scholarly journals Anti-Müllerian Hormone Accelerates Pathological Process of Insulin Resistance in Polycystic Ovary Syndrome Patients

2021 ◽  
Vol 53 (08) ◽  
pp. 504-511
Author(s):  
Xiang-Juan Li ◽  
Hui Wang ◽  
Dan-Yang Lu ◽  
Tian-Tian Yu ◽  
Kamran Ullah ◽  
...  

AbstractInsulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic β-cells in obese PCOS women.

Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.


2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.


2018 ◽  
Vol 127 (09) ◽  
pp. 571-577
Author(s):  
Xinwei Chen ◽  
Lijing Huo ◽  
Luping Ren ◽  
Yali Li ◽  
Yanmei Sun ◽  
...  

Abstract Purpose Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients. Methods In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well. Results Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman’s correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels. Conclusion PCOS is associated with elevated levels of periostin.


2019 ◽  
Vol 31 (2) ◽  
pp. 315 ◽  
Author(s):  
Asma Neisy ◽  
Fatemeh Zal ◽  
Atefeh Seghatoleslam ◽  
Sanaz Alaee

Insulin resistance (IR) and infertility are two major complications of polycystic ovary syndrome (PCOS), which are the results of changes in certain parts of the reproductive and metabolic systems. We aimed to observe the effect of quercetin on dehydroepiandrosterone (DHEA)-induced PCOS and insulin resistance in rats. All animals were divided into five groups and DHEA was used to induce PCOS. Bodyweight and ovarian morphology of all groups were observed. Fasting blood glucose and insulin levels were analysed. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used for IR level determination. The expression of oestrogen receptor α (ERα) and glucose transporter 4 (GLUT4) genes in the uterus was examined by real-time polymerase chain reaction. Liver hexokinase (HK) and glucokinase (GK) activity was determined using spectrophotometry. Quercetin significantly improved the IR state in PCOS rats. PCOS resulted in a decrease in liver GK and an increase in liver HK specific activity, whereas quercetin increased both liver HK and GK activity. Our data also showed a significant reduction in uterine ERα and GLUT4 expression in the PCOS group, which was increased by quercetin. A remarkable effect of quercetin was the intensive reduction of PCOS-IR and significant induction of uterine GLUT4 and ERα gene expression; it could thus be a possible effective treatment for PCOS and its complications, IR and infertility.


2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tommy Kyaw Tun ◽  
Anne McGowan ◽  
Niamh Phelan ◽  
Neuman Correia ◽  
Gerard Boran ◽  
...  

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.


Author(s):  
Cristina Benetti-Pinto ◽  
Vanessa Piccolo ◽  
Daniela Yela ◽  
Heraldo Garmes

Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 – 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yuanyuan Guan ◽  
Dongjun Wang ◽  
Huaien Bu ◽  
Tieniu Zhao ◽  
Hongwu Wang

Objective. Metformin is an important component of PCOS treatment. At present, the effect of metformin in overweight women with PCOS has not been evaluated. Therefore, we conducted a systematic review to assess the effects of metformin in overweight women with PCOS and to analyze the effects of metformin in overweight women with PCOS. Methods. We searched the PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases for studies published before March 2020. Randomized controlled trials were identified to study the effects of metformin in overweight women with PCOS. Data from studies including body mass index (BMI), waist circumference (WC), follicle-stimulating hormone (FSH), homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), fasting blood glucose (FBG), fasting insulin, testosterone, and androstenedione were pooled. Qualified trials were selected, and methodological quality was strictly assessed. Two reviewers chose the studies independently of each other. Results. Twelve trials were included. The intervention group and the control group had significant differences in the changes in body mass index (BMI) (WMD = −1.25, 95% CI (−1.60, −0.91), p<0.00001) and waist circumference (WC) (WMD = −1.41, 95% CI (−2.46, −0.37), p=0.008) after metformin. The comprehensive results show that, in all studies, overweight women with polycystic ovary syndrome treated with metformin had significantly improved endocrine and metabolic indicators, including testosterone, follicle-stimulating hormone, luteinizing hormone, and low-density lipoprotein cholesterol. However, metformin did not regulate the secretion indexes of fasting insulin, homeostasis model assessment of insulin resistance, sex hormone-binding globulin, high-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting blood glucose, and androstenedione. Conclusions. Compared with control interventions, metformin appears to be an effective intervention for overweight women with PCOS.


2015 ◽  
Vol 61 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Margareth Chiharu Iwata ◽  
Livia Porquere ◽  
Isabel C. Espósito Sorpreso ◽  
Edmund C. Baracat ◽  
José Maria Soares Júnior

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.


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