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Nandi A, Singh K, Sharma K. Advancement in early diagnosis of polycystic ovary syndrome: biomarker-driven innovative diagnostic sensor. Mikrochim Acta 2025; 192:331. [PMID: 40310524 DOI: 10.1007/s00604-025-07187-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous multifactorial endocrine disorder that affects one in five women around the globe. The pathology suggests a strong polygenic and epigenetic correlation, along with hormonal and metabolic dysfunction, but the exact etiology is still a mystery. The current diagnosis is mostly based on Rotterdam criteria, which resulted in a delayed diagnosis in most of the cases, leading to unbearable lifestyle complications and infertility. PCOS is not new; thus, constant efforts are made in the field of biomarker discovery and advanced diagnostic techniques. A plethora of research has enabled the identification of promising PCOS diagnostic biomarkers across hormonal, metabolic, genetic, and epigenetic domains. Not only biomarker identification, but the utilization of biosensing platforms also renders effective point-of-care diagnostic devices. Artificial intelligence also shows its power in modifying existing image-based analysis, even developing symptom-based prediction systems for the early diagnosis of this multifaceted disorder. This approach could affect the future management and treatment direction of PCOS, decreasing its severity and improving the reproductive life of women. The rationale of the current review is to identify the advancements in understanding the pathophysiology through biomarker discovery and the implementation of modern analytical techniques for the early diagnosis of PCOS.
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Affiliation(s)
- Aniket Nandi
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, G.T Road, Ghal Kalan, Moga, Punjab, 142001, India
| | - Kamal Singh
- Bond Life Sciences Center, and Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA
| | - Kalicharan Sharma
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, G.T Road, Ghal Kalan, Moga, Punjab, 142001, India.
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Wongwananuruk T, Prasongvej P, Chantrapanichkul P, Indhavivadhana S, Tanmahasamut P, Rattanachaiyanont M, Techatraisak K, Angsuwathana S. Measures of Serum Markers HbA1c, HOMA-IR, HOMA-β, QUICKI and G/I Ratio as Predictors of Abnormal Glucose Tolerance Among Thai Women with Polycystic Ovary Syndrome. J Clin Med 2025; 14:1452. [PMID: 40094911 PMCID: PMC11900011 DOI: 10.3390/jcm14051452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/24/2025] [Accepted: 02/17/2025] [Indexed: 03/19/2025] Open
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age. It is associated with glucose intolerance, insulin resistance and diabetes mellitus. The oral glucose tolerance test (OGTT) is commonly employed to detect glucose intolerance, but it can be inconvenient and time-consuming. We aimed to evaluate the precision of haemoglobin A1c (HbA1c) and other serum markers in predicting abnormal glucose tolerance (AGT). Methods: This diagnostic study involved 121 PCOS women who attended the Gynaecologic Endocrinology Unit at Siriraj Hospital. Patients underwent assessments for weight, height, waist circumference, modified Ferriman-Gallwey score and acanthosis nigricans. Blood samples were collected to measure fasting glucose and insulin levels after a 75-gram oral OGTT, fasting insulin level, HbA1c, lipid profile, androgen profile and complete blood count. Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI) and fasting glucose-to-insulin ratio (G/I ratio) were calculated. The sensitivity, specificity and accuracy of these serum markers were compared. Results: The prevalence of AGT was 24.8%. The area under the receiver operating characteristic curve for HbA1c in detecting AGT was 0.656, while HOMA-IR, HOMA-β, QUICKI and the G/I ratio had values of 0.817, 0.737, 0.817 and 0.77, respectively. The G/I ratio cut-off point of 6% demonstrated a sensitivity of 73.3%, specificity of 74.7%, positive predictive value of 48.9%, negative predictive value of 89.5% and accuracy of 74.4%. Conclusions: The G/I ratio is the most accurate compared to other serum markers in detecting AGT among Thai women with PCOS.
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Affiliation(s)
- Thanyarat Wongwananuruk
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Pichita Prasongvej
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand
| | - Panicha Chantrapanichkul
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Suchada Indhavivadhana
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Prasong Tanmahasamut
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Manee Rattanachaiyanont
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Kitirat Techatraisak
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Surasak Angsuwathana
- Gynaecologic Endocrinology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
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Belsti Y, Enticott J, Azumah R, Tay CT, Moran L, Ma RCW, Joham AE, Laven J, Teede H, Mousa A. Diagnostic accuracy of oral glucose tolerance tests, fasting plasma glucose and haemoglobin A1c for type 2 diabetes in women with polycystic ovary syndrome: A systematic review and meta-analysis. Diabetes Metab Syndr 2024; 18:102970. [PMID: 38442646 DOI: 10.1016/j.dsx.2024.102970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 02/15/2024] [Accepted: 02/19/2024] [Indexed: 03/07/2024]
Abstract
AIMS To inform international guidelines, a systematic review and meta-analysis was conducted to assess the performance of diagnostic methods for type 2 diabetes in women with polycystic ovary syndrome (PCOS). METHODS An updated systematic search was conducted on five databases from 2017 until October 2023 and combined with prior searches (from inception). Meta-analyses of diagnostic accuracy tests were conducted. RESULTS Nine studies comprising 2628 women with PCOS were included. Against the oral glucose tolerance test, a haemoglobin A1C (HbA1c) ≥ 6.5% had a pooled sensitivity of 50.00% (95% confidence interval (CI): 35.53-64.47), specificity of 99.86% (95%CI: 99.49-99.98), and positive and negative predictive values of 92.59% (95%CI: 75.27-98.09) and 98.27% (95%CI: 97.73-98.68), respectively, with an accuracy of 98.17% (95%CI: 97.34-98.79). Fasting plasma glucose values ≥ 7.0 mmol/L had a pooled sensitivity of 58.14% (95%CI: 42.13-72.99), specificity of 92.59% (95%CI: 75.35-98.08), positive and negative predictive values of 92.59% (95%CI: 75.35-98.08) and 99.09% (95%CI: 98.71-99.36), respectively, and an accuracy of 99.00% (95%CI: 98.46-99.39) against the oral glucose tolerance test. CONCLUSIONS To our knowledge, this is the first systematic review assessing the performance of diagnostic methods for type 2 diabetes in women with PCOS. We demonstrate that using a cut-off for HbA1c of ≥6.5% in this population may result in misdiagnosis of half of the women with type 2 diabetes. Our results directly informed the recommendations of the 2023 International PCOS Guideline, suggesting that the oral glucose tolerance test is the optimal method for screening and diagnosing type 2 diabetes in women with PCOS and is superior to fasting plasma glucose and HbA1c.
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Affiliation(s)
- Yitayeh Belsti
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Joanne Enticott
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Rafiatu Azumah
- Robinson Research Institute, The University of Adelaide AHMS Building, North Terrace, Adelaide, South Australia, 5005, Australia
| | - Chau Thien Tay
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Lisa Moran
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Ronald C W Ma
- Dept of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, China
| | - Anju E Joham
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Diabetes and Endocrine Units, Monash Health, Melbourne, Victoria, 3168, Australia
| | - Joop Laven
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Helena Teede
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Diabetes and Endocrine Units, Monash Health, Melbourne, Victoria, 3168, Australia
| | - Aya Mousa
- Monash Centre for Health Research and Implementation (MCHRI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
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Amisi CA. Markers of insulin resistance in Polycystic ovary syndrome women: An update. World J Diabetes 2022; 13:129-149. [PMID: 35432749 PMCID: PMC8984569 DOI: 10.4239/wjd.v13.i3.129] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 09/14/2021] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.
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Affiliation(s)
- Chantal Anifa Amisi
- Endocrinology and Diabetes Unit, Department of Medicine, Universita Campus Bio-medico di Rome, Rome 00128, Italy
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Prabhu YD, Borthakur A, A G S, Vellingiri B, Valsala Gopalakrishnan A. Increased pro-inflammatory cytokines in ovary and effect of γ-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model. J Reprod Immunol 2021; 146:103345. [PMID: 34116484 DOI: 10.1016/j.jri.2021.103345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/29/2021] [Accepted: 06/03/2021] [Indexed: 11/25/2022]
Abstract
Polycystic Ovary Syndrome (PCOS), a major endocrine disorder, affects the reproductive function of a woman, along with an association with metabolic conditions like insulin resistance and inflammation. The inflammatory nature of PCOS is much debated over, owing to numerous cases of elevation in cytokine levels. Studies have shown the beneficiary effect of Gamma-Linolenic acid (GLA) in reducing inflammation related to many conditions such as atopic dermatitis, rheumatoid arthritis, arterial disease, obesity, and even PCOS. The study aims at assessing the expression of inflammatory cytokines in the ovary and Peri-ovarian adipose tissue (POAT) of the Dehydroepiandrosterone (DHEA) induced PCOS rat model. Further, this study also evaluates the effect of γ-linolenic Acid (GLA) on these cytokines in POAT. Female Wistar rats were subcutaneously injected with 60 mg/kg DHEA daily for 28 days. These PCOS-induced rats were then orally administered with 50 mg/kg GLA for 14 days. The gene expression of cytokines was assessed by Real Time-PCR. The study showed an increase in the expression of cytokines in the ovary and POAT of the DHEA group. This suggests the role of ovarian adipose in adding to the pro-inflammatory state of PCOS. Moreover, the administration of GLA to the PCOS-induced rats resulted in a reduction of cytokine expression from the POAT, indicating that the compound was successful in reducing the associated inflammation. The study throws light on the possibility of using GLA as a supplementary or naturalistic alternative in ameliorating ovarian adipose-associated inflammation that accompanies PCOS.
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Affiliation(s)
- Yogamaya D Prabhu
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Atreyee Borthakur
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Subeka A G
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India
| | - Balachandar Vellingiri
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India.
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Pani A, Gironi I, Di Vieste G, Mion E, Bertuzzi F, Pintaudi B. From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management. Int J Endocrinol 2020; 2020:6276187. [PMID: 32587614 PMCID: PMC7298266 DOI: 10.1155/2020/6276187] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/13/2020] [Indexed: 12/20/2022] Open
Abstract
AIMS Despite the very clear association between polycystic ovary syndrome (PCOS) and dysglycemia, few studies have explored the continuum of glycemic alterations leading from minor glucose abnormalities to overt diabetes. The purpose of this review is to trace the natural history of glycemic alteration in women with PCOS. METHODS We performed a literature review without time limit until August 2019. Inclusion criteria were studies addressing the association between impaired glucose tolerance or impaired fasting glucose or type 2 diabetes (T2D) and PCOS with at least an English abstract. The exclusion criteria were no PCOS or impaired glucose tolerance or impaired fasting glucose or T2D as outcome. The outcomes of interest were the onset of impaired glucose tolerance, impaired fasting glucose, T2D, and the progression from impaired glucose tolerance or impaired fasting glucose to T2D. RESULTS Healthy diet and physical activity are the first-line therapy for PCOS. Treatment with metformin was associated with significant lower 2-hour postload glucose levels and with reduction in fasting glucose when compared to placebo. Thiazolidinediones were more effective in reducing fasting glucose levels compared to placebo. Metformin and pioglitazone treatments showed similar effects on fasting glucose levels. The sodium-glucose cotransporter-2 inhibitor empagliflozin did not show differences in metabolic parameters when compared to metformin. The combination therapy with metformin plus the glucagon-like peptide-1 receptor agonist liraglutide was associated with significant improvements in basal and postload glucose levels compared with only liraglutide. Likewise, a combination therapy with the dipeptidyl peptidase-4 inhibitor saxagliptin and metformin demonstrated superiority versus metformin in fasting glucose and oral glucose tolerance test normalization. Myo-inositol supplementation was associated with lower insulin levels, glucose levels, and insulin resistance when compared with placebo, metformin, or estrogen treatments. CONCLUSIONS The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women.
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Affiliation(s)
- Arianna Pani
- Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, Milan, Italy
| | | | | | - Elena Mion
- Diabetes Unit, Niguarda Cà Granda Hospital, Milan, Italy
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Bao L, Syed R, Aloahd MS. Analysis of VEGF gene polymorphisms and serum VEGF protein levels contribution in polycystic ovary syndrome of patients. Mol Biol Rep 2019; 46:5821-5829. [PMID: 31385237 DOI: 10.1007/s11033-019-05015-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/30/2019] [Indexed: 12/15/2022]
Abstract
Vascular endothelial growth factor (VEGF) is a well-known factor in reproductive function and contributes to the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in VEGFA gene were suggested to contribute alterations in VEGF secretion and PCOS. This study evaluated the association of VEGFA SNPs with altered VEGF secretion level and PCOS among ethnically-matched control women. This prospective case-control study was conducted from 2016 to 2018 and comprised of 55 women with PCOS and 52 control subjects. ELISA was used to measure VEGF levels; and various other related bio chemicals whereas the genotyping of VEGFA variants was performed through the analysis of nine SNPs of VEGF. PRL, E2, PRGE testosterone and glucose level were found to be insignificantly different. The levels of FSH, LH, LH/FSH, TT, insulin, SHBG and HOMA-IR were significantly higher in the study group. Among the nine tested variants of VEGF SNPs, two SNPs rs3025020 and rs833061, consisted of TT (Recessive and Dominant homozygous, respectively) which were marginally higher in test. The SNP rs1570360 had significantly higher GG allele (32.73%) which was recessive homozygous. There was no significant difference observed in genotype frequencies related to higher value of VEGF. The genotype frequencies for the studied SNPs were in alignment with Hardy-Weinberg equilibrium (HWE). The mean serum VEGF levels got significantly increased in PCOS group. No significant association was found between VEGF genotypes and its serum levels. VEGF levels in rs699947 (AA-major homozygous), rs3025039 (CC-major homozygous) and rs833061 (TT & CC-major & minor homozygous) genotypes were significantly higher in PCOS. The study results evidently proved that the allelic variants in genes may be a factor for PCOS and VEGF serum levels with respect to few SNP variants only. These findings indicated that VEGF may be involved in PCOS status and confirmed the previous association between genetic variants in VEGF, serum level of VEGF protein and PCOS.
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Affiliation(s)
- Lei Bao
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.,Shanghai Municipal Key Clinical Specialty, Shanghai, China
| | - Rabbani Syed
- Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia
| | - Mustafa Sawsan Aloahd
- College of Life Science, Maulana Azad College of Arts and Science, Aurangabad, India.
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Ortiz-Flores AE, Luque-Ramírez M, Fernández-Durán E, Alvarez-Blasco F, Escobar-Morreale HF. Diagnosis of disorders of glucose tolerance in women with polycystic ovary syndrome (PCOS) at a tertiary care center: fasting plasma glucose or oral glucose tolerance test? Metabolism 2019; 93:86-92. [PMID: 30710572 DOI: 10.1016/j.metabol.2019.01.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/22/2019] [Accepted: 01/26/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND The risk of developing prediabetes and type 2 diabetes (dysglycemia) may be increased in women with PCOS. Whether an oral glucose tolerance test (OGTT) should be performed routinely in all PCOS women at presentation or should be recommended only to a selected subset of patients is still controversial. BASIC PROCEDURES At a tertiary care center, we conducted a retrospective, observational study including 400 women with PCOS submitted to an OGTT. Our primary objective was to assess the diagnostic agreement between two algorithms commonly used for the screening of dysglycemia in these women: i) relying only on fasting plasma glucose (FPG) or ii) considering both fasting and/or 120-min plasma glucose concentrations during an OGTT. We conducted the analysis considering all patients as a whole, and also after stratifying them by body weight, androgen concentrations and age. MAIN FINDINGS The OGTT detected dysglycemia in 24.5% of patients, whereas only 14.3% women would have been diagnosed using FPG levels alone. The latter missed as many as 40% of women with dysglycemia in our series, including all cases of diabetes. Diagnostic agreement between both algorithms was only 0.55 (κ = 0.103; 95% CI: 0.05-0.16). Areas under the receiver operating characteristic curve for dysglycemia were 0.86 (95%CI: 0.81-0.91) for FPG and 0.91 (95%CI = 0.87-0.95) for 120-min plasma glucose during the OGTT. FPG was not accurate in predicting dysglycemia in women with PCOS regardless of the presence of insulin resistance, weight excess, hyperandrogenemia and age. PRINCIPAL CONCLUSIONS Relying on FPG alone is not adequate for the screening of disorders of glucose tolerance in women with PCOS; such diagnosis should rely on the results of an OGTT regardless of age, weight and/or androgen concentrations.
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Affiliation(s)
- Andrés E Ortiz-Flores
- Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, 28034, Spain
| | - Manuel Luque-Ramírez
- Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, 28034, Spain
| | - Elena Fernández-Durán
- Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, 28034, Spain
| | - Francisco Alvarez-Blasco
- Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, 28034, Spain
| | - Héctor F Escobar-Morreale
- Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, 28034, Spain.
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Andersen M, Glintborg D. Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT? Eur J Endocrinol 2018; 179:D1-D14. [PMID: 29921567 DOI: 10.1530/eje-18-0237] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 06/18/2018] [Indexed: 12/15/2022]
Abstract
Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.
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Affiliation(s)
- Marianne Andersen
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - Dorte Glintborg
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
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Lazaridou S, Dinas K, Tziomalos K. Prevalence, pathogenesis and management of prediabetes and type 2 diabetes mellitus in patients with polycystic ovary syndrome. Hormones (Athens) 2017; 16:373-380. [PMID: 29518757 DOI: 10.14310/horm.2002.1757] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 12/18/2017] [Indexed: 11/20/2022]
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. PCOS is not only the leading cause of anovulatory infertility but is also associated with an array of metabolic disorders, among which impaired glucose metabolism has been a topic of intense research. The aim of the present narrative review is to summarize the findings of the studies that have evaluated the prevalence and incidence of prediabetes and type 2 diabetes mellitus (T2DM) in patients with PCOS, to analyze the factors underpinning the association between T2DM and PCOS and to discuss the current strategies for screening and management of impaired glucose metabolism in this population. Both prediabetes and T2DM are highly prevalent in patients with PCOS. Accordingly, regular screening is recommended in this population for the early identification of impaired glucose metabolism, particularly in overweight or obese patients and in those with a family history of T2DM. Prevention of T2DM in patients with prediabetes is primarily based on lifestyle changes, while metformin might be considered in selected cases. The treatment of T2DM is similar in patients with and without PCOS but appropriate contraceptive measures should be implemented in patients receiving treatments other than insulin, metformin or glyburide.
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Affiliation(s)
- Sofia Lazaridou
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 1 Stilponos Kyriakidi Str., 54636, Thessaloniki, Greece
| | - Konstantinos Dinas
- Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 1 Stilponos Kyriakidi Str., 54636, Thessaloniki, Greece.
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11
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Rezaee M, Asadi N, Pouralborz Y, Ghodrat M, Habibi S. A Review on Glycosylated Hemoglobin in Polycystic Ovary Syndrome. J Pediatr Adolesc Gynecol 2016; 29:562-566. [PMID: 27593259 DOI: 10.1016/j.jpag.2016.07.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 07/19/2016] [Indexed: 12/17/2022]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders among women of reproductive age, with a variety of complications and consequences mostly due to hyperandrogenism and insulin resistance (IR). PCOS patients with IR are at risk for metabolic syndrome and diabetes mellitus (DM) along with its complications such as cardiovascular events. There are several methods for screening IR in patients with PCOS to predict DM and other complications. Fasting plasma glucose test, oral glucose tolerance test, and insulin and glycosylated hemoglobin (HbA1c) levels are some available screening tools for IR. The American Diabetes Association recommended HbA1c to screen for DM because HbA1c is not affected by day-to-day plasma glucose levels and reflects the plasma glucose status during 2-3 months before measurement. Some studies have evaluated the role of HbA1c as a screening method to predict DM in PCOS patients, however, there are still controversies in this matter. Also some studies reported that HbA1c has a correlation with complications of PCOS such as metabolic syndrome and cardiovascular events. We found that HbA1c could be a suitable screening test for IR in PCOS patients but more studies are recommended, omitting confounding factors that could affect IR in patients with PCOS, such as antihyperglycemic agents like metformin, or lifestyle modification, which can be effective in reducing IR in patients with PCOS.
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Affiliation(s)
- Mohsen Rezaee
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran
| | - Nasrin Asadi
- Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yasna Pouralborz
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran.
| | - Mahshid Ghodrat
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran
| | - Shaghayegh Habibi
- Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran
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12
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Almawi WY, Gammoh E, Malalla ZH, Al-Madhi SA. Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome. PLoS One 2016; 11:e0165636. [PMID: 27846231 PMCID: PMC5112863 DOI: 10.1371/journal.pone.0165636] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 10/14/2016] [Indexed: 02/07/2023] Open
Abstract
Background Vascular endothelial growth factor (VEGF) contributes to the pathogenesis of polycystic ovary syndrome (PCOS), and genetic variations in VEGFA gene were suggested to contribute to VEGF secretion and PCOS. Aim To evaluate the association of altered VEGF levels, stemming from the presence of specific VEGFA variants, with altered risk of PCOS. Subjects and Methods Retrospective case-control study, performed between 2012–2015. Study subjects comprised 382 women with PCOS, and 393 control subjects. ELISA measured VEGF levels; genotyping of VEGFA variants was done by allelic exclusion. Results Among the 12 tested VEGFA SNPs, minor allele frequency of only rs3025020 was significantly higher in PCOS cases than control women. Increased and reduced PCOS risk was seen with rs3025020 and rs2010963 genotypes, respectively. Increases and reduction in VEGF levels were associated with rs3025020 and rs2010963, respectively. Increased fasting insulin and HOMA-IR, and bioactive testosterone were linked with rs3025020, while carriage of rs2010963 was linked with reduction in fasting insulin, and free and bioactive testosterone. Of the 12 VEGFA variants, 9 were in LD, thus allowing construction of 9-locus haplotypes. Increased frequency of CAACAGCGA haplotype was seen in PCOS cases, after controlling for BMI, free and bioactive testosterone, SHBG, free insulin and HOMA-IR. Conclusion This study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into the pathogenesis of PCOS. This supports a role for VEGF as PCOS candidate locus.
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Affiliation(s)
- Wassim Y Almawi
- Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain
- * E-mail:
| | - Emily Gammoh
- Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain
| | - Zainab H. Malalla
- Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain
| | - Safa A. Al-Madhi
- Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain
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13
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Gourgari E, Spanakis E, Dobs AS. Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome. Int J Womens Health 2016; 8:381-7. [PMID: 27570464 PMCID: PMC4986967 DOI: 10.2147/ijwh.s104825] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have.
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Affiliation(s)
- Evgenia Gourgari
- Division of Pediatric Endocrinology, Georgetown University School of Medicine, Washington, DC
| | - Elias Spanakis
- Division of Endocrinology, University of Maryland School of Medicine
| | - Adrian Sandra Dobs
- Department of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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14
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Morris S, Grover S, Sabin MA. What does a diagnostic label of 'polycystic ovary syndrome' really mean in adolescence? A review of current practice recommendations. Clin Obes 2016; 6:1-18. [PMID: 26568133 DOI: 10.1111/cob.12123] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 09/21/2015] [Accepted: 10/01/2015] [Indexed: 12/20/2022]
Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long-term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label 'PCOS' is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome.
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Affiliation(s)
- S Morris
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - S Grover
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Centre for Hormone Research, Murdoch Childrens Research Institute and The Royal Children's Hospital, Melbourne, Victoria, Australia
| | - M A Sabin
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Centre for Hormone Research, Murdoch Childrens Research Institute and The Royal Children's Hospital, Melbourne, Victoria, Australia
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15
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Mayer SB, Evans WS, Nestler JE. Polycystic ovary syndrome and insulin: our understanding in the past, present and future. ACTA ACUST UNITED AC 2015; 11:137-49. [PMID: 25776288 DOI: 10.2217/whe.14.73] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and plays a critical pathophysiologic role in both the metabolic and reproductive complications of PCOS. This review focuses on the contribution of insulin resistance to anovulation in PCOS and to the high risk for Type 2 diabetes, metabolic syndrome and early cardiovasular disease. Key points for clinicians emphasized by this review are the following: PCOS is a clinical diagnosis and alternative diagnoses must be excluded; PCOS carries an inherent risk of insulin resistance and, hence, metabolic consequences for which women with PCOS should be screened regardless of BMI or degree of obesity; and PCOS is associated with infertility and this should be discussed early on in care of women diagnosed with PCOS, recognizing that there are several possible strategies to address infertility in women with PCOS, each with its own risks and benefits.
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Affiliation(s)
- Stéphanie B Mayer
- Division of Endocrinology & Metabolism, Virginia Commonwealth University, Richmond, VA, USA
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16
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Greenwood EA, Noel MW, Kao CN, Shinkai K, Pasch LA, Cedars MI, Huddleston HG. Vigorous exercise is associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure. Fertil Steril 2015; 105:486-93. [PMID: 26551442 DOI: 10.1016/j.fertnstert.2015.10.020] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 09/17/2015] [Accepted: 10/14/2015] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. DESIGN Cross-sectional study. SETTING Tertiary academic institution. PATIENT(S) Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013. INTERVENTION(S) International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. MAIN OUTCOME MEASURE(S) Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). RESULT(S) The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99). CONCLUSION(S) Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity.
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Affiliation(s)
- Eleni A Greenwood
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California.
| | - Martha W Noel
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California
| | - Chia-Ning Kao
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California
| | - Kanade Shinkai
- Department of Dermatology, University of California at San Francisco, San Francisco, California
| | - Lauri A Pasch
- Department of Psychiatry, University of California at San Francisco, San Francisco, California
| | - Marcelle I Cedars
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California
| | - Heather G Huddleston
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California
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17
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Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health 2015; 7:745-63. [PMID: 26261426 PMCID: PMC4527566 DOI: 10.2147/ijwh.s70314] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up.
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Affiliation(s)
- Stefano Palomba
- Unit of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova-Scientific Institute of Treatment and Care (IRCCS), Reggio Emilia, Modena, Italy
| | - Susanna Santagni
- Unit of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova-Scientific Institute of Treatment and Care (IRCCS), Reggio Emilia, Modena, Italy
| | - Angela Falbo
- Unit of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova-Scientific Institute of Treatment and Care (IRCCS), Reggio Emilia, Modena, Italy
| | - Giovanni Battista La Sala
- Unit of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova-Scientific Institute of Treatment and Care (IRCCS), Reggio Emilia, Modena, Italy ; Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy
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18
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Kelley CE, Brown AJ, Setji TL. Screening for glucose intolerance in polycystic ovary syndrome: hemoglobin A1C, fasting blood glucose or oral glucose tolerance test? Expert Rev Endocrinol Metab 2014; 9:671-683. [PMID: 30736203 DOI: 10.1586/17446651.2014.941814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a chronic condition with many reproductive, metabolic and psychological manifestations. Insulin resistance puts women with PCOS at an increased risk for developing impaired glucose tolerance (IGT) and diabetes (T2D). An oral glucose tolerance test is the preferred IGT/T2D screening test, since it is most sensitive for detecting early glucose abnormalities. The goals in detecting IGT in these women are to avoid progression to T2D, modify cardiovascular risk and prevent gestational diabetes. Periodic IGT/T2D rescreening is necessary, given their propensity for more rapid deterioration in glucose tolerance. Lifestyle intervention is first-line therapy for PCOS women with IGT. Metformin is an option if lifestyle intervention fails to have an impact, while bariatric surgery is reserved for a select set of morbidly obese patients.
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Affiliation(s)
- Carly E Kelley
- a Department of Medicine, Division of Endocrinology, Duke University Medical Center, DUMC 3924, 201 Trent Drive, Durham, NC 27710, USA
| | - Ann J Brown
- b Department of Medicine, Division of Endocrinology, Duke University Medical Center, DUMC 3611, 201 Trent Drive, Durham, NC 27710, USA
| | - Tracy L Setji
- c Department of Medicine, Division of Endocrinology, Duke University Medical Center, DUMC 3222, 201 Trent Drive, Durham, NC 27710, USA
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19
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Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz BO. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014; 171:P1-29. [PMID: 24849517 DOI: 10.1530/eje-14-0253] [Citation(s) in RCA: 369] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
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Affiliation(s)
- Gerard Conway
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Didier Dewailly
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Evanthia Diamanti-Kandarakis
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Héctor F Escobar-Morreale
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Stephen Franks
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Alessandra Gambineri
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Fahrettin Kelestimur
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Djuro Macut
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Dragan Micic
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Renato Pasquali
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Marija Pfeifer
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Duarte Pignatelli
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Michel Pugeat
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Bulent O Yildiz
- Department of EndocrinologyUniversity College London Hospitals, 250 Euston Road, London NW1 2BU, UKDepartment of Endocrine Gynaecology and Reproductive MedicineCentre Hospitalier de Lille, Hopital Jeanne de Fiandre, Lille, FranceEndocrine Unit3rd Department of Medicine, University of Athens Medical School, Athens, GreeceDepartment of Endocrinology and NutritionUniversidad de Alcalá and Hospital Universitario Ramón y Cajal and Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM and Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, SpainImperial College LondonInstitute of Reproductive and Developmental Biology, London, UKDivision of EndocrinologyDepartment of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyDepartment of EndocrinologySchool of Medicine, Erciyes University, Kayseri, TurkeyClinic for EndocrinologyDiabetes and Metabolic Diseases, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of EndocrinologyDiabetes and Metabolic Diseases, Medical Faculty, University Medical Centre, University of Ljubljana, Ljubljana, SloveniaDepartment of EndocrinologyFaculty of Medicine of Porto, Hospital S. Joao, Porto, PortugalInsermFédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Université Lyon-1, Lyon, France andDivision of Endocrinology and MetabolismDepartment of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
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Gooding HC, Milliren C, St Paul M, Mansfield MJ, DiVasta A. Diagnosing dysglycemia in adolescents with polycystic ovary syndrome. J Adolesc Health 2014; 55:79-84. [PMID: 24560306 DOI: 10.1016/j.jadohealth.2013.12.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 12/17/2013] [Accepted: 12/18/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE Screening for impaired glucose tolerance (IGT) is recommended for adolescents with polycystic ovary syndrome (PCOS) with oral glucose tolerance test (OGTT). Whether glycated hemoglobin (HbA1c) can be used for screening in this patient population is unknown. We sought to determine the utility of HbA1c and 2-hour OGTT for diagnosing dysglycemia in adolescents with PCOS. METHODS This was a retrospective cohort study of 68 adolescents with PCOS seen in the Boston Children's Hospital Division of Adolescent Medicine between 2008 and 2011 and not known to have diabetes. Prevalence of dysglycemia (impaired fasting glucose, IGT, increased risk for diabetes, or diabetes mellitus as diagnosed by fasting plasma glucose, 2-hour OGTT, and/or HbA1c) and sensitivity and specificity of HbA1c for diagnosing dysglycemia compared with OGTT were assessed. RESULTS Twenty-four participants had abnormal glucose testing, including one participant (1.5%) who met criteria for diabetes mellitus and 23 participants (34%) who met criteria for impaired fasting glucose/IGT/prediabetes. More patients were identified as having dysglycemia by HbA1c than OGTT. Compared with OGTT, HbA1c had a sensitivity of 60% and a specificity of 69% for diagnosing dysglycemia. CONCLUSIONS In adolescents with PCOS, HbA1c had moderate sensitivity and specificity for detecting dysglycemia compared with OGTT. Clinicians should be aware that both tests have benefits and limitations, and the optimal test for follow-up requires further study.
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Affiliation(s)
- Holly Catherine Gooding
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts.
| | - Carly Milliren
- Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts
| | - Michelle St Paul
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts
| | - M Joan Mansfield
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts
| | - Amy DiVasta
- Division of Adolescent and Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Division of Gynecology, Boston Children's Hospital, Boston, Massachusetts
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Mani H, Khunti K, Levy M, Davies MJ. Diabetes advice for women with polycystic ovary syndrome: prevention, prevention, prevention. ACTA ACUST UNITED AC 2013. [DOI: 10.2217/dmt.13.54] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Veltman-Verhulst SM, Goverde AJ, van Haeften TW, Fauser BCJM. Fasting glucose measurement as a potential first step screening for glucose metabolism abnormalities in women with anovulatory polycystic ovary syndrome. Hum Reprod 2013; 28:2228-34. [DOI: 10.1093/humrep/det226] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Huang G, Coviello A. Clinical update on screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes 2012; 19:512-9. [PMID: 23108199 DOI: 10.1097/med.0b013e32835a000e] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in premenopausal women. This review discusses the screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with PCOS, highlighting significant recent developments. RECENT FINDINGS PCOS is a complex genetic disorder with multiple susceptibility genes as well as environmental factors influencing the expression of various PCOS phenotypes. The first genome-wide association study of PCOS identified susceptibility loci on chromosome 2 near the luteinizing hormone receptor gene LHCGR and chromosome 9 near the obesity gene DEEND1A. Women with PCOS are affected by a variety of metabolic disorders, including insulin resistance, metabolic syndrome, type-2 diabetes, dyslipidemia and obesity. Recently, it has been established that women with PCOS have a high risk of nonalcoholic fatty liver disease. These metabolic disturbances are associated with an increased risk of cardiovascular disease (CVD). Although women with PCOS have higher rates of cardiovascular risk factors and intermediate markers of CVD, studies definitively documenting increased CVD are lacking. SUMMARY The high prevalence of metabolic disorders and CVD risk factors in women with PCOS highlights the need for early screening, diagnosis and treatment of these disorders to promote long-term health and possibly prevent CVD.
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Affiliation(s)
- Grace Huang
- Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA
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24
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Current world literature. Curr Opin Endocrinol Diabetes Obes 2012; 19:233-47. [PMID: 22531108 DOI: 10.1097/med.0b013e3283542fb3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Kim JJ, Choi YM, Cho YM, Jung HS, Chae SJ, Hwang KR, Hwang SS, Ku SY, Kim SH, Kim JG, Moon SY. Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome. Hum Reprod 2012; 27:1439-1444. [PMID: 22357766 DOI: 10.1093/humrep/des039] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2024] Open
Abstract
BACKGROUND Recently, the American Diabetes Association (ADA) has included glycated hemoglobin A1(c) (A1C) level as a component of diagnostic criteria of 'diabetes' or 'increased risk for diabetes'. This study was conducted to examine the prevalence of and risk factors for 'elevated A1C' (≥5.7%) in women with polycystic ovary syndrome (PCOS). METHODS A1C was measured using an immunoturbidimetric assay, and was evaluated in 154 patients with PCOS and 469 age-matched controls (match ratio of 1-3). All subjects were categorized by BMI (non-obese <25 kg/m(2) and obese ≥25 kg/m(2)), and the prevalence of elevated A1C was also analyzed according to BMI. RESULTS One-third (31.2%) of the patients with PCOS had elevated A1C. The prevalence of elevated A1C (≥5.7%) was similar in obese women with PCOS and obese controls (23.5 and 20.0%, respectively, P= 1.0) but non-obese women with PCOS (mean age 29.8 ± 5.3 years) had a higher prevalence of elevated A1C than non-obese controls (31.2 versus 6.6%, respectively, P< 0.001). Logistic regression analysis of all subjects showed that the odds that a woman has elevated A1C was 6.7 times higher if she has PCOS (adjusted odds ratio 6.67, 95% confidence interval 3.50-12.70). CONCLUSIONS The high prevalence of elevated A1C in non-obese patients with PCOS and an increased risk of elevated A1C associated with PCOS suggest that PCOS itself may be associated with abnormal A1C status. Assessing A1C level in young, non-obese patients with PCOS may be a useful new approach to screening for diabetes.
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Affiliation(s)
- Jin Ju Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
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Palomba S, Falbo A, Russo T, Rivoli L, Orio M, Cosco AG, Vero R, Capula C, Tolino A, Zullo F, Colao A, Orio F. The risk of a persistent glucose metabolism impairment after gestational diabetes mellitus is increased in patients with polycystic ovary syndrome. Diabetes Care 2012; 35:861-7. [PMID: 22338097 PMCID: PMC3308296 DOI: 10.2337/dc11-1971] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Accepted: 12/20/2011] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To test the hypothesis that the risk of persistent glucose impairment after gestational diabetes mellitus (GDM) is increased in patients with polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS The prospective case-control study included 42 pregnant patients with PCOS and GDM and 84 pregnant control patients with GDM but without clinical and biochemical hyperandrogenism, polycystic ovaries, and oligo-anovulation. The case and control subjects were matched one to two for age and BMI. The glycemic profiles were studied in all subjects 6 weeks, 12 weeks, and 18 months after delivery. The incidence and the relative risk (RR) were calculated for overall persistence of an abnormal glycemic pattern and for each specific alteration, i.e., impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus (DM). RESULTS At 18 months after delivery, the incidences of IFG, IGT, and IFG-IGT were significantly (P < 0.05) higher in the cases than in the controls. At the 18-month follow-up, the RR for the composite outcome of glucose metabolism impairment in PCOS women was 3.45 (95% CI 1.82-6.58). CONCLUSIONS Patients with PCOS are at increased risk for a persistent impaired glucose metabolism after GDM.
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Affiliation(s)
- Stefano Palomba
- Department of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Catanzaro, Italy.
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