% of FMD variability. Adiponectin correlated with CIMT and hs-CRP, but the association was driven by age, body mass and body fat. No relationship between resistin and endothelial markers was found. Visfatin may be a candidate to play a role in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors.

Nitric oxide and fibrinogen in polycystic ovary syndrome: Associations with insulin resistance and obesity

Objective Nitric oxide (NO) and fibrinogen levels, two markers of vascular disease, are associated with insulin resistance, a common trait in women with polycystic ovary syndrome (PCOS). Study design Case–control study including 31 women with PCOS and 21 age-matched women with regular, ovulatory cycles, normal androgen levels and idiopathic hirsutism (control group). Nitrite/nitrate concentration (index of endothelium-derived NO) and fibrinogen plasma levels were assessed and analysed in association with anthropometric, metabolic and hormonal variables. Results The groups were similar in terms of age, positive family history of diabetes and Ferriman–Gallwey hirsutism score. Nitrite/nitrate and fibrinogen levels were also similar in the two groups. In contrast, in PCOS patients, insulin levels and the homeostatic model assessment were negatively correlated with NO production ( r = −0.39, p = 0.03 and r = −0.41, p = 0.02, respectively). Age, BMI, waist circumference and waist-to-hip ratio were positively correlated with fibrinogen in both groups. Conclusion The present data indicate a negative, BMI-independent association between NO levels and insulin resistance in PCOS patients. Further studies are required to clarify the role of androgens on the pathogenesis of endothelial dysfunction in PCOS and investigate androgen action and/or the gene receptor modulating NO secretion.