scholarly journals Lipid-induced mononuclear cell cytokine secretion in the development of metabolic aberration and androgen excess in polycystic ovary syndrome

2020 ◽  
Vol 35 (5) ◽  
pp. 1168-1177
Author(s):  
F González ◽  
R V Considine ◽  
O A Abdelhadi ◽  
A J Acton
Keyword(s):  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
National Institutes Of Health ◽  
Reproductive Age ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Reproductive Age Women ◽  
Androgen Secretion

Abstract STUDY QUESTION What is the effect of saturated fat ingestion on mononuclear cell (MNC) TNFα, IL-6 and IL-1β secretion and circulating IL-6 levels in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Women with PCOS exhibit increases in MNC-derived TNFα, IL-6 and IL-1β secretion and circulating IL-6 following saturated fat ingestion even in the absence of obesity, and these increases are linked to metabolic aberration and androgen excess. WHAT IS KNOWN ALREADY Cytokine excess and metabolic aberration is often present in PCOS. STUDY DESIGN, SIZE, DURATION A cross-sectional design was used in this study of 38 reproductive-age women. PARTICIPANTS/MATERIALS, SETTING, METHODS Groups of 19 reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory controls (10 lean, 9 obese) participated in this study that was performed at a tertiary academic medical centre. TNFα, IL-6 and IL-1β secretion was measured from cultured MNC, and IL-6 was measured in plasma from blood sampling while fasting and 2, 3 and 5 h after saturated fat ingestion. Insulin sensitivity was determined using the Matsuda index following an oral glucose tolerance test. Androgen secretion was evaluated with blood sampling while fasting and 24, 48 and 72 h after an HCG injection. MAIN RESULTS AND THE ROLE OF CHANCE Lean and obese women with PCOS exhibited lipid-induced incremental AUC increases in MNC-derived TNFα (489–611%), IL-6 (333–398%) and IL-1β (560–695%) secretion and in plasma IL-6 levels (426–474%), in contrast with lean control subjects. In both PCOS groups, insulin sensitivity was lower (42–49%) and androgen secretion after HCG injection was greater (63–110%) compared with control subjects. The MNC-derived TNFα, IL-6 and IL-1β and circulating IL-6 responses were inversely associated with insulin sensitivity and directly associated with fasting lipids and androgen secretion after HCG injection. LIMITATIONS, REASONS FOR CAUTION The sample size of each of the four study groups was modest following group assignment of subjects by body mass. WIDER IMPLICATIONS OF THE FINDINGS This study showcases the unique pro-inflammatory contribution of circulating MNC in the development of metabolic aberration and androgen excess in PCOS. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grant R01 DK107605 to F.G. from the National Institutes of Health, the Indiana Clinical and Translational Sciences Institute Clinical Research Center which is funded in part by grant UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana University Center for Diabetes and Metabolic Diseases funded by grant P30 DK097512 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflicts of interest, financial or otherwise, are declared by the authors. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT01489319

scholarly journals Androgen Receptor Blocker Improves the Cardiometabolic Profile in a Rat Model of Polycystic Ovary Syndrome, but at What Cost?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A803-A804
Author(s):  
Jacob E Pruett ◽  
Steven Everman ◽  
Edgar David Torres Fernandez ◽  
Kacey Davenport ◽  
Damian G Romero ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Female Rats ◽  
Chow Diet ◽  
Model Assessment ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Glutamyl Transferase ◽  
Cardiometabolic Profile

Abstract Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is characterized by androgen excess and ovulatory dysfunction high prevalence of cardiovascular risk factors such as increased blood pressure (BP), insulin resistance (IR), and obesity. We have demonstrated previously that exposing prepubertal female rats to dihydrotestosterone (DHT) leads to increase in food intake (FI), body weight (BW), BP, and IR. We tested the hypothesis that administration of the AR blocker bicalutamide (BICA) would decrease BP, IR, and obesity in PCOS model. As there are previous reports of severe hepatotoxicity with the AR blocker flutamide, we also examined BICA effects in the liver. Methods: Four-week old female Sprague Dawley rats implanted with DHT pellets (7.5mg/90 days) or placebo (PBO) were randomized to standard chow diet with or without the AR blocker bicalutamide (BICA) at a dose of 250 mg/kg/day throughout the study (n=10/group). BW and FI were measured weekly. BP and heart rate (HR) were measured by radiotelemetry. Fasting plasma was collected for IR (Homeostatic model assessment for IR, HOMA-IR). At euthanasia, the liver was collected, as well as plasma for gamma glutamyl transferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) quantification. Results: PCOS rats had increased BW, FI, IR, and BP compared to PBO. BICA treatment had no impact on BW (285.3 ± 7.0 vs 270 ± 8.2 g, P=0.2) as well as FI and HR in PCOS. However, in PCOS, BICA decreased HOMA-IR (5.10 ± 0.40 vs 3.33 ± 0.31, P<0.05) and BP (115.4 ± 0.7 vs 105.3 ± 0.2 mmHg, P<0.01). Compared to PBO, PCOS+BICA rats had similar IR (3.83 ± 0.28 vs 3.33 ± 0.31, P=0.7) and BP (107.4 ± 0.8 vs 105.3 ± 0.2 mmHg, P=0.9). In addition, the liver weight to tibia length ratio was drastically increased by BICA in PCOS (222.9 ± 9.5 vs 360.4 ± 16.9 mg/mm, P<0.0001) as well as GGT (0.88 ± 0.88 vs 11.67 ± 0.58 U/L, P<0.0001), though it decreased AST (60.2 ± 6.9 vs 42.4 ± 1.9 U/L, P<0.05) and had no impact on ALT. Conclusion: In summary, in a model of PCOS, BICA treatment abolished IR and BP, independent of FI, BW and HR. Prompt treatment with an AR blocker can normalize increased IR and BP triggered by androgen excess in females. Further studies need to be done to fully understand the effect of BICA in the liver in PCOS. The beneficial effect of AR blockers as a therapeutic option to improve the cardiometabolic profile in PCOS may be hampered by its liver toxicity.

scholarly journals Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Bingjie Zhang ◽  
Jing Wang ◽  
Shanmei Shen ◽  
Jiayi Liu ◽  
Jie Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Glucose Intolerance ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Sensitivity Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Family History Of Diabetes

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

scholarly journals Polycystic Ovary Syndrome and Dietary Patterns in Iran: A Review Study

2019 ◽  
Author(s):  
Asieh Panjeshahin ◽  
Maryam Khosravi ◽  
Mahdieh Hosseinzadeh
Keyword(s):  
Food Intake ◽  
Polycystic Ovary Syndrome ◽  
Dietary Patterns ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Reproductive Age ◽  
Comprehensive Treatment ◽  
Dietary Habit ◽  
Ovary Syndrome ◽  
Total Calorie

Background: Polycystic Ovary Syndrome (PCOs) is one of the most common metabolic and endocrine abnormalities among women in reproductive age. In the case of not comprehensive treatment, PCOs can lead to hormonal, metabolic, and fertility disorders.  The exact cause of PCOs is still unclear. This disease seems to have a genetic background caused by the interference of several key genes with the environmental factors such as dietary habit and food intake, which play an important role in prevention and treatment of this syndrome. Methods: We searched Scopus, PubMed, SID, and Magiran data bases to find the studies conducted in Iran on dietary patterns, dietary intake, food intake, and PCOs published in English. Results: The findings showed that decrease of weight and fat intake from total calorie (especially saturated fat and cholesterol), increase of physical activity and intake of dietary fibers can improve this syndrome. Furthermore, DASH diet, increase of the protein/carbohydrate ratio in the diet, the low-calorie diets, or iso-caloric diets with a low glycemic index can also be useful in this regard. Discussion: In recent studies, the effects of some healthy diets were studied on PCOs women. A few of these studies were about finding appropriate dietary patterns for PCOs patients, but their number was limited. So, further studies are needed in this regard.

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.

scholarly journals Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

2009 ◽  
Vol 161 (5) ◽  
pp. 737-745 ◽  
Author(s):  
Flavia Tosi ◽  
Romolo Dorizzi ◽  
Roberto Castello ◽  
Claudio Maffeis ◽  
Giovanna Spiazzi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Body Fat ◽  
Polycystic Ovary ◽  
C Reactive Protein ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Reactive Protein ◽  
Hs Crp

ObjectiveIncreased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association.Design and methodsSerum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6±4.2 years, body mass index (BMI) 23.6±3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance.ResultsHs-CRP concentrations were higher in PCOS women (3.43±2.01 mg/l) than in HA subjects and healthy women (2.43±1.04, P<0.005; and 2.75±0.86 mg/l, P<0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable.ConclusionsPCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

scholarly journals Controversies in the diagnosis of polycystic ovary syndrome

2020 ◽  
Vol 14 ◽  
pp. 263349412091303
Author(s):  
Preetham Rao ◽  
Priya Bhide
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Reproductive Age ◽  
Polycystic Ovaries ◽  
Women Of Reproductive Age ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Ultrasound Features

Polycystic ovary syndrome is a common endocrinological condition which is found to be prevalent in 5–10% of women of reproductive age. Historically, a combination of anovulation and androgen excess was considered a hallmark in the diagnosis of polycystic ovary syndrome. Addition of ultrasound features of polycystic ovary syndrome has improved the detection of variation in the polycystic ovary syndrome phenotype. Despite the widespread use of consensus diagnostic criteria, there remain several unresolved controversies in the diagnosis of polycystic ovary syndrome. Difficulty arises in methods of assessment and types of androgens to be measured to detect biochemical hyperandrogenism, setting a cut-off value for the diagnosis of clinical hyperandrogenism, setting an ultrasound threshold of antral follicle count to diagnose polycystic ovaries and also diagnosing this condition in adolescence where there is no clear definition for ‘irregular cycles’. This article looks at various controversies in the diagnosis of polycystic ovary syndrome.

scholarly journals Oxidative Stress in Response to Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (11) ◽  
pp. 5360-5371 ◽  
Author(s):  
Frank González ◽  
Robert V Considine ◽  
Ola A Abdelhadi ◽  
Anthony J Acton
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Protein Content ◽  
Polycystic Ovary ◽  
Saturated Fat ◽  
Ros Generation ◽  
Ovary Syndrome ◽  
Control Subjects ◽  
Androgen Secretion

Abstract Context Oxidative stress and insulin resistance are often present in polycystic ovary syndrome (PCOS). Objective We determined the effect of saturated fat ingestion on leukocytic reactive oxygen species (ROS) generation, p47phox expression, and circulating thiobarbituric acid–reactive substances (TBARS) in women with PCOS. Design Cross-sectional study. Setting Academic medical center. Patients Twenty women of reproductive age with PCOS (10 lean, 10 with obesity) and 19 ovulatory control subjects (10 lean, 9 with obesity). Main Outcome Measures ROS generation and p47phox mRNA and protein content were quantified in leukocytes, and TBARS was measured in plasma from blood drawn while the subjects were fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood drawn while the subjects were fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. Results Regardless of weight class, women with PCOS exhibited lipid-induced increases in leukocytic ROS generation and p47phox mRNA and protein content as well as plasma TBARS compared with lean control subjects. Both PCOS groups exhibited lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. The ROS generation, p47phox, and TBARS responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion In PCOS, increases in ROS generation, p47phox gene expression, and circulating TBARS in response to saturated fat ingestion are independent of obesity. Circulating mononuclear cells and excess adipose tissue are separate and distinct contributors to oxidative stress in this disorder.

scholarly journals Heterogeneity of Endocrinologic and Metabolic Parameters in Reproductive Age Polycystic Ovary Syndrome (PCOS) Women Concerning the Severity of Hyperandrogenemia—A New Insight on Syndrome Pathogenesis

2020 ◽  
Vol 17 (24) ◽  
pp. 9291
Author(s):  
Katarzyna Ozegowska ◽  
Marcin Korman ◽  
Agnieszka Szmyt ◽  
Leszek Pawelczyk
Keyword(s):  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Dehydroepiandrosterone Sulfate ◽  
Reproductive Age ◽  
Metabolic Parameters ◽  
Ovary Syndrome ◽  
Group 3

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women’s clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. Results: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = −0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. Conclusions: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.

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