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Farhadi‐Azar M, Noroozzadeh M, Mousavi M, Saei Ghare Naz M, Ramezani Tehrani F. Impaired glucose tolerance and insulin resistance in a prenatally-androgenized rat model of polycystic ovary syndrome in later life. Exp Physiol 2025; 110:410-423. [PMID: 39613459 PMCID: PMC11868029 DOI: 10.1113/ep091912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 10/30/2024] [Indexed: 12/01/2024]
Abstract
Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive-aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally-androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3-20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies.
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Affiliation(s)
- Mahbanoo Farhadi‐Azar
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Mahsa Noroozzadeh
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Maryam Mousavi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Marzieh Saei Ghare Naz
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
- Foundation for Research & Education ExcellenceVestavia HillsALUSA
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Pramanik S, Mondal S, Palui R, Ray S. Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management. World J Clin Pediatr 2024; 13:91587. [PMID: 38947996 PMCID: PMC11212753 DOI: 10.5409/wjcp.v13.i2.91587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 06/07/2024] Open
Abstract
Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.
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Affiliation(s)
- Subhodip Pramanik
- Department of Endocrinology, Neotia Getwel Multi-specialty hospital, Siliguri 734010, West Bengal, India
| | - Sunetra Mondal
- Department of Endocrinology, NRS Medical College and Hospital, Kolkata 700014, West Bengal, India
| | - Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Sayantan Ray
- Department of Endocrinology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar 751019, Odisha, India
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Dutil C, Podinic I, Featherstone RB, Eaton A, Sadler CM, Goldfield GS, Hadjiyannakis S, Gruber R, Tremblay MS, Prud’homme D, Chaput JP. Sleep and insulin sensitivity in adolescents at risk of type 2 diabetes: the Sleep Manipulation in Adolescents at Risk of Type 2 Diabetes randomized crossover study. Sleep 2024; 47:zsad313. [PMID: 38070132 PMCID: PMC11082473 DOI: 10.1093/sleep/zsad313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 11/01/2023] [Indexed: 01/21/2024] Open
Abstract
STUDY OBJECTIVES To investigate the effect of increasing sleep duration for 1 week, compared to a week of habitual and decreased sleep, on insulin sensitivity (IS) in adolescents at risk for type 2 diabetes (T2D). METHODS Adolescents, 13-18 years old, at risk for T2D, with obesity and other risk factors, were recruited for a randomized (1:1), open-label, sex-stratified crossover study, that manipulated time-in-bed to modify sleep duration (measured by actigraphy). Following a week of habitual (HB) sleep, time-in-bed was increased (IN) and decreased (DE) by 1 hour 30 min/night for 1 week, counterbalanced across participants (HBINDE or HBDEIN), and separated by a week of washout sleep. The main outcome measure was IS, obtained via 2-hour oral-glucose-tolerance-test conducted after each sleep week. RESULTS Of the 43 participants recruited, 36 (84%) completed all sleep interventions (52.8% female, age = 15.1 years, body mass index = 99.9th percentile, order: HBINDE = 18 and HBDEIN = 18). On average, during the HB week, participants slept 7 hours 31 min/night; sleep duration was 1 hour 02 min/night higher during the IN week and 1 hour 19 min/night lower during the DE week. We found a significant effect of sleep week on IS with a large effect size. Following the IN sleep week, IS was 20% higher compared to after the HB and DE sleep weeks, but there was no significant difference in IS following HB versus DE sleep weeks. CONCLUSIONS Whenever possible, clinicians should empower youth at risk of T2D to improve their sleep duration, since even a modest increase in sleep duration of 1 h/night for 1 week can have a positive impact on IS in this population. CLINICAL TRIALS Sleep Extension and IS in Adolescents, https://clinicaltrials.gov/study/NCT03754036, November 23rd, 2018. TRIAL REGISTRATION ClinicalTrials.gov (ID:NCT03754036).
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Affiliation(s)
- Caroline Dutil
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Irina Podinic
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Ryan B Featherstone
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
- Centre for Healthy Active Living (CHAL), Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada
| | - Amelia Eaton
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Christin M Sadler
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Gary S Goldfield
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada
| | - Stasia Hadjiyannakis
- Centre for Healthy Active Living (CHAL), Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada
| | - Reut Gruber
- Department of Psychiatry, McGill University, Montreal, QC, Canada
- Attention, Behaviour and Sleep Lab, Douglas Mental Health University Institute, Montreal, QC, Canada
| | - Mark S Tremblay
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada
| | - Denis Prud’homme
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
- Université de Moncton, Moncton, NB, Canada
| | - Jean-Philippe Chaput
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
- School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada
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Hitt TA, Hannon TS, Magge SN. Approach to the Patient: Youth-Onset Type 2 Diabetes. J Clin Endocrinol Metab 2023; 109:245-255. [PMID: 37584397 DOI: 10.1210/clinem/dgad482] [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: 05/30/2023] [Revised: 08/10/2023] [Accepted: 08/11/2023] [Indexed: 08/17/2023]
Abstract
Youth-onset type 2 diabetes is a growing epidemic with a rising incidence worldwide. Although the pathogenesis and diagnosis of youth-onset type 2 diabetes are similar to adult-onset type 2 diabetes, youth-onset type 2 diabetes is unique, with greater insulin resistance, insulin hypersecretion, and faster progression of pancreatic beta cell function decline. Individuals with youth-onset type 2 diabetes also develop complications at higher rates within short periods of time compared to adults with type 2 diabetes or youth with type 1 diabetes. The highest prevalence and incidence of youth-onset type 2 diabetes in the United States is among youth from minoritized racial and ethnic groups. Risk factors include obesity, family history of type 2 diabetes, comorbid conditions and use of medications associated with insulin resistance and rapid weight gain, socioeconomic and environmental stressors, and birth history of small-for-gestational-age or pregnancy associated with gestational or pregestational diabetes. Patients with youth-onset type 2 diabetes should be treated using a multidisciplinary model with frequent clinic visits and emphasis on addressing of social and psychological barriers to care and glycemic control, as well as close monitoring for comorbidities and complications. Intensive health behavior therapy is an important component of treatment, in addition to medical management, both of which should be initiated at the diagnosis of type 2 diabetes. There are limited but growing pharmacologic treatment options, including metformin, insulin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Although long-term outcomes are not fully known, metabolic/bariatric surgery in youth with type 2 diabetes has led to improved cardiometabolic outcomes.
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Affiliation(s)
- Talia A Hitt
- Division of Endocrinology and Diabetes, Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Room 3114, Baltimore, MD 21287, USA
| | - Tamara S Hannon
- Division of Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine, 705 Riley Hospital Drive, Indianapolis, IN 46202, USA
| | - Sheela N Magge
- Division of Endocrinology and Diabetes, Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Room 3114, Baltimore, MD 21287, USA
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The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study. J Clin Med 2023; 12:jcm12020557. [PMID: 36675485 PMCID: PMC9860755 DOI: 10.3390/jcm12020557] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 12/30/2022] [Accepted: 01/06/2023] [Indexed: 01/12/2023] Open
Abstract
The aim of this case-control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3-20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (β = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD.
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Gupta J, Antal Z, Mauer E, Gerber LM, An A, Censani M. Dysglycemia screening with oral glucose tolerance test in adolescents with polycystic ovary syndrome and relationship with obesity. BMC Endocr Disord 2022; 22:180. [PMID: 35842601 PMCID: PMC9288674 DOI: 10.1186/s12902-022-01098-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 07/08/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Adolescents with polycystic ovary syndrome (PCOS) are at increased risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus. The aim of this study is to evaluate dysglycemia and biochemical differences based on BMI status and assess the prognostic ability of elevated hemoglobin A1c (HbA1c) in predicting an abnormal 2 hour oral glucose tolerance test (OGTT). METHODS Retrospective cohort of female patients aged 11-18 years who underwent 75-g OGTT and were evaluated for PCOS at an urban tertiary care hospital between January 2002 to December 2017. RESULTS In 106 adolescents with PCOS who had OGTT results available, IGT was markedly pronounced in the ≥95th percentile BMI group (17 out of 72; 23.6%) compared with <95th percentile BMI group (4 out of 34; 11.7%). One patient with obesity met the criteria for type 2 diabetes. Patients with obesity had significantly higher homeostasis model assessment (HOMA-IR) and lower whole body insulin sensitivity index (WBISI) (p < 0.001) compared to patients without obesity. Free testosterone levels were also higher in patients with obesity (p< 0.03) and were significantly associated with HOMA-IR when controlling for body mass index (BMI). HbA1c did not demonstrate a strong ability to predict abnormal OGTT on receiver operating characteristic (ROC) curve analysis [Area under the curve (AUC) = 0.572, 95% CI: 0.428, 0.939]). CONCLUSIONS In a study to assess glucose abnormalities in adolescents with PCOS, IGT was found to be markedly increased in patients with obesity, with abnormal glucose metabolism identified in over one-fifth of the patients. HbA1c alone may be a poor test to assess IGT and we recommend that adolescents diagnosed with PCOS and obesity undergo formal oral glucose tolerance testing.
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Affiliation(s)
- Jyotsna Gupta
- Department of Pediatrics, Division of Pediatric Endocrinology, New York Presbyterian Hospital, Weill Cornell Medicine, 505 East 70th Street, New York, NY, USA
| | - Zoltan Antal
- Department of Pediatrics, Division of Pediatric Endocrinology, New York Presbyterian Hospital, Weill Cornell Medicine, 505 East 70th Street, New York, NY, USA
| | - Elizabeth Mauer
- Department of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, USA
| | - Linda M Gerber
- Department of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, USA
| | - Anjile An
- Department of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine, 1300 York Avenue, New York, NY, USA
| | - Marisa Censani
- Department of Pediatrics, Division of Pediatric Endocrinology, New York Presbyterian Hospital, Weill Cornell Medicine, 505 East 70th Street, New York, NY, USA.
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Kiconco S, Tay CT, Rassie KL, Azziz R, Teede HJ, Joham AE. Natural history of polycystic ovary syndrome: A systematic review of cardiometabolic outcomes from longitudinal cohort studies. Clin Endocrinol (Oxf) 2022; 96:475-498. [PMID: 34894357 DOI: 10.1111/cen.14647] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/08/2021] [Accepted: 11/21/2021] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Women with polycystic ovary syndrome (PCOS) have a worsened metabolic profile but the progression of cardiometabolic features over time is unclear. Understanding this natural history is a key priority in PCOS research and vital for guiding the prevention and management of this common condition. We explored cardiometabolic changes that are observed in women with PCOS compared to those without PCOS across the life course. DESIGN, PATIENTS AND MEASUREMENTS A systematic review of longitudinal cohort studies was conducted across MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews between 15 January 2020 and 11 February 2021. Eligible studies included participants with or without PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) criteria. We included studies that were published from the year 1990 to 2021 with data on cardiometabolic outcomes as per the PCOS core outcomes set. RESULTS There were 31 longitudinal studies with 28,316 participants from four continents. At the start of follow up, participants were aged between 1 year and 49 years with a follow-up period ranging from 2 to 32 years. Changes in BMI and the risk of coronary heart disease were similar in adult women with and without PCOS. Women with PCOS had a higher risk of Type 2 diabetes than their non-PCOS counterparts. Evidence for the majority of all other outcomes was conflicting and with inadequate data. CONCLUSION Understanding the natural history of PCOS and particularly changes in cardiometabolic features remains challenging. Existing literature is extensive but heterogeneous and inconsistent. Longitudinal studies in unselected populations are needed to provide high-quality data in this area.
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Affiliation(s)
- Sylvia Kiconco
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
| | - Chau T Tay
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
- Department of Endocrinology and Diabetes, Monash Health, Clayton, Victoria, Australia
| | - Kate L Rassie
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
| | - Ricardo Azziz
- Department of Obstetrics and Gynecology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Department of Healthcare Organization and Policy, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
- Department of Health Policy, Management, and Behaviour, School of Public Health, University at Albany, SUNY. Rensselaer, New York, New York, USA
| | - Helena J Teede
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
- Department of Endocrinology and Diabetes, Monash Health, Clayton, Victoria, Australia
| | - Anju E Joham
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
- Department of Endocrinology and Diabetes, Monash Health, Clayton, Victoria, Australia
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Šumarac-Dumanović M, Stamenković-Pejković D, Jeremić D, Dumanović J, Mandić-Marković V, Žarković M, Micić D. Age, Body Mass Index, and Waist-to-Hip Ratio Related Changes in Insulin Secretion and Insulin Sensitivity in Women with Polycystic Ovary Syndrome: Minimal Model Analyses. Int J Endocrinol 2022; 2022:6630498. [PMID: 35646110 PMCID: PMC9132706 DOI: 10.1155/2022/6630498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 02/21/2022] [Accepted: 04/07/2022] [Indexed: 11/29/2022] Open
Abstract
Insulin resistance is believed to be an integral component of the polycystic ovary syndrome (PCOS). Beta (ß) cell dysfunction is also found in PCOS. In the study, we determined the influence of age, body mass index (BMI), and waist-to-hip ratio (WHR) on insulin response to oral glucose load (OGTT) and on insulin sensitivity (Si) and ß-cell function in young women with PCOS. One hundred fourteen patients with PCOS and 41 controls with normal basal plasma glucose were studied. A 75-g OGTT was performed to determine glucose tolerance and insulin response. Insulin sensitivity and ß-cell function were studied using a modified frequently sampled IV glucose tolerance test (FISGTT) to determine the acute insulin response (AIRG), as well as Si by minimal model analysis. Si was decreased in PCOS women (2.49 0.18 vs. 3.41 ± 0.36, p < 0.05), but no difference in AIRG existed between the PCOS and control group (75.1 ± 4.6 vs. 63.4 ± 4.6, p < 0.05). BMI and WHR correlated negatively with Si (r = -0.43; r = -0.289, p < 0.001, respectively), but not with AIRG (r = 0.116; r = -0.02, p > 0.05, respectively). Increasing age correlated negatively with AIRG (r = -0.285, p < 0.001). There was a significant interaction between disease (PCOS), BMI, and WHR on Si as well as between age and PCOS on AIRG. Thus, patients below the age of 25 with PCOS showed enhanced AIRG (89.5 ± 7.1 vs. 65.1 ± 6.7, p < 0.05) and decreased Si (2.43 ± 0.25 vs. 4.52 ± 0.62, p < 0.05) compared to age-matched controls. In conclusion, these data suggest that not all patients with PCOS have basal and stimulated hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Based on these data in young PCOS subjects, the development of insulin resistance and T2DM may be prevented with appropriate treatment strategies.
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Affiliation(s)
- Mirjana Šumarac-Dumanović
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
| | - Danica Stamenković-Pejković
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
| | - Danka Jeremić
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
| | - Janko Dumanović
- Obstetrics and Gynaecology Clinic Narodni Front, Belgrade, Serbia
| | - Vesna Mandić-Marković
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Obstetrics and Gynaecology Clinic Narodni Front, Belgrade, Serbia
| | - Miloš Žarković
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
| | - Dragan Micić
- Department of Medical Sciences, Serbian Academy of Sciences and Arts, Belgrade, Serbia
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Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome. Genet Res (Camb) 2021; 2021:7781823. [PMID: 34949963 PMCID: PMC8668318 DOI: 10.1155/2021/7781823] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 11/06/2021] [Accepted: 11/17/2021] [Indexed: 12/14/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.
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Laru J, Nedelec R, Koivuaho E, Ojaniemi M, Järvelin MR, Tapanainen JS, Franks S, Tolvanen M, Piltonen TT, Sebert S, Morin-Papunen L. BMI in childhood and adolescence is associated with impaired reproductive function-a population-based cohort study from birth to age 50 years. Hum Reprod 2021; 36:2948-2961. [PMID: 34364312 PMCID: PMC8643422 DOI: 10.1093/humrep/deab164] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 06/08/2021] [Indexed: 11/12/2022] Open
Abstract
STUDY QUESTION What is the association between childhood and adolescent BMI and reproductive capacity in women? SUMMARY ANSWER Adolescent girls with obesity had an increased risk of infertility and childlessness in adulthood independently of their marital status or the presence of polycystic ovary syndrome (PCOS). WHAT IS KNOWN ALREADY Girls with obesity (BMI (kg/m2)>95th percentile) more often exhibit menstrual irregularities and infertility problems as compared to those with normal weight, and premenarcheal girls with obesity have an increased risk of childlessness and infertility in adulthood. Follow-up studies on the relation between childhood and adolescence growth patterns and fertility or parity throughout the reproductive life span are limited. STUDY DESIGN, SIZE, DURATION A prospective, population-based cohort study (the Northern Finland birth cohort 1966) was performed with 5889 women born in 1966 and followed from birth to age 50 years. Postal questionnaires at ages 31 and 46 years addressed questions on reproductive capacity evaluated by decreased fecundability, need for infertility assessment and treatment by 46 years of age. Childlessness and number of children by age 50 years were recovered from registers. Women who did not report ever having attempted to achieve pregnancy (n = 1507) were excluded. The final study population included 4382 women who attempted to achieve pregnancy before age 46 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on BMI were collected by trained personnel at all stages. We assessed association with both prospectively measured BMI at various time points and with early adiposity phenotypes derived from linear mixed models including the timing and the BMI at adiposity peak (AP) and adiposity rebound (AR). Self-reported infertility assessments and treatments were assessed at ages 31 and 46 years. Data on deliveries were collected from the national birth register. Decreased fecundability was defined at age 31 years as time to achieve pregnancy over 12 months. Logistic regression analyses were conducted with adjustments for marital status, education level and smoking at age 31 years. Women with PCOS were excluded from stratification-based sensitivity analyses. Obesity at a specific age group was defined by having at least one BMI value above the 95th percentile during the related period. MAIN RESULTS AND THE ROLE OF CHANCE BMI at the age of AR (5-7 years) was not associated with fertility outcomes after adjustments, but girls with AR <5.1 years had a higher risk of remaining childless compared to girls with AR over 5.1 years (adjusted odds ratio (OR): 1.45 (1.10-1.92)). At ages 7-10 and 11-15 years, obesity was associated with decreased fecundability (adjusted OR 2.05 (1.26-3.35) and 2.04 (1.21-3.44), respectively) and a lower number of children. At age 11-15 years, both overweight and obesity were associated with a higher risk of childlessness (adjusted OR 1.56 (1.06-2.27), 1.77 (1.02-3.07), respectively), even after excluding women with PCOS. Underweight at age 11-15 years was associated with an increased risk for infertility treatment (adjusted OR 1.55 (1.02-2.36)) and a tendency for an increased risk for infertility assessment (adjusted OR 1.43 (0.97-2.10)) after excluding women with PCOS. LIMITATIONS, REASON FOR CAUTION Despite a high participation rate throughout the follow-up, some growth data for children over the different age groups were missing. Infertility outcomes were self-reported. A potential over-diagnosis of obesity may have reduced the significance of the association between childhood obesity and fertility outcomes, and the diagnosis of PCOS was self-reported. WIDER IMPLICATIONS OF THE FINDINGS This study supports previous results showing that girls with obesity in late childhood and in adolescence displayed reduced fertility and an increased risk of remaining childless in adulthood, independently of marital history and PCOS in adulthood. These findings corroborate the body of evidence for a causal relation between early adiposity and the reproductive functions in women. We recommend reinforcing the prevention of obesity in school-age girls to reduce the risk of impaired reproductive functions. STUDY FUNDING/COMPETING INTEREST(S) NFBC1966 received financial support from University of Oulu Grant no. 65354, Oulu University Hospital Grant no. 2/97, 8/97, Ministry of Health and Social Affairs Grant no. 23/251/97, 160/97, 190/97, National Institute for Health and Welfare, Helsinki Grant no. 54121, Regional Institute of Occupational Health, Oulu, Finland Grant no. 50621, 54231. The Finnish Medical Foundation, the North Ostrobothnia Regional Fund, the Academy of Finland (project grants 315921, 104781, 120315, 129269, 1114194, 24300796), Center of Excellence in Complex Disease Genetics and SALVE, the Sigrid Juselius Foundation, Biocenter Oulu, University Hospital Oulu and University of Oulu (75617), Jalmari ja Rauha Ahokkaan säätiö, The Finnish Medical Foundation, Medical Research Center Oulu, National Institute for Health Research (UK). M. R. J., S. S. and R. N. received funding by the Academy of Finland (#268336) and the European Union's Horizon 2020 research and innovation program (under Grant agreement no. 633595 for the DynaHEALTH action and GA 733206 for LifeCycle). The funders had no role in study design, in the collection, analysis and interpretation of the data, in the writing of the article and in the decision to submit it for publication. The authors have no conflict of interest to disclose. TRIAL REGISTRATION NUMBER N/A.
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Grants
- 54121 Department of Health
- Medical Research Council
- University of Oulu
- Oulu University Hospital
- Ministry of Health and Social Affairs
- National Institute for Health and Welfare, Helsinki
- Regional Institute of Occupational Health, Oulu, Finland
- The Finnish Medical Foundation, the North Ostrobothnia Regional Fund, the Academy of Finland
- Center of Excellence in Complex Disease Genetics and SALVE, the Sigrid Juselius Foundation, Biocenter Oulu, University Hospital Oulu and University of Oulu
- Jalmari ja Rauha Ahokkaan säätiö
- The Finnish Medical Foundation, Medical Research Center Oulu, National Institute for Health Research (UK)
- Academy of Finland
- European Union’s Horizon 2020 research and innovation program
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Affiliation(s)
- J Laru
- Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
| | - R Nedelec
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
| | - E Koivuaho
- Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
| | - M Ojaniemi
- Department of Children and Adolescents, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
| | - M -R Järvelin
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
- Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK
- Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
| | - J S Tapanainen
- Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - S Franks
- Institute of Reproductive and Developmental Biology, Imperial College London, London, UK
| | - M Tolvanen
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
| | - T T Piltonen
- Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
| | - S Sebert
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
| | - L Morin-Papunen
- Department of Obstetrics and Gynaecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
- Correspondence address. PEDEGO Research Unit, Department of Obstetrics and Gynecology, Medical Research Center, Oulu University Hospital, University of Oulu, Kajaanintie 50, BOX 5000, 90014 Oulu, Finland. Tel: +358 8 3154109; E-mail: https://orcid.org/0000-0001-5987-7534
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Dondi E, Tufano M, Vigone MC, Lucaccioni L, Pozzobon G, Ubertini G, Mozzillo E, Delvecchio M. Polycystic ovary syndrome in pediatric obesity and diabetes. Minerva Pediatr (Torino) 2021; 73:523-536. [PMID: 34286948 DOI: 10.23736/s2724-5276.21.06542-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Polycystic ovary syndrome is characterized by anovulation (amenorrhea, oligomenorrhea, irregular menstrual cycles) combined with symptoms of androgen excess (hirsutism, acne, alopecia). The clear definition and diagnosis in adolescents could be challenging considering that most of symptoms occur as part of the expected physiological hormonal imbalance of puberty. Therefore, different diagnostic criteria have been elaborated. Polycystic ovary syndrome could be associated to obesity, diabetes mellitus, and metabolic syndrome. In adolescents with polycystic ovary syndrome, adiposity is associated with higher androgen concentrations and greater menstrual irregularity. Polycystic ovary syndrome in youth is considered a risk factor for type 2 diabetes mellitus in adulthood. On the other hand, increased prevalence of polycystic ovary syndrome has been shown in type 1 diabetes mellitus. EVIDENCE The treatment of polycystic ovary syndrome in adolescents is controversial considering that adequate trials are lacking. First line treatment comprises lifestyle modification (preferably multicomponent including diet, exercise and behavioural strategies) that should be recommended overall in the patients with polycystic ovary syndrome and overweight, central obesity and insulin resistance. Beyond non-pharmacological therapy, pharmacological agents include combined hormonal contraceptives, metformin and antiandrogens, used separately or in combination. The aim of therapy is to bring back ovulation, to normalize menses, to reduce hirsutism and acne, to reduce weight. Other important goal is the treatment of hyperlipidaemia and of hyperglycaemia. CONCLUSIONS This narrative review aims to review the most pertinent literature about polycystic ovary syndrome in adolescents with obesity or diabetes. We overviewed the diagnostic criteria, the pathophysiology and the possible treatment approaches.
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Affiliation(s)
- Elena Dondi
- Department of Pediatrics, S. Andrea Hospital, Vercelli, Italy
| | - Maria Tufano
- Department of Pediatrics and Neonatology, Usl Central Tuscany, Florence, Prato, Italy
| | - Maria C Vigone
- Department of Pediatrics, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Lucaccioni
- Pediatric Unit, Departmente of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Gabriella Pozzobon
- Department of Pediatrics, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Enza Mozzillo
- Section of Pediatrics, Department of Translational Medical Science, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy
| | - Maurizio Delvecchio
- Metabolic Disorders and Genetic Unit, Giovanni XXIII Children Hospital, Bari, Italy -
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Kamrul-Hasan ABM, Aalpona FTZ, Selim S. Clinical, Metabolic and Hormonal Profiles of Bangladeshi Adolescents with Polycystic Ovary Syndrome. TOUCHREVIEWS IN ENDOCRINOLOGY 2021; 17:54-58. [PMID: 35118446 PMCID: PMC8320016 DOI: 10.17925/ee.2021.17.1.54] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/24/2020] [Indexed: 01/21/2023]
Abstract
Background: The features of polycystic ovary syndrome (PCOS) vary greatly among adolescent girls and adult women. Some of the features of PCOS may overlap with features of normal pubertal development in girls. Methods: This cross-sectional study was conducted among adolescents newly diagnosed with PCOS attending a tertiary hospital in Bangladesh. The relevant clinical, metabolic and hormonal profiles of 175 participants were evaluated. Results: The mean age of the study participants was 16.8 (±1.7) years. Oligomenorrhea was the predominant menstrual irregularity (88%). More than one-quarter of participants (27.4%) had a first-degree relative with PCOS, and 12% had a first-degree relative with type 2 diabetes. More than three-quarters (77.7%) had acanthosis nigricans. The majority (69.1%) were overweight (29.7%) or obese (39.4%), whereas 6.3% were underweight. A total of 65.7% had abdominal obesity. One-fifth (20%) of participants had pre-hypertension, and 3.4% were hypertensive. Around one-quarter (24%) had abnormal glucose tolerance (prediabetes 21.1%, diabetes 2.9%) and the majority (90.9%) had dyslipidaemia. The median Ferriman-Gallwey score was 12, 94.9% of participants had hirsutism and 33.7% had biochemical hyperandrogenism. Metabolic syndrome was present in 42.3% of participants. Higher body mass index and presence of hirsutism were associated with higher risks of metabolic syndrome. Conclusions: The clinical, metabolic and hormonal profiles of Bangladeshi adolescents with PCOS highlight risk factors and the need for clinical vigilance with respect to metabolic disease.
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Affiliation(s)
- ABM Kamrul-Hasan
- Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
| | - Fatema Tuz Zahura Aalpona
- Outpatient Department, Gynaecology & Obstetrics, Mymensingh Medical College Hospital, Mymensingh, Bangladesh
| | - Shahjada Selim
- Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
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Daghestani MH, Omair M, Daghestani M, Abdel-Razeq SS, Kaya N, Warsy A. Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric, hormonal and lipid profiles in polycystic ovarian syndrome. J Med Biochem 2021; 40:74-85. [PMID: 33584143 PMCID: PMC7857854 DOI: 10.5937/jomb0-26183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/23/2020] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Polycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters. METHODS Saudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced. RESULTS The waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development. CONCLUSIONS The rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.
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Affiliation(s)
- Maha H. Daghestani
- King Saud University, Center for Female Scientific and Medical Colleges, Department of Zoology, Saudi Arabia
| | - Maha Omair
- King Saud University, College of Science, Department of Statistics and Operations Research, Saudi Arabia
| | - Mazin Daghestani
- Umm-Al-Qura University, Department of Obstetrics & Gynecology, Saudi Arabia
| | - Sonya S. Abdel-Razeq
- Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, New Haven, CT, USA
| | - Namik Kaya
- King Faisal Specialist Hospital and Research Center, Department of Genetics, Riyadh, Saudi Arabia
| | - Arjumand Warsy
- King Saud University, Center for Female Scientific and Medical Colleges, Central Laboratory, Riyadh, Saudi Arabia
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Ding H, Zhang J, Zhang F, Zhang S, Chen X, Liang W, Xie Q. Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 2021; 12:741764. [PMID: 34745009 PMCID: PMC8564180 DOI: 10.3389/fendo.2021.741764] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/22/2021] [Indexed: 01/27/2023] Open
Abstract
PCOS has a wide range of negative impacts on women's health and is one of the most frequent reproductive systemic endocrine disorders. PCOS has complex characteristics and symptom heterogeneity due to the several pathways that are involved in the infection and the absence of a comm14on cause. A recent study has shown that the main etiology and endocrine aspects of PCOS are the increased level of androgen, which is also known as "hyperandrogenemia (HA)" and secondly the "insulin resistance (IR)". The major underlying cause of the polycystic ovary is these two IR and HA, by initiating the disease and its severity or duration. As a consequence, study on Pathogenesis is crucial to understand the effect of "HA" and "IR" on the pathophysiology of numerous symptoms linked to PCOS. A deep understanding of the pattern of the growth in PCOS for HA and IR can help ameliorate the condition, along with adjustments in nutrition and life, as well as the discovery of new medicinal products. However, further research is required to clarify the mutual role of IR and HA on PCOS development.
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Affiliation(s)
- Haigang Ding
- Department of Gynecology, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China
- Obstetrics and Gynecology Hospital of Shaoxing University, Shaoxing, China
| | - Juan Zhang
- Department of Gynecology, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China
- Obstetrics and Gynecology Hospital of Shaoxing University, Shaoxing, China
| | - Feng Zhang
- Department of Gynecology, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China
- Obstetrics and Gynecology Hospital of Shaoxing University, Shaoxing, China
| | - Songou Zhang
- College of Medicine, Shaoxing University, Shaoxing, China
| | - Xiaozhen Chen
- College of Medicine, Shaoxing University, Shaoxing, China
| | - Wenqing Liang
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
- *Correspondence: Qiong Xie, ; Wenqing Liang,
| | - Qiong Xie
- Department of Gynecology, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, China
- *Correspondence: Qiong Xie, ; Wenqing Liang,
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Rosenfield RL, Cooke DW, Radovick S. Puberty in the Female and Its Disorders. SPERLING PEDIATRIC ENDOCRINOLOGY 2021:528-626. [DOI: 10.1016/b978-0-323-62520-3.00016-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Kamrul-Hasan ABM, Aalpona FTZ, Selim S. Clinical, Metabolic and Hormonal Profiles of Bangladeshi Adolescents with Polycystic Ovary Syndrome. EUROPEAN ENDOCRINOLOGY 2021. [DOI: 10.17925/ee.2021.1.1.54] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Savic Hitt TA, Katz LEL. Pediatric Type 2 Diabetes: Not a Mini Version of Adult Type 2 Diabetes. Endocrinol Metab Clin North Am 2020; 49:679-693. [PMID: 33153674 PMCID: PMC7772966 DOI: 10.1016/j.ecl.2020.08.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Pediatric type 2 diabetes mellitus (T2DM) is increasing in incidence, with risk factors including obesity, puberty, family history of T2DM in a first-degree or second-degree relative, history of small-for-gestational-age at birth, child of a gestational diabetes pregnancy, minority racial group, and lower socioeconomic status. The pathophysiology of T2DM consists of insulin resistance and progression to pancreatic beta-cell failure, which is more rapid in pediatric T2DM compared with adult T2DM. Treatment options are limited. Treatment failure and nonadherence rates are high in pediatric T2DM; therefore, early diagnosis and treatment and new pharmacologic options and/or effective behavioral interventions are needed.
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Affiliation(s)
- Talia Alyssa Savic Hitt
- Division of Endocrinology & Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, Buerger Building -12th Floor, Philadelphia, PA 19104, USA.
| | - Lorraine E Levitt Katz
- Division of Endocrinology & Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, Buerger Building -12th Floor, Philadelphia, PA 19104, USA
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de Medeiros SF, de Medeiros MAS, Barbosa BB, Yamamoto MMW, Maciel GAR. Comparison of metabolic and obesity biomarkers between adolescent and adult women with polycystic ovary syndrome. Arch Gynecol Obstet 2020; 303:739-749. [PMID: 33201375 DOI: 10.1007/s00404-020-05867-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 10/31/2020] [Indexed: 01/27/2023]
Abstract
PURPOSE Knowledge of adolescent and adult phenotypes of women with polycystic ovary syndrome (PCOS) might drive opportune management. The aim of this study was to compare metabolic and obesity biomarkers between adolescent and adult women with PCOS. METHODS This observational study compared biomarkers of obesity and metabolism derangements between adolescent (n = 62) and adult (n = 248) women with PCOS. Predictors of metabolic syndrome (MS) were investigated using univariate and multivariate binary logistic regression analysis. RESULTS The postmenarcheal age of adolescents was 4.9 ± 0.03 years. Systolic blood pressure was lower in adolescents than in adults (112.3 mmHg vs 117.0 mmHg, p = 0.001) Diastolic blood pressure was also lower in adolescents (70.7 mmHg vs 75.8 mmHg, p < 0.001). Glucose intolerance (12.0% vs 19.3%) and insulin resistance (18.2% vs 17.7%) were similar in both groups (p > 0.05, for comparisons). Impaired fasting glucose was lower in adolescents (1.8% vs 11.6%, p = 0.015). Total cholesterol and low-density lipoprotein cholesterol were lower in adolescents (p < 0.001). MS in adolescents and adults were found in 10.3% and 27.8%, respectively (p = 0.005). Visceral adiposity index (VAI) was a good predictor of MS in both adolescents (OR = 12.2), and adults (OR = 9.7). CONCLUSIONS Most biomarkers of glucose metabolism abnormalities were similar in adolescents and adults with PCOS. The prevalence of MS was lower in adolescents. VAI was a strong predictor of metabolic syndrome, both in adolescent and adult women with PCOS.
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Affiliation(s)
- Sebastião Freitas de Medeiros
- Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, MT, 78 043 306, Brazil.
- Tropical Institute of Reproductive Medicine, Cuiabá, MT, Brazil.
| | | | | | | | - Gustavo Arantes Rosa Maciel
- Disciplina de Ginecologia, Departamento de Obstetrícia E Ginecologia, Faculdade de Medicina de São Paulo, Hospital das Clínicas, São Paulo, Brazil
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Al Khalifah RA, Florez ID, Zoratti MJ, Dennis B, Thabane L, Bassilious E. Efficacy of Treatments for Polycystic Ovarian Syndrome Management in Adolescents. J Endocr Soc 2020; 5:bvaa155. [PMID: 33324861 PMCID: PMC7724745 DOI: 10.1210/jendso/bvaa155] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Indexed: 02/07/2023] Open
Abstract
Limited evidence on treatment options for polycystic ovarian syndrome (PCOS) has led to considerable variation in health care practices. We aimed to compare the effects of metformin and/or oral contraceptive pills (OCP) in combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions among adolescents aged 11 to 19 years with PCOS. Literature searches were performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials from database inception through December 2018, with no language restriction. Two reviewers screened titles and abstracts, assessed full text eligibility, and extracted information from eligible trials. Evidence was synthesized through network meta-analyses (NMA) using a Bayesian random-effects approach. We identified 37 randomized controlled trials, in which 2400 patients were randomized. NMA showed no statistically important difference among all interventions to improve menstrual regulation or body mass index. Moderate-quality evidence showed hirsutism scores were reduced by multiple interventions that included single and combination medications namely; lifestyle intervention, metformin, OCP, spironolactone, pioglitazone, metformin-OCP, metformin-spironolactone, and metformin-flutamide against placebo. Moderate-quality evidence showed OCP results in more dysglycemia compared to metformin (odds ratio, 2.98; 95% credible interval, 1.02-8.96), no intervention resulted in dysglycemia reduction. In conclusion, metformin and OCP as monotherapy or in combination with other interventions compared with placebo can reduce hirsutism scores, but none of these medications lead to effective menstrual cycle regulation or weight reduction. However, the use of OCP leads to worse cardiometabolic risk factors. Further research into new treatment options is urgently needed. PROSPERO registration number CRD42015016148.
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Affiliation(s)
- Reem A Al Khalifah
- Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, College of Medicine, King Saud University, Riyadh, Saudi Arabia.,Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Ivan D Florez
- Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.,Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia
| | - Michael J Zoratti
- Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Brittany Dennis
- Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.,Department of medicine, McMaster University, Hamilton, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.,Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Department of Pediatrics and Anesthesia, McMaster University, Hamilton, Ontario, Canada
| | - Ereny Bassilious
- Department of Pediatrics, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada
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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: 17] [Impact Index Per Article: 3.4] [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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22
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Luo P, Zhang C, He Y, Yang G, Liu H, Li L. Several Circulating Biomarkers for PCOS Diagnosis. Exp Clin Endocrinol Diabetes 2019; 129:705-712. [PMID: 31683329 DOI: 10.1055/a-1025-3711] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIMS Irisin, Betatrophin and Zinc-α2-glycoprotein (ZAG) have been shown to be associated with insulin resistance (IR) and polycystic ovary syndrome (PCOS), respectively. The purpose of this study is to explore the potential accuracy of this combination of three cytokines in screening PCOS. METHODS 186 individuals were recruited for this study. Circulating Irisin, Betatrophin and ZAG concentrations were measured by enzyme-linked immunosorbent assay. The association between these serum biomarkers and PCOS was assessed by logistic regression analysis. Receiver operating curve (ROC) analysis was performed to evaluate the diagnostic value of these biomarkers for PCOS women. RESULTS In women with PCOS, serum Irisin and Betatrophin levels were markedly elevated compared to those in healthy controls (p<0.01), while ZAG levels were lower (p<0.01). PCOS women with IR (M-value<6.28) had lower circulating ZAG concentrations, and higher circulating Irisin and Betatrophin levels relative to PCOS women without IR (M-value ≥ 6.28). ROC curve analyses showed that the AUC for Irisin, ZAG and Betatrophin for predicting PCOS were 0.77, 0.83 and 0.85, respectively. In a joint ROC curves analysis of these serum markers and other parameters, the results showed that the AUC was 0.93, and the sensitivity and specificity were 82.1 % and 92.3 %, respectively. CONCLUSIONS When compared to using single cytokine, the analysis of Irisin, ZAG and Betatrophin elevates the accuracy in diagnosing PCOS.
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Affiliation(s)
- Peiqi Luo
- Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Cheng Zhang
- Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.,The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
| | - Yirui He
- Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Gangyi Yang
- Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hua Liu
- Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Ling Li
- Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
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23
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Polycystic Ovary Syndrome in Adolescence. Med Sci (Basel) 2019; 7:medsci7100101. [PMID: 31581747 PMCID: PMC6835615 DOI: 10.3390/medsci7100101] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 09/23/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females, and is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology based on ultrasound. Controversy surrounds the optimum diagnosis and management in the adolescent population. Many patients with adult PCOS present with pathognomonic symptoms as adolescents, and there is value in early diagnosis due to the associated long-term metabolic and reproductive health sequalae. A definitive diagnosis does not need to be made prior to implementing treatment in this group of young women. The practitioner who has an adolescent presenting with signs and symptoms of PCOS, has a unique opportunity to risk stratify, screen for co-morbidities, and implement early management strategies, many of which are lifestyle modifications, to help prevent long term morbidity associated with this disease.
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24
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Witchel SF, Oberfield SE, Peña AS. Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls. J Endocr Soc 2019; 3:1545-1573. [PMID: 31384717 PMCID: PMC6676075 DOI: 10.1210/js.2019-00078] [Citation(s) in RCA: 278] [Impact Index Per Article: 46.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 05/30/2019] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hyperandrogenism and chronic anovulation. Depending on diagnostic criteria, 6% to 20% of reproductive aged women are affected. Symptoms of PCOS arise during the early pubertal years. Both normal female pubertal development and PCOS are characterized by irregular menstrual cycles, anovulation, and acne. Owing to the complicated interwoven pathophysiology, discerning the inciting causes is challenging. Most available clinical data communicate findings and outcomes in adult women. Whereas the Rotterdam criteria are accepted for adult women, different diagnostic criteria for PCOS in adolescent girls have been delineated. Diagnostic features for adolescent girls are menstrual irregularity, clinical hyperandrogenism, and/or hyperandrogenemia. Pelvic ultrasound findings are not needed for the diagnosis of PCOS in adolescent girls. Even before definitive diagnosis of PCOS, adolescents with clinical signs of androgen excess and oligomenorrhea/amenorrhea, features of PCOS, can be regarded as being "at risk for PCOS." Management of both those at risk for PCOS and those with a confirmed PCOS diagnosis includes education, healthy lifestyle interventions, and therapeutic interventions targeting their symptoms. Interventions can include metformin, combined oral contraceptive pills, spironolactone, and local treatments for hirsutism and acne. In addition to ascertaining for associated comorbidities, management should also include regular follow-up visits and planned transition to adult care providers. Comprehensive knowledge regarding the pathogenesis of PCOS will enable earlier identification of girls with high propensity to develop PCOS. Timely implementation of individualized therapeutic interventions will improve overall management of PCOS during adolescence, prevent associated comorbidities, and improve quality of life.
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Affiliation(s)
- Selma Feldman Witchel
- UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sharon E Oberfield
- Division of Pediatric Endocrinology, Columbia University Medical Center, New York–Presbyterian Morgan Stanley Children’s Hospital, New York, New York
| | - Alexia S Peña
- Robinson Research Institute, University of Adelaide, North Adelaide, South Australia, Australia
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25
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Long J, Li L, Wang F, Yang G, Cheng W, Wei J, Chen M, Liu D. Screening for a Simple and Effective Indicator of Insulin Resistance in Chinese Reproductive-Aged Women, with the Insulin Clamp Technique as a Reference. Metab Syndr Relat Disord 2019; 17:423-429. [PMID: 31305214 DOI: 10.1089/met.2019.0019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: Applying the hyperinsulinemic-euglycemic clamp to estimate insulin resistance (IR) is accurate but time-consuming, so identifying a simple and effective index for IR is vitally important. The present study aimed to compare the lipid accumulation product (LAP), visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR), and Chinese visceral adiposity index (CVAI) using the hyperinsulinemic-euglycemic clamp as a reference and to screen a simple and effective indicator for IR in Chinese women of childbearing age. Methods: The present study included a cross-sectional study of 537 reproductive-aged women and an interventional study of 90 randomly chosen polycystic ovarian syndrome (PCOS) women. Physical, laboratory, and hyperinsulinemic-euglycemic clamp were completed, and the BMI, WC, LAP, VAI, CVAI, and HOMA-IR were calculated. A linear correlation and a receiver operating characteristic curve were performed. After intervention with metformin, the effects were estimated in the third month. Results: PCOS women had worse glycometabolism, serum lipid metabolism and IR, and higher prevalence rates of metabolic disorders than those without PCOS. The CVAI was strongly associated with the M value (r = -0.6953, P < 0.0001) and outperformed other parameters with the largest area under the curve (0.903) and Youden index (71.07%) for IR diagnosis in Chinese reproductive-aged women, and the diagnostic point was >28.5. After 3 months of metformin therapy, IR improved with remarkable increases in M value and reductions in the CVAI. Conclusion: The CVAI can be used as an appropriate surrogate indicator for the hyperinsulinemic-euglycemic clamp to identify IR in Chinese women of childbearing age. The interventional trial part of this study has been registered as a clinical trial (no. ChiCTR-IIR-16007901).
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Affiliation(s)
- Jiangchuan Long
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lingou Li
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.,The Department of Endocrinology, The First People's Hospital of Liangjiang New District, Chongqing, China
| | - Feng Wang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Gangyi Yang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Cheng
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jie Wei
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dongfang Liu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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26
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Nath CK, Barman B, Das A, Rajkhowa P, Baruah P, Baruah M, Baruah A. Prolactin and thyroid stimulating hormone affecting the pattern of LH/FSH secretion in patients with polycystic ovary syndrome: A hospital-based study from North East India. J Family Med Prim Care 2019; 8:256-260. [PMID: 30911516 PMCID: PMC6396624 DOI: 10.4103/jfmpc.jfmpc_281_18] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is one of the most important endocrinal diseases in reproductive age group, clinically manifested by hyperandrogenism and anovulation and different other metabolic disturbances that may have important implications for long-term health. Aim and Objective: The aim of this study was to determine the incidence of abnormal luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio in women with polycystic ovary and to assess the influence of prolactin and thyroid-stimulating hormone (TSH) in the elevated LH/FSH ratio. Study Design: Retrospective observational study. Materials and Methods: Eighty-five women in reproductive age diagnosed with PCOS between June 2012 to June 2014 at the Department of Obstetrics and Gynecology in a tertiary care hospital were selected for the study. Serum LH and FSH levels were determined and LH/FHS ratio (normal range ≤2) calculated in the study subjects. They underwent a detailed clinical, hormonal, and metabolic evaluation, which was performed between the second and third days of a natural or induced menstrual period. Results: Elevated LH/FSH ratio was found in 60 women (70.58%). Normal gonadotropin ratio was detected in 25 women (29.41%). Statistically significant differences in serum TSH levels were noted between groups with normal and elevated LH/FSH ratio. However, no statistically significant difference was noted in other endocrine parameters. Further analysis revealed a slight negative correlation of TSH with prolactin in the study subjects of PCOS with an ‘r’ value of − 0.3. Conclusions: LH/FSH ratio is one of the characteristic attribute of PCOS women. In the present study, this abnormality was detected in 70% of patients. Hypothyroidism was a common endocrinal abnormality and prolactin was inversely correlated to TSH levels in PCOS patients.
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Affiliation(s)
- Chandan K Nath
- Department of Biochemistry, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
| | - Bhupen Barman
- Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
| | - Ananya Das
- Department of Obstetrics and Gynaecology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
| | - Purnima Rajkhowa
- Department of Microbiology, Silchar Medical College, Assam, India
| | - Polina Baruah
- Department of Biochemistry, NIAEH, Shillong-18, Meghalaya, India
| | - Mriganka Baruah
- Department of Biochemistry, ESIC Medical College, Joka, Kolkata, West Bengal, India
| | - Arup Baruah
- Department of Surgery, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India
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27
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Torchen LC. Early phenotypes in polycystic ovary syndrome: some answers, more questions. Fertil Steril 2019; 111:266-267. [PMID: 30691628 DOI: 10.1016/j.fertnstert.2018.11.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 11/16/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Laura C Torchen
- Division of Endocrinology, Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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28
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Papadakis G, Kandaraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E. Polycystic Ovary Syndrome and NC-CAH: Distinct Characteristics and Common Findings. A Systematic Review. Front Endocrinol (Lausanne) 2019; 10:388. [PMID: 31275245 PMCID: PMC6593353 DOI: 10.3389/fendo.2019.00388] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 05/30/2019] [Indexed: 12/18/2022] Open
Abstract
Background: Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. Methods: The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were "polycystic ovary syndrome," "PCOS," "non-classical adrenal hyperplasia," "NC-CAH," "21-hydroxylase deficiency." From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. Results: The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. Conclusions: The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.
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Affiliation(s)
| | - Eleni A. Kandaraki
- Department of Endocrinology and Diabetes, HYGEIA Hospital, Athens, Greece
| | - Ermioni Tseniklidi
- Department of Endocrinology and Diabetes, HYGEIA Hospital, Athens, Greece
| | - Olga Papalou
- Department of Endocrinology and Diabetes, HYGEIA Hospital, Athens, Greece
| | - Evanthia Diamanti-Kandarakis
- Department of Endocrinology and Diabetes, HYGEIA Hospital, Athens, Greece
- *Correspondence: Evanthia Diamanti-Kandarakis
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29
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Arslanian S, Bacha F, Grey M, Marcus MD, White NH, Zeitler P. Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by the American Diabetes Association. Diabetes Care 2018; 41:2648-2668. [PMID: 30425094 PMCID: PMC7732108 DOI: 10.2337/dci18-0052] [Citation(s) in RCA: 216] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Silva Arslanian
- Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, University of Pittsburgh, Pittsburgh, PA
- Center for Pediatric Research in Obesity and Metabolism, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Fida Bacha
- Children's Nutrition Research Center, Texas Children's Hospital and Baylor College of Medicine, Houston, TX
| | - Margaret Grey
- Yale School of Nursing, New Haven, CT
- Yale School of Medicine, New Haven, CT
| | | | - Neil H White
- Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Philip Zeitler
- Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO
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30
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Hepşen S, Karaköse M, Çakal E, Öztekin S, Ünsal İ, Akhanlı P, Uçan B, Özbek M. The assessment of thyroid autoantibody levels in euthyroid patients with polycystic ovary syndrome. J Turk Ger Gynecol Assoc 2018; 19:215-219. [PMID: 29699958 PMCID: PMC6250086 DOI: 10.4274/jtgga.2018.0001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective: Thyroid hormone abnormalities are commonly seen in polycystic ovary syndrome (PCOS) and have considerable effects on comorbidities. The association with PCOS and thyroid autoimmunity which lead to thyroid pathologies are not revealed clearly. We targeted to commentate anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) antibody levels and thyroid autoimmunity in PCOS. Material and Methods: One hundred eighty four patients who got the diagnosis of PCOS regard to the revised 2003 Rotterdam criteria were embodied in this study. One hundred six age-matched female volunteers were included in the control group. Characteristics, biochemical parameters, thyroid hormone and autoantibody levels of groups were investigated. Results: Although; we did not find out a statistically significant difference in TSH and sT4 levels between two groups (p>0.05), anti-TPO and anti-TG antibody levels were determined higher in PCOS group significantly (p<0.001). Anti-TPO Ab and anti-TG Ab positivity prevalence of PCOS patients were significantly higher as against to controls (p<0.001; p=0.01). Conclusion: Not only thyroid hormone levels but also thyroid autoantibody levels should be screened during the investigation of PCOS and the patients with positive results need to be followed up carefully in the long run.
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Affiliation(s)
- Sema Hepşen
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Melia Karaköse
- Clinic of Endocrinology and Metabolism, Sivas Numune Hospital, Sivas, Turkey
| | - Erman Çakal
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Sanem Öztekin
- Clinic of Internal Medicine, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - İlknur Ünsal
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Pınar Akhanlı
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Bekir Uçan
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Mustafa Özbek
- Clinic of Endocrinology and Metabolism, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
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31
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Panagiotopoulos C, Hadjiyannakis S, Henderson M. Type 2 Diabetes in Children and Adolescents. Can J Diabetes 2018; 42 Suppl 1:S247-S254. [DOI: 10.1016/j.jcjd.2017.10.037] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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32
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Connolly A, Leblanc S, Baillargeon JP. Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome. Int J Endocrinol 2018; 2018:4315413. [PMID: 29971102 PMCID: PMC6008888 DOI: 10.1155/2018/4315413] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 05/03/2018] [Indexed: 12/15/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of androgen-secreting tissues to NEFA and/or defective NEFA metabolism, leading to lipotoxic effects. Indeed, lipotoxicity could trigger androgenic hyperresponsiveness to insulin, LH, and ACTH. In most PCOS women, lipotoxicity also causes insulin resistance, inducing compensatory hyperinsulinemia, and may thus further increase hyperandrogenemia. Many approaches aimed at insulin sensitization also reduce lipotoxicity and have been shown to treat PCOS hyperandrogenemia. Furthermore, our group and others found that angiotensin II type 2 receptor (AT2R) activation is able to improve lipotoxicity. We provided evidence, using C21/M24, that AT2R activation improves adipocytes' size and insulin sensitivity in an insulin-resistant rat model, as well as androgen levels in a PCOS obese rat model. Taken together, these findings point toward the important role of lipotoxicity in PCOS development and of the RAS system as a new target for the treatment of PCOS.
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Affiliation(s)
- Alexandre Connolly
- Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
| | - Samuel Leblanc
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
| | - Jean-Patrice Baillargeon
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, 3001 12e Avenue Nord, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
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33
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Anwar S, Shikalgar N. Prevention of type 2 diabetes mellitus in polycystic ovary syndrome: A review. Diabetes Metab Syndr 2017; 11 Suppl 2:S913-S917. [PMID: 28711517 DOI: 10.1016/j.dsx.2017.07.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Accepted: 07/01/2017] [Indexed: 01/28/2023]
Abstract
Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrinopathies in women of reproductive age, associated with metabolic sequelae which includes increased risk factors for impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). The adverse effects of DM2 affects a woman throughout her lifespan. Health care expenditure of DM2 highlights the need for prevention through appropriate screening, diagnosis and intervention. Lifestyle modification (LSM) programs that include diet and/or physical activity are suggested for patients characterized as prediabetic to delay the onset of adult DM2. Diet (i.e. low carbohydrate), combination of aerobic and resistance exercise with high intensity interval training (HIT) 150 to 175min/week with resistance exercise 2 to 3days/week and weight loss may be valuable supporters in the fight against IR, IGT and DM2 associated with PCOS.
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Affiliation(s)
- Safa Anwar
- Department of Physical Therapy, College of Applied Medical Sciences, Buraydah Private Colleges, Qassim, Saudi Arabia.
| | - Nigar Shikalgar
- Department of Physical Therapy, College of Applied Medical Sciences, Buraydah Private Colleges, Qassim, Saudi Arabia
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Abstract
PURPOSE OF REVIEW Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. RECENT FINDINGS Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.
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Affiliation(s)
- Laura C Torchen
- Division of Endocrinology, Ann & Robert H Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Box 54, Chicago, IL, 60611, USA.
- Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
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Brockmann PE, Koren D, Kheirandish-Gozal L, Gozal D. Gender dimorphism in pediatric OSA: Is it for real? Respir Physiol Neurobiol 2017; 245:83-88. [DOI: 10.1016/j.resp.2016.11.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 11/19/2016] [Accepted: 11/20/2016] [Indexed: 10/20/2022]
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Abstract
Controversy continues about the underlying etiopathogenesis, diagnostic criteria, and recommendations for polycystic ovary syndrome (PCOS) in adolescents. Recent literature has recognized these deficiencies and evidence based expert recommendations have become more available. The purpose of this chapter is to offer primary care providers a practical understanding and approach to the diagnosis and treatment of PCOS in adolescents. Although the presence of polycystic ovary morphology (PCOM) is included as a key diagnostic criterion of PCOS in adults, it is currently not recommended for the diagnosis in adolescents. As such, the diagnosis of PCOS in adolescents currently hinges on evidence of ovulatory dysfunction and androgen excess. Recommended evidence of ovulatory dysfunction includes: consecutive menstrual intervals >90 days even in the first year after menstrual onset; menstrual intervals persistently <21 or >45 days 2 or more years after menarche; and lack of menses by 15 years or 2-3 years after breast budding. Recommended evidence of androgen excess include: moderate to severe hirsutism; persistent acne unresponsive to topical therapy; and persistent elevation of serum total and/or free testosterone level. Importantly, a definitive diagnosis of PCOS is not needed to initiate treatment. Treatment may decrease risk of future comorbidity even in the absence of a definitive diagnosis. Deferring diagnosis, while providing symptom treatment and regular/ frequent follow-up of symptomology, is a recommended option. The treatment options for PCOS should be individualized to the presentation, needs, and preferences of each patient. Goals of treatment are to improve quality of life and long-term health outcomes. Lifestyle modifications remain first-line management of overweight and obese adolescents with PCOS. Combined oral contraceptives (COC) are first line pharmacotherapy for management of menstrual irregularity and acne, and metformin is superior to COCs for weight reduction and improved dysglycemia. COCs and metformin have similar effects on hirsutism, but often need to be paired with other treatment modalities to achieve further improvement of cutaneous symptoms. Clinicians should be cognizant that PCOS is associated with significant metabolic and psychological comorbidity and screen for these issues appropriately.
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Affiliation(s)
- Manmohan K Kamboj
- Section of Endocrinology, Department of Pediatrics, Nationwide Children's Hospital, the Ohio State University College of Medicine, Columbus, OH, USA
| | - Andrea E Bonny
- Section of Endocrinology, Department of Pediatrics, Nationwide Children's Hospital, the Ohio State University College of Medicine, Columbus, OH, USA.,Section of Adolecent Medicine, Department of Pediatrics, Nationwide Children's Hospital, the Ohio State University College of Medicine, Columbus, OH, USA
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Comparison of the effect between pioglitazone and metformin in treating patients with PCOS:a meta-analysis. Arch Gynecol Obstet 2017; 296:661-677. [PMID: 28770353 PMCID: PMC5591817 DOI: 10.1007/s00404-017-4480-z] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 07/25/2017] [Indexed: 12/11/2022]
Abstract
Background Pioglitazone was used to treat patients of PCOS in many researches, but the treatment has not been recognized by public or recommended by all the guidelines. Method We conducted a meta-analysis of the related literatures to objectively evaluate the clinical effectiveness and safety by comparing pioglitazone with metformin administrated by PCOS patients. Searches were performed in Cochrane Library, EMBASE and PubMed (last updated December 2016). Results Eleven studies among 486 related articles were identified through searches. Fixed effects and random effects models were used to calculate the overall risk estimates. The results of the meta-analysis suggest that improvement of the menstrual cycle and ovulation in pioglitazone treatment group was better than metformin group [OR = 2.31, 95% CI (1.37, 3.91), P < 0.001, I2 = 41.8%]. Improvement of the F-G scores in metformin treatment group was better than pioglitazone group [SMD = 0.29, 95% CI (0.0, 0.59), P = 0.048, I2 = 0.0%]. BMI was more elevated in pioglitazone group than in metformin group [SMD = 0.83, 95% CI (0.24, 1.41), P = 0.006, I2 = 82.8%]. There were no significant differences of the other data between the two groups. Conclusions This meta-analysis indicated that pioglitazone ameliorated menstrual cycle and ovulation better than metformin and metformin ameliorated BMI and F-G scores better than pioglitazone in treating patients with PCOS. Pioglitazone might be a good choice for the patients with PCOS who were intolerant or invalid to metformin for the treatment.
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Cree-Green M, Rahat H, Newcomer BR, Bergman BC, Brown MS, Coe GV, Newnes L, Garcia-Reyes Y, Bacon S, Thurston JE, Pyle L, Scherzinger A, Nadeau KJ. Insulin Resistance, Hyperinsulinemia, and Mitochondria Dysfunction in Nonobese Girls With Polycystic Ovarian Syndrome. J Endocr Soc 2017; 1:931-944. [PMID: 29264544 PMCID: PMC5686696 DOI: 10.1210/js.2017-00192] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 05/26/2017] [Indexed: 01/28/2023] Open
Abstract
Objective: Obese girls with polycystic ovarian syndrome (PCOS) have decreased insulin sensitivity (IS), muscle mitochondrial dysfunction and increased liver fat, which may contribute to their increased risk for type 2 diabetes. Less is known regarding normal-weight girls with PCOS. Methods: Normal-weight girls with PCOS [n =18, age 15.9 ± 1.8 years, body mass index (BMI) percentile 68 ± 18] and normal-weight controls (NWC; n = 20; age 15.0 ± 2.1 years, BMI percentile 60 ± 21) were studied. Tissue-specific IS was assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers and a 2-hour oral glucose tolerance test (OGTT). Hepatic fat was determined using magnetic resonance imaging. Postexercise muscle mitochondrial function was assessed with 31P MR spectroscopy. Results: Both groups had similar demographics, anthropomorphics, physical attributes, habitual physical activity levels and fasting laboratory values, except for increased total testosterone and DHEAS in PCOS. Clamp-assessed peripheral IS was lower in PCOS (10.4 ± 2.4 mg/kg/min vs 12.7 ± 2.1; P = 0.024). The 120-minute OGTT insulin and glucose concentrations were higher in PCOS (114 IU/mL ± 26 vs 41 ± 25, P = <0.001 and 119 ± 22 mg/dL vs 85 ± 23, P = 0.01, respectively). Muscle mitochondrial ADP and phosphocreatine time constants were slower in PCOS. Despite a higher percentage liver fat in PCOS, hepatic IS was similar between groups, as was adipose IS. Conclusions: Normal-weight girls with PCOS have decreased peripheral IS and muscle mitochondrial dysfunction, abnormal glucose disposal, relative postprandial hyperinsulinemia, and increased hepatic fat compared to NWC. Despite a normal BMI, multiple aspects of metabolism appear altered in normal-weight girls with PCOS.
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Affiliation(s)
- Melanie Cree-Green
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.,Center for Women's Health Research, Aurora, Colorado 80045
| | - Haseeb Rahat
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Bradley R Newcomer
- Deptartment of Physics, James Madison University, Harrisburg, Virginia 22807
| | - Bryan C Bergman
- Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Mark S Brown
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Gregory V Coe
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Lindsey Newnes
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Yesenia Garcia-Reyes
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Samantha Bacon
- Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Jessica E Thurston
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045
| | - Laura Pyle
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045.,Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Ann Scherzinger
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Kristen J Nadeau
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.,Center for Women's Health Research, Aurora, Colorado 80045
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Vuguin P, Sopher AB, Roumimper H, Chin V, Silfen M, McMahon DJ, Fennoy I, Oberfield SE. Alterations in Glucose Effectiveness and Insulin Dynamics: Polycystic Ovary Syndrome or Body Mass Index. Horm Res Paediatr 2017; 87:359-367. [PMID: 28478437 PMCID: PMC5914159 DOI: 10.1159/000471804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 03/17/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS To delineate the relationship of polycystic ovary syndrome (PCOS), obesity, and hyperandrogenism (HA) with glucose and insulin dynamics in adolescents across a broad body mass index (BMI). METHODS Seventy-four PCOS subjects (aged 16 years) and 82 controls (aged 16 years) were evaluated by an oral glucose tolerance test. Subjects were categorized by BMI: normal weight (21 ± 0.4), overweight/obesity (OO; 33 ± 1.0), and severe obesity (SO; 48 ± 1.4). Indices of glucose and insulin dynamics were determined. Multiple linear regression analysis was used to evaluate the contribution of PCOS, HA, and BMI to these indices. RESULTS BMI was significantly associated with systolic and diastolic blood pressure and insulin resistance. A significant interaction between BMI and PCOS and indices of post-glucose load was observed. The mean difference in peak glucose, early glucose response, area under the curve for glucose, and glucose effectiveness (SgIo) between PCOS and control subjects was significantly different between OO and SO. In PCOS subjects, testosterone was positively associated with BMI, fasting insulin, early insulin response, and diastolic blood pressure, and negatively associated with SgIo. CONCLUSIONS Abnormal glucose dynamics in adolescents with PCOS is mainly due to SO. The combination of PCOS and SO has a synergistic effect on glucose dynamics when compared to all other groups.
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Affiliation(s)
- Patricia Vuguin
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Aviva B. Sopher
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Hailey Roumimper
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Vivian Chin
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Miriam Silfen
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Donald J. McMahon
- Division of Endocrinology, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York Presbyterian/Columbia University Medical Center, New York, New York 10032
| | - Ilene Fennoy
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
| | - Sharon E. Oberfield
- Division of Pediatric Endocrinology, Children’s Hospital of New York-Presbyterian, Columbia University College of Physicians and Surgeons, New York, New York 10032
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Gynecologic and Obstetric Consequences of Obesity in Adolescent Girls. J Pediatr Adolesc Gynecol 2017; 30:156-168. [PMID: 26915924 DOI: 10.1016/j.jpag.2016.02.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 02/06/2016] [Accepted: 02/15/2016] [Indexed: 12/24/2022]
Abstract
In the past few decades, there has been an overwhelming increase in childhood and adolescent obesity worldwide. Besides the well recognized cardiometabolic complications and other physical conditions associated with obesity, during adolescence, it causes psychological and social distress in a period of life that is already sensitive for a girl. This in turn increases their risk of low self-esteem and depression. Furthermore, obesity diminishes health-related quality of life and years of life. Overweight and obese teenagers are more likely to have gynecologic and obstetric complications, during adolescence and also later in life. Consequences of obese and overweight childhood and adolescence include sexual maturation and reproductive dysfunction, alterations in menstruation, dysmenorrhea, risky sexual behavior, and inefficient use of contraception, polycystic ovary syndrome, bone density abnormalities, macromastia, and an increased risk of breast and endometrial cancer. Obese adolescents are at greater risk of pregnancy and perinatal complications, such as preeclampsia, gestational hypertension and preeclampsia, gestational diabetes mellitus, primary cesarean delivery, and induction of labor, to mention a few. Evidence shows that infants born to obese teenagers are also more likely to have complications including preterm or post-term delivery, small-for-gestational age newborns, macrosomia, meconium aspiration, respiratory distress, and even stillbirth, among others. This comprehensive review focuses on the gynecological and obstetric consequences of obesity in adolescent girls.
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Temur M, Yılmaz Ö, Aksun S, Calan M, Özün Özbay P, Kumbasar S, Sever E. The relationship of urocortin-2 with insulin resistance patients having PCOS. Gynecol Endocrinol 2017; 33:124-127. [PMID: 27841039 DOI: 10.1080/09513590.2016.1240772] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
In this study, we aimed to compare the serum urocortin-2 (UCN2) levels in women with polycystic ovary syndrome (PCOS) and healthy women. Thirty-eight patients with PCOS and 41 healthy women were included in the study whose age and BMI matched. The fasting serum glucose, insulin, free testosterone, hs-CRP and UCN2 levels of the all participants were examined. HOMA-IR formula was used in order to calculate the insulin resistance. Circulating UCN2 levels were significantly elevated in women with PCOS compared with controls (142.93 ± 59.48 versus 98.56 ± 65.01 pg/ml, p = 0.002). FBG, serum insulin, hs-CRP and HOMA-IR levels were found to be increased in women with PCOS. There was a positive correlation between UCN2 and free-testosterone in only PCOS group (r = 0.235, p = 0.027). Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.31 for patients in the highest quartile of UCN2 compared with those in the lowest quartile (OR = 2.31, 95% CI = 1.88-2.83, p=0.021). Multiple linear regression analysis revealed that HOMA-IR, hs-CRP and free-testosterone independently predicted UCN2 levels (p < 0.05). UCN2 levels were significantly higher in PCOS cases when compared to control group. UCN2 is thought to be effective on pathophysiology of PCOS by paracrine and autocrine pathways.
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Affiliation(s)
- Muzaffer Temur
- a Department of Obstetrics and Gynecology , Manisa Merkezefendi Hospital , Manisa , Turkey
- b Department of Obstetrics and Gynecology , Sakarya University Faculty of Medicine , Sakarya , Turkey
| | - Özgür Yılmaz
- c Manisa Merkezefendi State Hospital Department of Obstetrics and Gynecology , Manisa , Turkey
| | - Saliha Aksun
- d Department of Medical Biochemistry İzmir , İzmir Katipcelebi University Medical School , İzmir , Turkey
| | - Mehmet Calan
- e Department of Endocrinology İzmir , İzmir Bozyaka Education and Research Hospital , İzmir , Turkey
| | - Pelin Özün Özbay
- f Aydın Private Ege Liva Hospital Department of Obstetrics and Gynecology Aydın , Aydın , Turkey , and
| | - Serkan Kumbasar
- g Department of Obstetrics and Gynecology , Sakarya University School of Medicine, Sakarya Research and Education Hospital , Sakarya , Turkey
| | - Erman Sever
- g Department of Obstetrics and Gynecology , Sakarya University School of Medicine, Sakarya Research and Education Hospital , Sakarya , Turkey
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Glintborg D, Andersen M. MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome. Eur J Endocrinol 2017; 176:R53-R65. [PMID: 27601016 DOI: 10.1530/eje-16-0373] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 08/17/2016] [Accepted: 09/05/2016] [Indexed: 12/19/2022]
Abstract
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance. Available data from register-based and data linkage studies support that metabolic-vascular and thyroid diseases, asthma, migraine, depression and cancer are diagnosed more frequently in PCOS, whereas fracture risk is decreased. Drug prescriptions are significantly more common in PCOS than controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long-term morbidity could be worsened by obesity, sedentary way of life, Western-style diet and smoking, whereas lifestyle intervention including weight loss may partly or fully resolve the symptoms of PCOS and could improve the long-term prognosis. In this review, the possible implications of increased morbidity for the clinical and biochemical evaluation of patients with PCOS at diagnosis and follow-up is further discussed along with possible modifying effects of medical treatment.
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Affiliation(s)
- Dorte Glintborg
- Department of EndocrinologyOdense University Hospital, Odense C, Denmark
| | - Marianne Andersen
- Department of EndocrinologyOdense University Hospital, Odense C, Denmark
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Dhesi AS, Murtough KL, Lim JK, Schulkin J, McGovern PG, Power ML, Morelli SS. Metabolic screening in patients with polycystic ovary syndrome is largely underutilized among obstetrician-gynecologists. Am J Obstet Gynecol 2016; 215:579.e1-579.e5. [PMID: 27457114 DOI: 10.1016/j.ajog.2016.07.043] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 07/13/2016] [Accepted: 07/15/2016] [Indexed: 11/18/2022]
Abstract
Women with polycystic ovary syndrome have substantially higher rates of insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, and metabolic syndrome when compared with women without the disease. Given the high prevalence of these comorbidities, guidelines issued by the American College of Obstetricians and Gynecologists and the Endocrine Society recommend that all women with polycystic ovary syndrome undergo screening for impaired glucose tolerance and dyslipidemia with a 2 hour 75 g oral glucose tolerance test and fasting lipid profile upon diagnosis and also undergo repeat screening every 2-5 years and every 2 years, respectively. Although a hemoglobin A1C and/or fasting glucose are widely used screening tests for diabetes, both the American College of Obstetricians and Gynecologists and the Endocrine Society preferentially recommend the 2 hour oral glucose tolerance test in women with polycystic ovary syndrome as a superior indicator of impaired glucose tolerance/diabetes mellitus. However, we found that gynecologists underutilize current recommendations for metabolic screening in women with polycystic ovary syndrome. In an online survey study targeting American College of Obstetricians and Gynecologists fellows and junior fellows, 22.3% of respondents would not order any screening test at the initial visit for at least 50% of their patients with polycystic ovary syndrome. The most common tests used to screen for impaired glucose tolerance in women with polycystic ovary syndrome were hemoglobin A1C (51.0%) and fasting glucose (42.7%). Whereas 54.1% would order a fasting lipid profile in at least 50% of their polycystic ovary syndrome patients, only 7% of respondents order a 2 hour oral glucose tolerance test. We therefore call for increased efforts to encourage obstetrician-gynecologists to address metabolic abnormalities in their patients with polycystic ovary syndrome. Such efforts should include education of physicians early in their careers, at the medical student and resident level. Efforts should also include implementation of continuing medical education activities, both locally and at the national level, to improve understanding of the metabolic implications of polycystic ovary syndrome. Electronic medical record systems should be utilized to generate prompts for appropriate screening tests in patients with a diagnosis of polycystic ovary syndrome. Because obstetrician-gynecologists may be the only physicians seen by many polycystic ovary syndrome patients, particularly those in their young reproductive years, such interventions could effectively promote optimal preventative health care and early diagnosis of metabolic comorbidities in these at-risk women.
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Affiliation(s)
- Amy S Dhesi
- Rutgers-New Jersey Medical School, Newark, NJ.
| | - Katie L Murtough
- American College of Obstetricians and Gynecologists, Washington, DC
| | | | - Jay Schulkin
- American College of Obstetricians and Gynecologists, Washington, DC
| | | | - Michael L Power
- American College of Obstetricians and Gynecologists, Washington, DC
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Stempel H, Dodge A, Marriott E, Peterson AL. Referral Patterns and Cascade Screening for Familial Hypercholesterolemia in a Pediatric Lipid Clinic. J Pediatr 2016; 178:285-287. [PMID: 27592098 DOI: 10.1016/j.jpeds.2016.08.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 07/11/2016] [Accepted: 08/04/2016] [Indexed: 12/18/2022]
Abstract
Charts of 42 children with familial hypercholesterolemia from a dyslipidemia clinic were reviewed for initial cholesterol screen indication and cascade screening results. Indications were universal screening (8/28 after guideline release, none before), family history (26/42), risk factor (5/42), and other (3/42). Cascade screening identified 63 relatives with unknown familial hypercholesterolemia.
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Affiliation(s)
- Hilary Stempel
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ann Dodge
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Erin Marriott
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Amy L Peterson
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
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Cree-Green M, Bergman BC, Coe GV, Newnes L, Baumgartner AD, Bacon S, Sherzinger A, Pyle L, Nadeau KJ. Hepatic Steatosis is Common in Adolescents with Obesity and PCOS and Relates to De Novo Lipogenesis but not Insulin Resistance. Obesity (Silver Spring) 2016; 24:2399-2406. [PMID: 27804265 PMCID: PMC5117819 DOI: 10.1002/oby.21651] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 07/18/2016] [Accepted: 07/20/2016] [Indexed: 01/13/2023]
Abstract
OBJECTIVE Increased liver fat and type 2 diabetes are prevalent in women with polycystic ovarian syndrome (PCOS) and cause excess mortality, yet little is known about their development during adolescence. The objective of this study was to measure hepatic steatosis and related metabolic contributors in girls with obesity, with and without PCOS. METHODS Nondiabetic adolescents with obesity, 41 with PCOS (PCOS; age 15.0 [13.0-16.0] years, BMI 35.2 ± 0.61 kg/m2 ) and 30 without PCOS (OB; age 14.5 [13.0-17.0], BMI 33.2 ± 1.8), were studied. Visceral and liver fat were assessed with MRI. Serum measures included androgens and 16:1 and 18:1 N7 fatty acids specific to de novo lipogenesis. Adipose, hepatic, and peripheral insulin sensitivity (IS) were assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers. RESULTS Forty-nine percent of the PCOS group had hepatic steatosis versus fourteen percent of the OB group (P = 0.02), and the PCOS group had higher N7 (43 ± 4 vs. 29 ± 5 nmol/g; P = 0.02). Peripheral IS was lower in PCOS (9.4 [7.2-12.3] vs. 14.5 [13.1-18.05 mg/lean kg/min]; P < 0.001) as was hepatic (P = 0.006) and adipose IS (P = 0.005). Percent liver fat correlated with N7 (R = 0.46, P = 0.02) and visceral fat (R = 0.42, P < 0.001), not androgens or peripheral IS. CONCLUSIONS Nearly 50% of nondiabetic girls with PCOS and obesity have hepatic steatosis, which relates to visceral fat and lipogenesis, but not to IS or androgens.
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Affiliation(s)
- Melanie Cree-Green
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
- Department of Pediatric Endocrinology, Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
| | - Bryan C Bergman
- Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Gregory V Coe
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Lindsey Newnes
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Amy D Baumgartner
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Samantha Bacon
- Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Ann Sherzinger
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Laura Pyle
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
| | - Kristen J Nadeau
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Pediatric Endocrinology, Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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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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Chang AY, Oshiro J, Ayers C, Auchus RJ. Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the Dallas Heart Study. Clin Endocrinol (Oxf) 2016; 85:92-9. [PMID: 26608823 PMCID: PMC4882287 DOI: 10.1111/cen.12986] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 08/25/2015] [Accepted: 11/20/2015] [Indexed: 01/13/2023]
Abstract
OBJECTIVE Polycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events. DESIGN Cross-sectional analysis of data collected by the Dallas Heart Study, an urban, population-based cohort oversampled for blacks. PATIENTS A previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index. MEASUREMENTS Hormonal and clinical measures associated with PCOS and CV risk factors. RESULTS The study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and impaired fasting glucose (P < 0·05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P < 0·05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1·50 [95% CI, 1·03-2·30]; P = 0·04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women. CONCLUSIONS Race/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease.
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Affiliation(s)
- Alice Y Chang
- Division of Endocrinology, Metabolism, Diabetes and Nutrition, Mayo Clinic, Rochester, MN, USA
| | - June Oshiro
- Scientific Publications, Mayo Clinic, Rochester, MN, USA
| | - Colby Ayers
- Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Richard J Auchus
- Division of Metabolism, Diabetes, and Endocrinology, University of Michigan, Ann Arbor, MI, USA
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Wong JMW, Gallagher M, Gooding H, Feldman HA, Gordon CM, Ludwig DS, Ebbeling CB. A randomized pilot study of dietary treatments for polycystic ovary syndrome in adolescents. Pediatr Obes 2016; 11:210-20. [PMID: 26132306 PMCID: PMC4698106 DOI: 10.1111/ijpo.12047] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 05/07/2015] [Accepted: 05/08/2015] [Indexed: 01/20/2023]
Abstract
BACKGROUND Evidence is lacking to recommend one diet over another when treating polycystic ovary syndrome (PCOS). OBJECTIVES To obtain preliminary data, comparing the impact of a low-glycaemic load (LGL) vs. low-fat (LF) diet on biochemical hyperandrogenism in overweight and obese adolescents with PCOS. To ascertain feasibility of recruiting study participants, in partnership with an adolescent clinic, and implementing dietary interventions. METHODS Randomized controlled trial of 19 overweight and obese adolescents with PCOS and not using hormonal contraceptives (HCs). Interventions comprised nutrition education, dietary counselling and cooking workshops to foster adherence to a LGL (45% carbohydrate, 35% fat, 20% protein) or LF (55% carbohydrate, 25% fat, 20% protein) diet over 6 months. Serum bioavailable testosterone was the primary outcome. RESULTS Sixteen (LGL, n = 7; LF, n = 9) participants completed the study. Body fat percentage decreased (P < 0.05) in response to the interventions, with no difference between the LGL and LF groups (-1.2% vs. -2.2%; P = 0.16). Bioavailable testosterone did not change for either group (-0.4 vs. -1.8 ng dL(-1) ; P = 0.35). Regarding feasibility, recruiting adolescents posed a challenge, and use of HCs was a main reason for ineligibility. Participants attended 5.9 of 6 in-person visits and 2.6 of 3 cooking workshops, completed 4.9 of 6 telephone counselling calls, and reported high satisfaction with the diets and cooking workshops (≥8 on a 10-cm scale). CONCLUSIONS Dietary interventions were beneficial for weight control but did not attenuate biochemical hyperandrogenism. Innovative strategies are needed to recruit adolescents for studies aimed at assessing independent effects of diet on features of PCOS.
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Affiliation(s)
- Julia MW Wong
- New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, USA,Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada
| | - Melissa Gallagher
- New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, USA
| | - Holly Gooding
- Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital, Providence, RI, USA
| | - Henry A Feldman
- Clinical Research Center, Boston Children’s Hospital, Providence, RI, USA
| | - Catherine M Gordon
- Divisions of Adolescent Medicine and Endocrinology, Hasbro Children’s Hospital, Providence, RI, USA
| | - David S Ludwig
- New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, USA
| | - Cara B Ebbeling
- New Balance Foundation Obesity Prevention Center, Boston Children’s Hospital, Boston, MA, USA
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Al Khalifah RA, Florez ID, Dennis B, Thabane L, Bassilious E. Metformin or Oral Contraceptives for Adolescents With Polycystic Ovarian Syndrome: A Meta-analysis. Pediatrics 2016; 137:peds.2015-4089. [PMID: 27244814 DOI: 10.1542/peds.2015-4089] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/25/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Polycystic ovarian syndrome (PCOS) is a common disease. There is limited evidence to support various treatment choices. This leads to variable treatment practices. OBJECTIVES To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the use of metformin versus oral contraceptive pills (OCPs) for the treatment of PCOS in adolescents aged 11 to 19 years. DATA SOURCES We performed literature searches through Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials, and gray literature resources, up to January 29, 2015. STUDY SELECTION AND DATA EXTRACTION Two reviewers screened titles and abstracts of identified citations, assessed full text eligibility, and extracted information from eligible trials. RESULTS Four RCTs met the inclusion and exclusion criteria. The reviewed evidence came from 170 patients. Overall, OCP treatment resulted in modest improvement in menstrual cycle frequency (weighted mean difference [WMD] = 0.27, P < .01, 95% confidence interval [CI] -0.33 to -0.21) and mild reduction of acne scores (WMD = 0.3, P = .02, 95% CI 0.05 to 0.55). While metformin resulted in greater BMI reduction (WMD = -4.02, P < .01, 95% CI -5.23 to -2.81) it was associated with decreased dysglycemia prevalence (risk ratio: 0.41, P = .02, 95% CI 0.19 to 0.86) and improved total cholesterol and low-density lipoprotein levels. Metformin and OCPs were similar in terms of impact on hirsutism. CONCLUSIONS AND LIMITATIONS Current evidence is derived from very low to low quality evidence. Therefore, treatment choice should be guided by patient values and preferences while balancing potential side effects. Future high quality RCTs are needed to address several questions for the treatment of adolescents with PCOS.
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Affiliation(s)
- Reem A Al Khalifah
- Division of Endocrinology and Metabolism, Department of Pediatrics, Departments of Clinical Epidemiology and Biostatistics, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia;
| | - Ivan D Florez
- Departments of Clinical Epidemiology and Biostatistics, Department of Pediatrics, Universidad de Antioquia, Colombia; and
| | - Brittany Dennis
- Departments of Clinical Epidemiology and Biostatistics, St. George's University of London, Cranmer Terrace, London, United Kingdom
| | - Lehana Thabane
- Departments of Clinical Epidemiology and Biostatistics, Pediatrics and Anesthesia, McMaster University, Hamilton, Canada
| | - Ereny Bassilious
- Division of Endocrinology and Metabolism, Department of Pediatrics
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Faubert J, Battista MC, Baillargeon JP. PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Insulin action and lipotoxicity in the development of polycystic ovary syndrome: A review1. J Anim Sci 2016; 94:1803-11. [DOI: 10.2527/jas.2015-0089] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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