scholarly journals Identification of a Polycystic Ovary Syndrome Susceptibility Variant in Fibrillin-3 and Association with a Metabolic Phenotype

2007 ◽  
Vol 92 (11) ◽  
pp. 4191-4198 ◽  
Author(s):  
Margrit Urbanek ◽  
Susan Sam ◽  
Richard S. Legro ◽  
Andrea Dunaif
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Academic Medical Center ◽  
Susceptibility Locus ◽  
Metabolic Phenotype ◽  
Model Assessment ◽  
Metabolic Abnormalities ◽  
Ovary Syndrome ◽  
Increased Risk

Abstract Context: Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is also associated with metabolic abnormalities including insulin resistance and an increased risk for diabetes mellitus. We previously mapped a PCOS susceptibility locus to chromosome 19p13.2 near the dinucleotide repeat marker D19S884. Objective: Our objective is to localize the chromosome 19p13.2 PCOS susceptibility locus and determine its impact on metabolic features of PCOS. Design: Resequencing and family-based association testing were used to examine the effect of sequence variation within 100 kb of D19S884 on the reproductive and metabolic phenotypes of PCOS. Setting: The study was conducted in an academic medical center. Subjects: Genetic analyses were performed on DNA obtained from1723 individuals in 412 families with 412 index cases and 43 affected sisters of predominantly European origin (>94%). Genotype-phenotype associations were assessed in 601 women with PCOS and 168 brothers of affected women. Results: D19S884 allele 8 (A8) within intron 55 of the fibrillin-3 (FBN3) gene showed the strongest evidence for association with PCOS of 53 variants tested (Pcorrected = 0.0037). A8 was also associated with higher levels of fasting insulin and homeostasis model assessment for insulin resistance in women with PCOS and higher fasting levels of proinsulin and proinsulin/insulin ratio in brothers. Conclusions: These findings strongly suggest that A8 of D19S884 is the chromosome 19p13.2 PCOS susceptibility locus. The association of D19S884 with markers of insulin resistance and pancreatic β-cell dysfunction suggests that the same variant contributes to the reproductive and metabolic abnormalities of PCOS in affected women and their brothers.

scholarly journals Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome

2014 ◽  
Vol 171 (3) ◽  
pp. 301-309 ◽  
Author(s):  
Sarantis Livadas ◽  
Anastasios Kollias ◽  
Dimitrios Panidis ◽  
Evanthia Diamanti-Kandarakis
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Early Years ◽  
Model Assessment ◽  
Metabolic Abnormalities ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
The Impact

BackgroundPolycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging.ObjectiveTo evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging.DesignA cross-sectional study was carried out to evaluate the diverse impacts of aging on IR.SettingAn outpatient clinic was chosen for the study.ParticipantsA total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group.Main outcome and measuresThe impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated.ResultsIn PCOS, age (−0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R2=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: −0.266, −0.233, −0.192, P<0.001), which was neutralized in obese patients (r: −0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles.ConclusionsAging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years.

scholarly journals Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Confidence Interval ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Meta Analysis ◽  
Mean Difference ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Synbiotic Supplementation

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.

scholarly journals Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women

2021 ◽  
Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Normal Weight ◽  
Model Assessment ◽  
Metabolic Function ◽  
Ovary Syndrome ◽  
Intravenous Glucose

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.

scholarly journals Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Total Testosterone ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Ovary Syndrome ◽  
Significant Difference

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.

Polycystic ovary syndrome: a contemporary clinical approach

2021 ◽  
Vol 27 ◽  
Author(s):  
Jelica Bjekić-Macut ◽  
Tamara Vukašin ◽  
Zelija Velija-Ašimi ◽  
Azra Bureković ◽  
Marija Zdravković ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Cardiovascular Complications ◽  
Reproductive Period ◽  
Clinical Approach ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Central Type ◽  
Increased Risk

: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have central type of obesity, more prevalently displaying dyslipidemia, insulin resistance and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium glucose contransporter-2 (SGLT2) inhibitors. Addition of an insulin sensitizer to the standard infertility therapy such as CC improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.

Obesity, hormonal and metabolic abnormalities in adolescent girls with polycystic ovary syndrome

2013 ◽  
Vol 154 (31) ◽  
pp. 1226-1234
Author(s):  
László Ságodi ◽  
Béla Lombay ◽  
Ildikó Vámosi ◽  
László Barkai
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Polycystic Ovary Syndrome ◽  
Adolescent Girls ◽  
Polycystic Ovary ◽  
Metabolic Abnormalities ◽  
Ovary Syndrome

Introduction: Polycystic ovary syndrome is associated with metabolic abnormalities, such as dyslipidemia, obesity, glucose intolerance, which are also components of the metabolic syndrome. Central obesity and insulin resistance appear to play an important role in the pathogenesis of polycystic ovary syndrome, perhaps via subsequent steroidogenic dysregulation. Aim: The aim of the authors was to assess metabolic and hormonal abnormalities in adolescent girls with polycystic ovary syndrome. Method: The study included 52 adolescents diagnosed with polycystic ovary syndrome based on the Rotterdam criteria. Anthropometric, hormonal and metabolic parameters were evaluated among all subjects. 20 healthy, age-matched, non-obese, regularly menstruating girls were used as controls. Of the 52 patients, 15 patients were born with low-birth-weight and 37 patients were born with normal birth weight. Oral glucose tolerance test was performed in all patients and controls. The age of patients was 16.8±3.1 years, and the age of controls was 16.95±2.1 years. Results: Among patients with polycystic ovary syndrome the prevalence of overweight and obesity was 35% (n = 18), while impaired fasting glucose occurred in one patient, impaired glucose tolerance in 8 patients, insulin resistance in 25 patients and metabolic syndrome in 12 patients. Serum triglyceride levels in patients and controls were 1.4±0.8 and 0.9±0.3 mmol/l, respectively (p<0.05), while fasting blood glucose, total cholesterol, HDL and LDL cholesterol were not different in the two groups. Metabolic abnormalities and obesity were more severe and more frequent in patients with low-birth-weight compared to those born with normal weight. There was a negative correlation between birth weight and body mass index SDS values and a positive correlation between fasting insulin levels and body mass index SDS (r = 0.37) in patients born with low-birth-weight. Conclusions: Abnormal glucose metabolism is frequently present in adolescents with polycystic ovary syndrome. It is possible that early diagnosis of polycystic ovary syndrome in adolescences may prevent some of the long-term complications associated with this syndrome. Orv. Hetil., 2013, 154, 1226–1234.

scholarly journals Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism

2017 ◽  
Vol 39 (05) ◽  
pp. 224-228 ◽  
Author(s):  
Cristina Benetti-Pinto ◽  
Vanessa Piccolo ◽  
Daniela Yela ◽  
Heraldo Garmes
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Thyroid Stimulating Hormone ◽  
Metabolic Parameters ◽  
Overt Hypothyroidism ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
Stimulating Hormone

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.

scholarly journals Developmental origin of polycystic ovary syndrome - a hypothesis

2002 ◽  
Vol 174 (1) ◽  
pp. 1-5 ◽  
Author(s):  
DH Abbott ◽  
DA Dumesic ◽  
S Franks
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Regulatory Region ◽  
Later Life ◽  
Ovary Syndrome ◽  
Increased Risk ◽  
Genetically Determined ◽  
Lh Secretion

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

scholarly journals Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

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
Keyword(s):  
Insulin Resistance ◽  
Oral Contraceptive ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Total Testosterone ◽  
Model Assessment ◽  
Cycle Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Improve Insulin Resistance

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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