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Ranathunga I, Athukorala TG, Sumanatilleke MR, Somasundaram NP. Evaluation of socio-demographic and clinical characteristics of PCOS patients attending a tertiary care institute in Colombo. BMC Endocr Disord 2022; 22:289. [PMID: 36411444 PMCID: PMC9677619 DOI: 10.1186/s12902-022-01206-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 11/09/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous aetiology. It is characterized by irregular menses and or oligo/anovulation, hyper-androgenism, and polycystic ovaries. The prevalence and diagnosis of PCOS changes depending on which clinical criteria are utilized to confirm the diagnosis. The prevalence can be high as 8-13% when the Rotterdam criteria are used. However, there is significant inter-individual variation in presentation. We have studied the socio-demographic and clinical characteristics of PCOS patients attending the Endocrinology clinic in a tertiary care institute in Sri Lanka. METHODS A descriptive cross sectional study was conducted from September 2019 to September 2020 at the Endocrinology Unit of the National Hospital of Sri Lanka. All the patients who met the inclusion and exclusion criteria and who has a diagnosis of PCOS made according to Rotterdam criteria were recruited in to the study. After obtaining informed written consent, the data was collected using an interviewer administered questionnaire. HOMA-IR was calculated using the fasting insulin and blood glucose level. RESULTS The study enrolled sixty females. The mean age was 26.7 years (range 18-44). The mean weight was 64.8 (SD = 11.9) kg and BMI was 27.1 (SD = 4.8) kg/m-2. According to Asian BMI cut-offs, 1 (1.7%) patient was underweight and 13 (21.7%) had normal weight. Forty six (76.7%) had their weight in the overweight or obese category. Fifty four (90.0%) patients had clinical or biochemical evidence of hyperandrogenism while 24 (40%) had polycystic ovaries on trans-abdominal ultrasound scan and 50 (83.3%) had irregular menstrual cycles. According to the body fat percentage assessed by the whole body DEXA scan 4.1% normal body fat, while 50.0% and 45.8% had overweight and obesity respectively. HOMA-IR detected 61.1% to have high insulin resistance. Out of the patients who had USS of the abdomen 27.5% had co-existent non-alcoholic fatty liver. Fifty four percent of the patients had sub/infertility. CONCLUSIONS The majority of the population were overweight or obese and had higher prevalence of insulin resistance and non-alcoholic fatty liver. Out of the clinical characteristics used to make the diagnosis of PCOS, the presence of clinical or biochemical evidence of hyperandrogenism and irregular menstrual cycles are more common than the detection of polycystic ovaries on trans-vaginal USS. The higher prevalence of overweight, obesity, insulin resistance and NAFLD associated with PCOS makes the diagnosis and management of the disease crucial to prevent long term consequences of the disease.
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Affiliation(s)
- I Ranathunga
- Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo 10, Sri Lanka.
| | - T G Athukorala
- Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo 10, Sri Lanka
| | - M R Sumanatilleke
- Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo 10, Sri Lanka
| | - N P Somasundaram
- Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo 10, Sri Lanka
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Abstract
STUDY QUESTION Is the presence of polycystic ovary syndrome (PCOS) associated with more adverse infant outcomes in mothers with different types of diabetes? SUMMARY ANSWER The presence of PCOS implies higher risks of total (medically indicated and spontaneously combined) and spontaneous preterm birth in mothers with non-insulin-treated type 2 diabetes and gestational diabetes mellitus (GDM), and lower risk of offspring being large for gestational age (LGA) in mothers with insulin-treated diabetes. WHAT IS KNOWN ALREADY PCOS is suggested to be an independent risk factor for adverse infant outcomes, and it is highly prevalent in mothers with diabetes. However, the impact of PCOS on the associations of different types of maternal diabetes with preterm birth and offspring birth sizes has not been reported. STUDY DESIGN, SIZE, DURATION This is a population-based cohort study including all live births between 1996 and 2014 in Finland. Children with concurrent maternal diagnoses that could cause signs and symptoms similar to PCOS were excluded. A total of 1 097 753 children were included. PARTICIPANTS/MATERIALS, SETTING, METHODS National registries were linked to identify births with maternal PCOS (n = 24 682), stratified by diabetes types. Logistic regression was used to examine the association of maternal PCOS and comorbid insulin-treated diabetes, non-insulin-treated type 2 diabetes or GDM with offspring LGA and small for gestational age (SGA). Generalized estimating equation was used to assess the risk of preterm birth in relation to maternal PCOS and diabetes. Potential interaction between PCOS and diabetes was evaluated on both additive and multiplicative scales. MAIN RESULTS AND THE ROLE OF CHANCE Using mothers with no PCOS and no diabetes as the reference and adjusting for maternal and birth factors, there were higher risks of total (odds ratio (OR) 2.84, 95% CI 2.21 − 3.66 vs. OR 1.91, 95% CI 1.77 − 2.07, P = 0.01) and spontaneous (OR 4.02, 95% CI 2.94 − 5.50 vs. OR 2.35, 95% CI 2.13 − 2.59, P = 0.001) preterm birth for those with PCOS in mothers with non-insulin-treated type 2 diabetes and higher risks of total (OR 1.42, 95% CI 1.27–1.58 vs. OR 0.89, 95% CI 0.86–0.91, P = 0.0001) and spontaneous (OR 1.80, 95% CI 1.59–2.05 vs. OR 1.01, 95% CI 0.98–1.05, P = 0.0001) preterm birth for those with PCOS in mothers with GDM. Among mothers with type 2 diabetes, further adjusting for maternal BMI eliminated the difference in preterm birth risks between those with and those without PCOS, and adjustment for infertility treatment and pre-eclampsia also reduced the preterm risks associated with PCOS significantly. For mothers with GDM, however, the risks of total and spontaneous preterm birth remained higher for those with PCOS following these aforementioned adjustments or stratified analysis. The risk of offspring being LGA was lower for those with PCOS than those without PCOS among mothers with insulin-treated diabetes (OR 18.90, 95% CI 14.21–25.14 vs. OR 32.04, 95% CI 29.79–34.46, P = 0.0001), showing departure from additivity (relative excess risk due to interaction −11.74, 95% CI −16.17 to −7.31, P < 0.001) and multiplicativity (P < 0.001). PCOS did not alter the risk estimate of preterm birth in mothers with insulin-treated diabetes or offspring LGA and SGA in mothers with type 2 diabetes or GDM. LIMITATIONS, REASONS FOR CAUTION The register-based diagnoses used in this study captured only women with PCOS seeking medical care and having live births. Including female infertility associated with anovulation as PCOS exposure was a risk for misclassification. Sample sizes for pregestational diabetes were small. Insulin purchase during pregnancy in those without a diabetes diagnosis was not accounted for in the analysis. For patients treated with insulin or other medications, we were unable to assess how they complied with such prescriptions. Also, maternal BMI was recorded only once in early pregnancy, thus the potential influence of gestational weight gain on birth outcomes could not be examined. Data on the causes for preterm birth were not available from the registers. WIDER IMPLICATIONS OF THE FINDINGS The presence of PCOS implied higher risks of total and spontaneous preterm birth in mothers with type 2 diabetes or GDM, and lower risk of offspring being LGA in mothers with insulin-treated diabetes. The higher risks of preterm birth added by PCOS could be explained by prepregnancy BMI or in part by infertility treatment and pre-eclampsia in maternal non-insulin-treated type 2 diabetes, but not in maternal GDM. The differential effects of PCOS on the associations of different types of maternal diabetes with infant outcomes have implications for preventative strategies and clinical counseling for affected pregnancies. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Shandong Provincial Natural Science Foundation, China (ZR2020MH064 to X.C.), Shandong Province Medical and Health Technology Development Plan (2018WS338 to X.C.), the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C. and C.L.), the Finnish National Institute for Health and Welfare: Drug and pregnancy project (M.G.), the Swedish Research Council (2014-10171 to C.L.), the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council (SLL20170292 and SLL20190589 to C.L.), the Swedish Brain Foundation (FO2019-0201 and FO2020-0305 to C.L.). X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Xinxia Chen
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Mika Gissler
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
- Department of Information Services, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Catharina Lavebratt
- Correspondence address. Translational Psychiatry Unit, Centre for Molecular Medicine, Karolinska University Hospital, L8:00, 171 76 Stockholm, Sweden. Tel:+46-8-51776524; Fax:+46-8-51773909; E-mail:
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Long C, Feng H, Duan W, Chen X, Zhao Y, Lan Y, Yue R. Prevalence of polycystic ovary syndrome in patients with type 2 diabetes: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2022; 13:980405. [PMID: 36120432 PMCID: PMC9471325 DOI: 10.3389/fendo.2022.980405] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
PURPOSE With type 2 diabetes mellitus (T2DM) occurring at a younger age, a greater number of women with T2DM experience reproductive health problems. The prevalence of polycystic ovary syndrome (PCOS), a common reproductive disease associated with T2DM, remains unknown in women with T2DM. This systematic review and meta-analysis aimed to determine the prevalence of PCOS in women with T2DM. METHODS Stata 15.1 was used to perform a meta-analysis on the prevalence of PCOS in patients with T2DM included in this study. Additionally, a narrative review of the effects of different diagnostic methods, obesity, state, and other factors on the prevalence of PCOS was conducted. RESULTS Meta-analysis showed that the overall prevalence of PCOS in women with T2DM was approximately 21%. Subgroup analysis showed that the incidence of PCOS in female patients aged 25-45 years was higher than that in female patients aged < 25 years. The prevalence of PCOS in obese women was 14%, which was lower than that in normal weight women and normal weight or overweight or obese women. Women with T2DM in Oceania had the highest incidence of PCOS, followed by those in Europe and Asia; women with T2DM in North America had the lowest incidence. In terms of PCOS diagnostic standards, the prevalence of PCOS diagnosed by the National Institutes of Health was the lowest. The prevalence of PCOS diagnosed on the basis of clinical symptoms and biochemical characteristics was the highest, and the prevalence of PCOS diagnosed on the basis of medical records was 20%. CONCLUSIONS PCOS is a common disease in female patients with T2DM. The prevalence of PCOS in women with T2DM at childbearing age was higher than that in adolescent females. Women with T2DM at childbearing age should pay attention to the screening and prevention of PCOS to avoid the hazards of PCOS to reproductive health. SYSTEMATIC REVIEW REGISTRATION PROSPERO, identifier CRD42022318657.
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Affiliation(s)
- Caiyi Long
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haoyue Feng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen Duan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xin Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuemeng Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ying Lan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Rensong Yue, ; Ying Lan,
| | - Rensong Yue
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Rensong Yue, ; Ying Lan,
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Mattsson K, Nilsson-Condori E, Elmerstig E, Vassard D, Schmidt L, Ziebe S, Jöud A. Fertility outcomes in women with pre-existing type 2 diabetes-a prospective cohort study. Fertil Steril 2021; 116:505-513. [PMID: 34353572 DOI: 10.1016/j.fertnstert.2021.02.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 01/12/2021] [Accepted: 02/05/2021] [Indexed: 01/19/2023]
Abstract
OBJECTIVE To study childbirth and the risk of miscarriage and infertility among women who have received a diagnosis of type 2 diabetes before the start of their reproductive journey. DESIGN Register-based cohort study using the Skåne Healthcare Register SETTING: All healthcare visits for the whole population of the southernmost region in Sweden over the past 20 years PATIENT(S): All women who were aged 18-45 years between January 1, 1998 and December 31, 2019 and who received a clinical diagnosis of type 2 diabetes before their first childbirth, miscarriage, or infertility diagnosis (n = 230) were compared with a healthcare-seeking population of women without any type of diabetes, matched for calendar year and age (n = 179,434). INTERVENTION(S) None MAIN OUTCOME MEASURE(S): Childbirth, miscarriage, and infertility diagnosis RESULT(S): The birthrate was lower among women with type 2 diabetes (62.6% vs. 83.8%), and they were less likely to give birth (crude risk ratio [RR] = 0.73, 95% confidence interval [CI]: 0.66-0.81). They had a higher risk of experiencing a miscarriage (RR = 1.88, 95% CI: 1.50-2.36). The risk of infertility was increased (RR = 3.44, 95% CI: 2.88-4.10) as was the risk of having infertility and not giving birth (RR = 4.47, 95% CI: 3.44-5.82). All results remained the same after adjustment for polycystic ovary syndrome and obesity. CONCLUSION(S) Women with type 2 diabetes with onset before their reproductive journey were more often childless compared with women without diabetes and had a higher risk of experiencing both miscarriage and infertility. This patient group may be in need of targeted information regarding potential fertility issues as part of their clinical treatment.
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Affiliation(s)
- Kristina Mattsson
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden; Reproductive Medicine Center, Skåne University Hospital, Malmö, Sweden.
| | | | - Eva Elmerstig
- Center for Sexology and Sexuality Studies, Malmö University, Malmö, Sweden
| | - Ditte Vassard
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Lone Schmidt
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Søren Ziebe
- The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Anna Jöud
- Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden
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Nørgård BM, Catalini L, Jølving LR, Larsen MD, Friedman S, Fedder J. The Efficacy of Assisted Reproduction in Women with a Wide Spectrum of Chronic Diseases - A Review. Clin Epidemiol 2021; 13:477-500. [PMID: 34194244 PMCID: PMC8236837 DOI: 10.2147/clep.s310795] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/07/2021] [Indexed: 01/11/2023] Open
Abstract
Assisted reproductive technology (ART) treatments in women with underlying chronic diseases have become increasingly frequent. The objective of this review is to provide an overview of the literature examining the chance of having a live born child after ART in women with chronic diseases, compared to other women receiving ART. We focused on some of the most prevalent chronic diseases in women during their reproductive years, ie ulcerative colitis, Crohn's disease, rheumatoid arthritis, multiple sclerosis, epilepsy, hyperthyroidism, hypothyroidism, and diabetes mellitus. Secondly, we studied the chance of successful implantation. The literature search was performed in the database Pubmed.gov. including all studies published before October 2020. Title and abstracts of 58 papers were reviewed, 37 papers were excluded and other 8 studies were excluded after full-text evaluation. Only 13 papers were eligible for review. Results indicate that women with ulcerative colitis, Crohn's disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 might have problems with low implantation rate or early embryo development during ART. On the contrary, the few studies on women with hypothyroidism, diabetes mellitus type 1, and epilepsy suggest an equivalent chance of a live birth compared to other women undergoing ART. A possible explanation behind these differences could reside in the disease-specific dysregulation of the innate or adaptive immune system. To our knowledge, this is the first review on ART in women with chronic diseases, and it has disclosed that the evidence in this area is indeed sparse. We encourage others to examine live birth after ART in women with chronic diseases.
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Affiliation(s)
- Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Laura Catalini
- Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark
- Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Michael Due Larsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Center for Crohn’s and Colitis, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jens Fedder
- Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark
- Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Chung YK, Kim JJ, Hong MA, Hwang KR, Chae SJ, Yoon SH, Choi YM. Association Between Polycystic Ovary Syndrome and the Polymorphisms of Aryl Hydrocarbon Receptor Repressor, Glutathione-S-transferase T1, and Glutathione-S-transferase M1 Genes. Gynecol Endocrinol 2021; 37:558-561. [PMID: 33124502 DOI: 10.1080/09513590.2020.1832066] [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] [Indexed: 10/23/2022] Open
Abstract
OBJECTIVE To investigate the association between the aryl hydrocarbon receptor repressor (AhRR) C/G polymorphisms and glutathione-S-transferase M1 (GSTM1) and GSTT1 null mutation and the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS This was a case-control study of 478 women with PCOS and 376 aged-matched healthy controls. Genotyping of the AhRR C/G polymorphism and GSTM1 and GSTT1 were performed using real-time PCR analysis and multiplex PCR, respectively. RESULTS The genotype distribution of the AhRR C/G polymorphisms and GSTM1/GSTT1 null mutations did not differ between women with PCOS and controls. Using the wild-type combined AhRR CC and GSTT1 present genotype as a reference, the odds that a woman had PCOS were 1.54 (95% CIs 1.04-2.29) times higher if she had a combined AhRR CG or GG and GSTT1 null genotype. The odds that a woman had PCOS was 1.48 (95% CIs 1.08-2.04) times higher if she had a combined GSTM1/GSTT1 null genotype compared with the wild-type combined GSTM1/GSTT1 present genotype. However, there were no significant associations between the risk of PCOS and any combined AhRR and GSTM1. CONCLUSIONS Our data suggest that a combined AhRR CG or GG and GSTT1 null genotype or a combined GSTT1/GSTM1 null genotype might be associated with an increased risk of PCOS.
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Affiliation(s)
- Youn Kyung Chung
- Department of Obstetrics and Gynecology, National Cancer Center, Goyang, Korea
| | - Jin Ju Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - Min A Hong
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyu Ri Hwang
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
| | - Soo Jin Chae
- Department of Obstetrics and Gynecology, IORA Fertility Clinic, Suwon, Korea
| | - Sang Ho Yoon
- Department of Obstetrics and Gynecology, IORA Fertility Clinic, Suwon, Korea
| | - Young Min Choi
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
- The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
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Abstract
PCOS is a common and heterogeneous endocrine disorder in women of reproductive age, frequently associated with metabolic abnormalities. It was estimated that about 75% of these subjects have an impairment of insulin action, as measured by gold standard methods. While the relationship between insulin resistance and PCOS is consistently shown by a number of studies, the mechanisms underlying its primary origin still remains an unsolved issue. Insulin resistance and the associated hyperinsulinemia can induce both the endocrine and reproductive traits of PCOS. However, androgen excess, in turn, can impair insulin action, directly and/or through several changes occurring in different tissues. Body fat excess, which is another common feature in these women, can contribute to worsening the whole picture. Nevertheless, insulin resistance may also be found in many normal-weight individuals. Endocrine and metabolic abnormalities can develop in different moments, and probably there is fetal programming of these alterations. However, a number of vicious circles, with bidirectional relationships between androgen excess and insulin resistance, and with the contribution of several other factors, make it extremely difficult to understand where this process really originates. This review summarizes available evidence on this topic, in order to better understand the complex relationships linking hyperandrogenism and impaired insulin action in women with PCOS.
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Affiliation(s)
- P Moghetti
- Unit of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, P.le Stefani, 1, 37126, Verona, Italy.
| | - F Tosi
- Unit of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, P.le Stefani, 1, 37126, Verona, Italy
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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: 80] [Impact Index Per Article: 20.0] [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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Noroozzadeh M, Raoufy MR, Bidhendi Yarandi R, Faraji Shahrivar F, Moghimi N, Ramezani Tehrani F. Cardiac function and tolerance to ischemia/reperfusion injury in a rat model of polycystic ovary syndrome during the postmenopausal period. Life Sci 2020; 262:118394. [PMID: 32910953 DOI: 10.1016/j.lfs.2020.118394] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 08/28/2020] [Accepted: 09/02/2020] [Indexed: 12/21/2022]
Abstract
AIMS There is much controversy regarding whether cardiovascular events increase in women with polycystic ovary syndrome (PCOS) with aging. Considering the lack of possibility of certain investigations in humans, animal models of PCOS may be suitable resources to obtain the useful data needed. In this study; we aimed to investigate whether cardiac function and tolerance to ischemia/reperfusion (I/R) injury worsen in postmenopausal rats, who had PCOS at younger ages, compared to controls. MAIN METHODS The hearts of aged rats with a history of PCOS and their controls were isolated and perfused in a Langendorff apparatus. Values of hemodynamic parameters, including left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), rate pressure product (RPP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) were recorded using a power lab system. Blood serum levels of total testosterone (TT) and estradiol (E2) were determined by ELISA kits. Generalized Estimating Equation Model and t-student unpaired test results were used to compare the findings documented between two groups. KEY FINDINGS No statistically significant differences were observed in hemodynamic parameters of the heart including, LVSP, LVDP, RPP and ±dp/dt, between the rats of two groups of study, at baseline or before ischemia and after I/R. Nor were any significant differences observed in the levels of two hormones between the two groups (p > 0.05). SIGNIFICANCE History of PCOS during reproductive ages should not be considered an important risk factor for reduction in cardiac contractile function or less tolerance to I/R injury during the postmenopausal period.
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Affiliation(s)
- Mahsa Noroozzadeh
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Raoufy
- Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Razieh Bidhendi Yarandi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzaneh Faraji Shahrivar
- Department of Medical laboratory Sciences, Iranshahr University of Medical Sciences, Iranshahr, Iran
| | - Naghmeh Moghimi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Bednarska S, Fryczak J, Siejka A. Serum β-Klotho concentrations are increased in women with polycystic ovary syndrome. Cytokine 2020; 134:155188. [PMID: 32673996 DOI: 10.1016/j.cyto.2020.155188] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/24/2020] [Accepted: 06/26/2020] [Indexed: 12/12/2022]
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11
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Bogari NM. Genetic construction between polycystic ovarian syndrome and type 2 diabetes. Saudi J Biol Sci 2020; 27:2539-2543. [PMID: 32994709 PMCID: PMC7499096 DOI: 10.1016/j.sjbs.2020.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 04/30/2020] [Accepted: 05/03/2020] [Indexed: 12/01/2022] Open
Abstract
Polycystic ovarian syndrome (PCOS) in reproductive-aged women is identified to be one of the endocrine disorders. This heterogeneous disorder is categorized through oligo-anovulation and hyperandrogenemia. National institutes of health and Rotterdam criterions were used to diagnose PCOS women. Type 2 Diabetes (T2D) is one of the complications in PCOS which is connected through insulin resistance (IR), which is a condition in which liver, muscles and fat infrequently respond to the hormones, and this leads to extreme IR and consequently leads to T2D disease. PCOS is inherited by the autosomal dominant mode of inheritance and may also with the different intricate patterns. Till now, many studies have been performed in PCOS with the genes identified by T2D and till now no studies have shown the similar genetic association and pathophysiology between both the diseases. So, the current review aims to investigate the genetic relation between PCOS and T2D and why both the diseases cannot be reverted. In this review, published data were screened with the T2D related genes and single nucleotide polymorphisms in PCOS women. The case-control, hospital-based and meta-analysis molecular studies disclosed both positive and negative connotations. Genetically, no relationship has been established between PCOS and T2D. Maximum studies have shown as PCOS women had developed T2D later in life because as a risk-factor, but none of the studies documented T2D women having developed PCOS as a risk factor. Apart from this, the disease PCOS is developed in women with reproductive age and T2D develops in both the men and women during adulthood. This review concludes as there is a genetic relation only in between PCOS and T2D, but not with T2D to PCOS and further it cannot be explicitly reverted from T2D to PCOS.
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Affiliation(s)
- Neda M Bogari
- Faculty of Medicine, Department of Medical Genetics, Umm Al-Qura University, Saudi Arabia
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12
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Larsen MD, Jensen DM, Fedder J, Jølving LR, Nørgård BM. Live-born children after assisted reproduction in women with type 1 diabetes and type 2 diabetes: a nationwide cohort study. Diabetologia 2020; 63:1736-1744. [PMID: 32548699 PMCID: PMC7406522 DOI: 10.1007/s00125-020-05193-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 04/23/2020] [Indexed: 01/10/2023]
Abstract
AIMS/HYPOTHESIS Type 1 and type 2 diabetes are among the most prevalent chronic diseases in women in the fertile years and women with diabetes may experience several reproductive issues. We aimed to examine the chance of biochemical pregnancy, clinical pregnancy and live birth after assisted reproductive technology (ART) treatment in women with type 1 and type 2 diabetes and whether obesity per se influenced the results. METHODS This nationwide register-based cohort study is based on the Danish ART Registry comprising 594 women with either type 1 diabetes or type 2 diabetes from 2006 to 2017. RESULTS Relative to women without diabetes, the adjusted OR (95% CI) of a live birth per embryo transfer was 0.50 (0.36, 0.71) in women with type 2 diabetes and 1.10 (0.86, 1.41) in women with type 1 diabetes. CONCLUSIONS/INTERPRETATION Our data on the efficacy of ART treatment in women with type 1 and type 2 diabetes is the first in this field. When compared with women without diabetes, women with type 1 diabetes had an equivalent chance of a live birth per embryo transfer whereas women with type 2 diabetes had a reduced chance. The findings in women with type 2 diabetes did not seem to be driven by obesity per se as the same pattern was seen in both normal-weight and obese women. Graphical abstract.
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Affiliation(s)
- Michael Due Larsen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, Laboratoriesenteret, 5. etasje, 7491, Trondheim, Norway.
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.
| | - Dorte Møller Jensen
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
- Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Jens Fedder
- Department D, Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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13
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Thong EP, Codner E, Laven JSE, Teede H. Diabetes: a metabolic and reproductive disorder in women. Lancet Diabetes Endocrinol 2020; 8:134-149. [PMID: 31635966 DOI: 10.1016/s2213-8587(19)30345-6] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 08/27/2019] [Accepted: 09/03/2019] [Indexed: 02/07/2023]
Abstract
Reproductive dysfunction is a common but little studied complication of diabetes. The spectrum of reproductive health problems in diabetes is broad, and encompasses delayed puberty and menarche, menstrual cycle abnormalities, subfertility, adverse pregnancy outcomes, and potentially early menopause. Depending on the age at diagnosis of diabetes, reproductive problems can manifest early on in puberty, emerge later when fertility is desired, or occur during the climacteric period. Historically, women with type 1 diabetes have frequently had amenorrhoea and infertility, due to central hypogonadism. With the intensification of insulin therapy and improved metabolic control, these problems have declined, but do persist. Additional reproductive implications of contemporary diabetes management are now emerging, including polycystic ovary syndrome and hyperandrogenism, which are underpinned by insulin action on the ovary. The sharp rise in type 2 diabetes incidence in youth suggests that more women of reproductive age will encounter diabetes-related reproductive problems in their lifetimes. With an ever increasing number of young women living with diabetes, clinicians need to be aware of and equipped for the challenges of navigating reproductive health concerns across the lifespan.
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Affiliation(s)
- Eleanor P Thong
- Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia; Department of Endocrinology and Diabetes, Monash Health, Clayton, VIC, Australia
| | - Ethel Codner
- Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile
| | - Joop S E Laven
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Helena Teede
- Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia; Department of Endocrinology and Diabetes, Monash Health, Clayton, VIC, Australia.
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14
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Phan K, Charlton O, Smith SD. Hidradenitis suppurativa and polycystic ovarian syndrome: Systematic review and meta-analysis. Australas J Dermatol 2019; 61:e28-e33. [PMID: 31261440 DOI: 10.1111/ajd.13110] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/02/2019] [Indexed: 12/01/2022]
Abstract
BACKGROUND/OBJECTIVES Hidradenitis suppurativa has been associated with a number of pathologies, including various endocrine and autoimmune disorders. Although signs of hyperandrogenism are common in hidradenitis suppurativa, few formal studies have assessed the relationship between hidradenitis suppurativa and polycystic ovarian syndrome. Therefore, we performed a systematic review and meta-analysis to assess the association between hidradenitis suppurativa and polycystic ovarian syndrome. METHODS We performed a systematic review and meta-analysis according to PRISMA guidelines. Odds ratio was used as the effect size, with random-effects meta-analysis. RESULTS We identified five case-control studies for inclusion. From pooled data, we found a significantly higher proportion of polycystic ovarian syndrome in hidradenitis suppurativa cases compared with controls (OR 2.64; 95% CI 1.69-4.11; P < 0.00001). There was significant heterogeneity noted (I2 = 88%, P < 0.00001). Limitations included that studies reviewed were observational by design which are susceptible to bias, and lack of randomisation. CONCLUSIONS In summary, pooled analysis of existing case-control studies supports a significant association between hidradenitis suppurativa and polycystic ovarian syndrome. Our results imply that hidradenitis suppurativa patients with signs of hyperandrogenism may benefit from screening for polycystic ovarian syndrome, and may potentially benefit from anti-androgen therapy.
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Affiliation(s)
- Kevin Phan
- Department of Dermatology, Liverpool Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Olivia Charlton
- Department of Dermatology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Saxon D Smith
- Department of Dermatology, Royal North Shore Hospital, Sydney, New South Wales, Australia.,Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.,The Dermatology and Skin Cancer Centre, Sydney, New South Wales, Australia
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15
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Garg A, Neuren E, Strunk A. Hidradenitis Suppurativa Is Associated with Polycystic Ovary Syndrome: A Population-Based Analysis in the United States. J Invest Dermatol 2018; 138:1288-1292. [DOI: 10.1016/j.jid.2018.01.009] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 12/05/2017] [Accepted: 01/04/2018] [Indexed: 11/16/2022]
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Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. The aetiology of this syndrome remains largely unknown, but mounting evidence suggests that PCOS might be a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. The diagnosis and treatment of PCOS are not complicated, requiring only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches addressing hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders. This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS.
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Affiliation(s)
- Héctor F Escobar-Morreale
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
- Universidad de Alcalá, Alcalá de Henares, Spain
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
- Instituto Ramón y Cajal de Investigación Santiaria (IRYCIS), Madrid, Spain
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17
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Hormone-induced rat model of polycystic ovary syndrome: A systematic review. Life Sci 2017; 191:259-272. [DOI: 10.1016/j.lfs.2017.10.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 10/04/2017] [Accepted: 10/17/2017] [Indexed: 12/16/2022]
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18
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Huang WQ, Guo JH, Yuan C, Cui YG, Diao FY, Yu MK, Liu JY, Ruan YC, Chan HC. Abnormal CFTR Affects Glucagon Production by Islet α Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome. Front Physiol 2017; 8:835. [PMID: 29204121 PMCID: PMC5698272 DOI: 10.3389/fphys.2017.00835] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 10/09/2017] [Indexed: 12/26/2022] Open
Abstract
Glucagon, produced by islet α cells, functions to increase blood glucose. Abnormal glucose levels are often seen in cystic fibrosis (CF), a systematic disease caused by mutations of the CF transmembrane conductance regulator (CFTR), and in polycystic ovarian syndrome (PCOS), an endocrine disorder featured with hyperandrogenism affecting 5-10% women of reproductive age. Here, we explored the role of CFTR in glucagon production in α cells and its possible contribution to glucagon disturbance in CF and PCOS. We found elevated fasting glucagon levels in CFTR mutant (DF508) mice compared to the wildtypes. Glucagon and prohormone convertase 2 (PC2) were also upregulated in CFTR inhibitor-treated or DF508 islets, as compared to the controls or wildtypes, respectively. Dihydrotestosterone (DHT)-induced PCOS rats exhibited significantly lower fasting glucagon levels with higher CFTR expression in α cells compared to that of controls. Treatment of mouse islets or αTC1-9 cells with DHT enhanced CFTR expression and reduced the levels of glucagon and PC2. The inhibitory effect of DHT on glucagon production was blocked by CFTR inhibitors in mouse islets, and mimicked by overexpressing CFTR in αTC1-9 cells with reduced phosphorylation of the cAMP/Ca2+ response element binding protein (p-CREB), a key transcription factor for glucagon and PC2. These results revealed a previously undefined role of CFTR in suppressing glucagon production in α-cells, defects in which may contribute to glucose metabolic disorder seen in CF and PCOS.
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Affiliation(s)
- Wen Qing Huang
- Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Jing Hui Guo
- Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, Guangzhou, China
| | - Chun Yuan
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Yu Gui Cui
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Fei Yang Diao
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Mei Kuen Yu
- Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
| | - Jia Yin Liu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Ye Chun Ruan
- Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
| | - Hsiao Chang Chan
- Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
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19
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Braham R, Robert AA, Musallam MA, Alanazi A, Swedan NB, Al Dawish MA. Reproductive disturbances among Saudi adolescent girls and young women with type 1 diabetes mellitus. World J Diabetes 2017; 8:475-483. [PMID: 29204256 PMCID: PMC5700384 DOI: 10.4239/wjd.v8.i11.475] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 08/08/2017] [Accepted: 10/17/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To identify reproductive disturbances among adolescent girls and young women with type 1 diabetes mellitus (T1DM) in Saudi Arabia.
METHODS This cross sectional study was conducted among 102 female with T1DM, (aged 13-29 years) who attended the Diabetes Clinic at Diabetes Treatment Center, Prince Sultan Military Medical City, Saudi Arabia between April 2015 to March 2016. Clinical history, anthropometric characteristics and reproductive disturbance were collected through a questionnaire.
RESULTS Of 102 patients included in this analysis, 26.5% (27/102) were reported that they experienced an irregular menses. Of these patients, when compared to whose diabetes was diagnosed before menarche (35.4%, 17/48), patients diagnosed with diabetes after menarche (18.5%, 10/54) showed significantly less irregular menses (difference 16.9%, P = 0.04). Similarly, compared to patients diagnosed with diabetes prior to menarche (mean age 12.9 years; n = 48), patients diagnosed with diabetes after menarche (mean age 12.26 years; n = 54) were found to have 0.64 years delay in the age of menarche (P = 0.04). Among the studied patients, 15.7% (16/102) had polycystic ovary syndrome (PCOS). Of these PCOS patients, 37.5% (6/16) had irregular menses, 6.3% (1/16) had Celiac disease, 37.5% (6/16) had Hashimoto thyroiditis and 18.7% (3/16) had acne.
CONCLUSION More than one fourth of the study population with T1DM experiencing an irregular menses. Adolescent girls and young women diagnosed with diabetes prior to menarche showed higher menstrual irregularity and a delay in the age of menarche.
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Affiliation(s)
- Rim Braham
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Asirvatham Alwin Robert
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Maha Ali Musallam
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Abdulaziz Alanazi
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Nawaf Bin Swedan
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Mohamed Abdulaziz Al Dawish
- Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
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20
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Shaman AA, Mukhtar HB, Mirghani HO. Risk factors associated with metabolic syndrome and cardiovascular disease among women with polycystic ovary syndrome in Tabuk, Saudi Arabia. Electron Physician 2017; 9:5697-5704. [PMID: 29403608 PMCID: PMC5783117 DOI: 10.19082/5697] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 09/30/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder at a reproductive age. It is associated with a high risk of metabolic syndrome (MS) and cardiovascular diseases (CVD). OBJECTIVE To measure the prevalence of MS in women with PCOS and to assess the global cardiovascular risk (CVR) among them. METHODS This cross-sectional study was conducted at King Khalid Hospital, Tabuk, Saudi Arabia during the period from February through December 2014. A total of 404 infertile women were randomly selected, and checked for diagnosing PCOS, MS and estimated CVD probability. Data were analyzed by IBM-SPSS version 22, using independent-samples t-test, Chi-square, and conditional logistic regression. A p-value of <0.05 was considered significant. RESULTS MS was diagnosed in 58% and 32% of women with and without PCOS respectively (p<0.00). Results showed a statistically significant association between the two syndromes. Patients with the two syndromes showed high averages of clinical and biochemical values (p<0.00), high rate of predicted CVR, a high percentage of clustering of MS factors, and that weight-waist circumference - HDL are predictive for the occurrence of MS. CONCLUSION PCOS is associated with the risk of development of MS, and CVD. Screening for early detection of PCOS and MS and the application of cohort studies are recommended to better explore the role of PCOS in the development of CVD and to assess the significance of interventions.
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Affiliation(s)
- Amani Ali Shaman
- M.D., Assistant Professor in Obstetrics and Gynecology, Faculty of Medicine, University of Tabuk, Tabuk, Kingdom of Saudi Arabia
| | - Hytham Bahaeldin Mukhtar
- M.D., Assistant Professor in Obstetrics and Gynecology, Faculty of Medicine, University of Tabuk, Tabuk, Kingdom of Saudi Arabia
| | - Hyder Osman Mirghani
- M.D., Associate Professor in Internal Medicine and Endocrinology, Faculty of Medicine, University of Tabuk, Tabuk, Kingdom of Saudi Arabia
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21
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Reddy BM, Kommoju UJ, Dasgupta S, Rayabarapu P. Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India. Indian J Med Res 2017; 144:400-408. [PMID: 28139539 PMCID: PMC5320846 DOI: 10.4103/0971-5916.198678] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND & OBJECTIVES Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India. METHODS A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform. RESULTS None of the 15 SNPs were found to be significantly associated with PCOS after Bonferroni correction for multiple testing, either in the univariate or multivariate context. The cumulative effect of risk alleles observed with reference to T2DM was also not seen with reference to PCOS. INTERPRETATION & CONCLUSIONS The nine T2DM genes considered in this exploratory study might not be the primary susceptibility factors for PCOS among Indian women. Our results supplement the lack of evidence of the association of T2DM genes with PCOS among the Chinese and Caucasians hinting at the possible universality of this pattern. Specifically designed comprehensive studies that include women with T2DM and PCOS are required to explore the precise role of the diabetes genes.
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Affiliation(s)
- Battini Mohan Reddy
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Uma Jyothi Kommoju
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Shilpi Dasgupta
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Pranavchand Rayabarapu
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
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22
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Delitala AP, Capobianco G, Delitala G, Cherchi PL, Dessole S. Polycystic ovary syndrome, adipose tissue and metabolic syndrome. Arch Gynecol Obstet 2017. [DOI: 10.1007/s00404-017-4429-2] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Sortino MA, Salomone S, Carruba MO, Drago F. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols. Front Pharmacol 2017. [PMID: 28642705 PMCID: PMC5463048 DOI: 10.3389/fphar.2017.00341] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios.
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Affiliation(s)
- Maria A Sortino
- Pharmacology Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania UniversityCatania, Italy
| | - Salvatore Salomone
- Pharmacology Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania UniversityCatania, Italy
| | - Michele O Carruba
- Center for the Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of MilanMilan, Italy
| | - Filippo Drago
- Pharmacology Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, Catania UniversityCatania, Italy
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Ruan X, Kubba A, Aguilar A, Mueck AO. Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects. EUR J CONTRACEP REPR 2017; 22:183-190. [PMID: 28463030 DOI: 10.1080/13625187.2017.1317735] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 04/03/2017] [Accepted: 04/06/2017] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is a common, heterogeneous disorder characterised by hyperandrogenic skin symptoms, irregular menstruation and subfertility, increased risk of endometrial malignancy, and increased risk of preventable diseases associated with metabolic syndrome. Cyproterone acetate (CPA) 2 mg, combined with ethinylestradiol (EE) 35 μg, is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age. OBJECTIVES To review the present knowledge about PCOS and summarize the role of CPA/EE in the care of patients suffering from this condition for the practitioner. METHODS Experts with clinical interest and experience in treating symptoms of androgen excess performed a non-systematic review to provide updated information regarding the use of CPA/EE in patients with PCOS. RESULTS Polycystic ovary-related hyperandrogenic skin symptoms are effectively treated by CPA/EE, reducing not only the symptoms but also their negative impact on quality of life and mental health. Proven additional benefits for these patients include the treatment of menstrual irregularities and reduction in endometrial cancer risk. Possible benefits include preservation of fertility. Treatment increases the risk for venous thromboembolic complications. The nature of other metabolic and cardiovascular long-term effects i.e., whether positive or negative, are still to be investigated. CONCLUSIONS Cyproterone acetate/ethinylestradiol provides effective treatment for PCO-related hyperandrogenic skin symptoms. This efficacy and additional benefits related to menstrual irregularities and endometrial cancer risk, have to be weighed against the risk of venous thromboembolic complications based on an individual benefit/risk evaluation.
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Affiliation(s)
- X Ruan
- a Department of Gynecological Endocrinology , Beijing Obstetrics and Gynecology Hospital, Capital Medical University , Beijing , China
- b Department of Women's Health , University Women's Hospital and Research Centre of Women's Health, University Clinicum Centre of Tuebingen , Tuebingen , Germany
| | - A Kubba
- c Community Reproductive and Sexual Healthcare Unit , Guy's and St. Thomas' NHS Foundation Trust , London , UK
| | - A Aguilar
- d Department of Obstetrics and Gynecology , University of the Philippines College of Medicine, Center for Advanced Reproductive Medicine, St. Luke's Medical Center BGC , Manila , Philippines
| | - A O Mueck
- a Department of Gynecological Endocrinology , Beijing Obstetrics and Gynecology Hospital, Capital Medical University , Beijing , China
- b Department of Women's Health , University Women's Hospital and Research Centre of Women's Health, University Clinicum Centre of Tuebingen , Tuebingen , Germany
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Wellons MF, Matthews JJ, Kim C. Ovarian aging in women with diabetes: An overview. Maturitas 2016; 96:109-113. [PMID: 28041589 DOI: 10.1016/j.maturitas.2016.11.019] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 11/28/2016] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes is a global epidemic, and the prevalence and incidence of type 1 diabetes are increasing. The negative effects of diabetes on kidneys, nerves, and vessels are well established. The effect of diabetes on reproductive function is less well understood, but important to characterize, given the increasing numbers of young women with diabetes. In this review, we summarize the available literature on how women with diabetes experience ovarian aging, from menarche to menopause. We report that women with type 1 diabetes appear more likely to have ovarian dysfunction, manifested by delayed menses, menstrual irregularities, and possibly earlier menopause. Studies of women with type 2 diabetes are inconsistent but suggest increased anovulation and earlier menopause. Differences in reproductive aging between women with type 1 and type 2 diabetes raise questions about potential differences in the mechanisms contributing to ovarian aging. Although there is shared glycemic dysregulation, fundamental differences in insulin presence and processing distinguish the two diseases. This review suggests that insulin, age at diagnosis, and weight play a role in ovarian dysfunction. More long-term studies are needed to evaluate the multitude of factors that may disrupt hypothalamic, pituitary, and ovarian function in women with diabetes.
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Affiliation(s)
- Melissa F Wellons
- Vanderbilt University Medical Center, Department of Medicine, Nashville, Tenn. 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA.
| | - Juliana J Matthews
- Vanderbilt University Medical Center, Department of Medicine, Nashville, Tenn. 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA
| | - Catherine Kim
- University of Michigan, Department of Medicine, 2800 Plymouth Road, Building 16, Room 430W, Ann Arbor, MI 48109, USA
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Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev 2016; 37:467-520. [PMID: 27459230 PMCID: PMC5045492 DOI: 10.1210/er.2015-1104] [Citation(s) in RCA: 830] [Impact Index Per Article: 92.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 07/20/2016] [Indexed: 02/06/2023]
Abstract
Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.
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Affiliation(s)
- Robert L Rosenfield
- Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637
| | - David A Ehrmann
- Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637
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Noroozzadeh M, Tehrani FR, Mobarakabadi SS, Farahmand M, Dovom MR. Sexual function and hormonal profiles in women with and without polycystic ovary syndrome: a population-based study. Int J Impot Res 2016; 29:1-6. [PMID: 27654035 DOI: 10.1038/ijir.2016.35] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 04/30/2016] [Accepted: 06/18/2016] [Indexed: 01/23/2023]
Abstract
There is no consensus regarding the impact of polycystic ovary syndrome (PCOS) and its hormonal profile on sexual function of affected women; majority of data documented are not population based and there is a lack of studies investigating the association between hormonal profiles with sexual function in women with PCOS. We aimed to compare the sexual function of PCOS women with controls in a population-based study based on their hormonal profiles. In this cross-sectional study, sexual function (using the Female Sexual Function Index (FSFI) questionnaire) and hormonal profiles were determined in 63 PCOS subjects and 216 healthy women (controls); aged 18-45 years. A comparison of PCOS women and controls showed no statistically significant difference in total FSFI and each of its specific domain scores. There were significant positive correlations between dehydroepiandrosterone sulfate and total FSFI, orgasm and satisfaction domains in controls (r=0.156, r=0.206, r=0.275, respectively). No significant correlations between hormonal profiles and FSFI scores were found in the PCOS group, except for prolactin and orgasm (r=-0.250). In conclusion, sexual function did not differ between PCOS women and controls. High levels of androgens in women with PCOS were not associated with an improvement in sexual function.
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Affiliation(s)
- M Noroozzadeh
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - F Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - S Sedigh Mobarakabadi
- Department of Midwifery and Reproductive Health, Faculty of Nursing and Midwifery School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Farahmand
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Rostami Dovom
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sim SYT, Chin SL, Tan JLK, Brown SJ, Cussons AJ, Stuckey BGA. Polycystic ovary syndrome in type 2 diabetes: does it predict a more severe phenotype? Fertil Steril 2016; 106:1258-1263. [PMID: 27456547 DOI: 10.1016/j.fertnstert.2016.06.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 06/28/2016] [Accepted: 06/28/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS. DESIGN Cross-sectional study. SETTING Tertiary hospital. PATIENT(S) Female inpatients age 18-75 years with DM2. INTERVENTION(S) A face-to-face questionnaire was administered. MAIN OUTCOME MEASURE(S) Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. RESULT(S) One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m2 vs. 36.8 kg/m2), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). CONCLUSION(S) A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes.
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Affiliation(s)
- Stephanie Y T Sim
- School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia
| | - Sian L Chin
- School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia
| | - Jocelyn L K Tan
- Keogh Institute for Medical Research, Nedlands, Western Australia, Australia
| | - Suzanne J Brown
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Andrea J Cussons
- Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Bronwyn G A Stuckey
- School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Keogh Institute for Medical Research, Nedlands, Western Australia, Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
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Mayer SB, Evans WS, Nestler JE. Polycystic ovary syndrome and insulin: our understanding in the past, present and future. ACTA ACUST UNITED AC 2015; 11:137-49. [PMID: 25776288 DOI: 10.2217/whe.14.73] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and plays a critical pathophysiologic role in both the metabolic and reproductive complications of PCOS. This review focuses on the contribution of insulin resistance to anovulation in PCOS and to the high risk for Type 2 diabetes, metabolic syndrome and early cardiovasular disease. Key points for clinicians emphasized by this review are the following: PCOS is a clinical diagnosis and alternative diagnoses must be excluded; PCOS carries an inherent risk of insulin resistance and, hence, metabolic consequences for which women with PCOS should be screened regardless of BMI or degree of obesity; and PCOS is associated with infertility and this should be discussed early on in care of women diagnosed with PCOS, recognizing that there are several possible strategies to address infertility in women with PCOS, each with its own risks and benefits.
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Affiliation(s)
- Stéphanie B Mayer
- Division of Endocrinology & Metabolism, Virginia Commonwealth University, Richmond, VA, USA
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Hillson R. Diabetes, menstruation, and the uterus. PRACTICAL DIABETES 2015. [DOI: 10.1002/pdi.1981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Tavakolian Arjmand A, Nouri M, Tavakolian Arjmand S. Surprisingly low infertility rate in married type 2 diabetic women: A rather curious paradox to the current opinion of insulin resistance as the joint pathogenesis of poly cystic ovary syndrome and type 2 diabetes mellitus. Diabetes Metab Syndr 2015; 9:201-204. [PMID: 26364227 DOI: 10.1016/j.dsx.2015.08.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACK GROUND Sharing the same pathophysiologic principle which is insulin resistance, type 2 diabetes mellitus (T2DM) and poly cystic ovary syndrome (PCOS) are usually considered closely related and easily interchangeable medical entities. Numerous attempts have been made to document this illusory perspective. OBJECTIVE Based on a delicate pathophysiologic notion, we believe that fully developed T2DM is infrequently observed with fully featured PCOS. MATERIALS AND METHODS In an observational descriptive study 257 married T2DM women were consecutively included and meticulously investigated for fertility history and, albeit, clinical and biochemical features of PCOS. RESULTS Of 257 married diabetic women only six (2.3%) had no children. In one case a male problem (azoospermia) and in the second case, late marriage (aged 45 at wedding ceremony) was the cause of infertility. Thus, only four (1.6%) might have been labeled as true female factor infertility. Astounding to report was the average pregnancies for each participant which was 5.1±2.5, ranging from zero to fifteen. CONCLUSION we would suggest that, despite the well-established fact of insulin resistance as the common pathophysiologic process for T2DM and PCOS, they are definitely separate medical entities. As a matter of fact T2DM and PCOS are the two opposite aspect of the insulin resistance coin.
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Affiliation(s)
- Abbas Tavakolian Arjmand
- Reproductive Endocrinologist, Department of Internal Medicine, Shahrood Branch, Islamic Azad University, Shahrood, Iran
| | - Mahnaz Nouri
- Obstetrics and Gynecologist,Department Of Obstetrics & Gynecology, Sharood Branch, Islamic Azad University, Shahrood, Iran.
| | - Shima Tavakolian Arjmand
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
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Spritzer PM. Polycystic ovary syndrome: reviewing diagnosis and management of metabolic disturbances. ACTA ACUST UNITED AC 2015; 58:182-7. [PMID: 24830595 DOI: 10.1590/0004-2730000003051] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 11/26/2013] [Indexed: 12/18/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a common condition in women at reproductive age associated with reproductive and metabolic dysfunction. Proposed diagnosed criteria for PCOS include two out of three features: androgen excess, menstrual irregularity, and polycystic ovary appearance on ultrasound (PCO), after other causes of hyperandrogenism and dysovulation are excluded. Based on these diagnostic criteria, the most common phenotypes are the "classic PCOS"--hyperandrogenism and oligomenorrhea, with or without PCO; the "ovulatory phenotype"--hyperandrogenism and PCO in ovulatory women; and the "non-hyperandrogenic phenotype", in which there is oligomenorrhea and PCO, without overt hyperandrogenism. The presence of obesity may exacerbate the metabolic and reproductive disorders associated with the syndrome. In addition, PCOS women present higher risk for type 2 diabetes and higher prevalence of cardiovascular risk factors that seems to be associated with the classic phenotype. The main interventions to minimize cardiovascular and metabolic risks in PCOS are lifestyle changes, pharmacological therapy, and bariatric surgery. Treatment with metformin has been shown to improve insulin sensitivity, lowering blood glucose and androgen levels. These effects are more potent when combined with lifestyle interventions. In conclusion, besides reproductive abnormalities, PCOS has been associated to metabolic comorbidities, most of them linked to obesity. Confounders, such as the lack of standard diagnostic criteria, heterogeneity of the clinical presentation, and presence of obesity, make management of PCOS difficult. Therefore, the approach to metabolic abnormalities should be tailored to the risks and treatment goals of each individual woman.
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Affiliation(s)
- Poli Mara Spritzer
- Gynecologic Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre
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Ramos RB, Spritzer PM. FTO gene variants are not associated with polycystic ovary syndrome in women from Southern Brazil. Gene 2015; 560:25-9. [PMID: 25592819 DOI: 10.1016/j.gene.2015.01.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/01/2015] [Accepted: 01/05/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Polycystic ovary syndrome (PCOS) is a common endocrine disorder, presenting polygenic traits as well as determined by environmental factors. Given the overlap between PCOS and obesity, we assessed the frequencies of SNPs rs9939609 and rs8050136 in intron 1 of the FTO gene and their haplotypes in women with PCOS and healthy controls with regular cycles from Southern Brazil and investigated their relationship with metabolic traits and endocrine parameters. SUBJECTS AND METHODS The sample comprised 298 women (199 with PCOS and 99 non-hirsute women with regular ovulatory cycles). FTO genotyping was done by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using PHASE 2.1.1 software. RESULTS The distribution of rs9939609 (PCOS: 32.6% TT, 45.9% TA, 21.5% AA; controls: 33.3% TT, 49.0% TA, 17.7% AA) and rs8050136 (PCOS: 21.7% AA, 43.3% AC, 35.0% CC; controls: 14.9% AA, 48.9% AC, 36.2% CC) was similar between groups. The mean age of participants was 22.7±7.1years. Women with PCOS had significantly higher BMI, waist circumference, total testosterone, and FAI vs. controls. In the PCOS group, no differences between genotypes and haplotypes were found for clinical variables. The presence of at least one risk allele for polymorphisms rs9939609 and rs8050136 was associated with higher fasting glucose levels. CONCLUSION Our findings indicate that neither the FTO rs9939609 and rs8050136 polymorphisms nor its haplotypes are related to PCOS, but suggest an association between the presence of risk alleles of SNPs rs9939609 and rs8050136 in FTO and glucose levels in women from Southern Brazil.
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Affiliation(s)
- Ramon B Ramos
- Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-003, Brazil
| | - Poli Mara Spritzer
- Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-003, Brazil; Laboratory of Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-003, Brazil.
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Rondanelli M, Perna S, Faliva M, Monteferrario F, Repaci E, Allieri F. Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet 2014; 290:1079-92. [DOI: 10.1007/s00404-014-3433-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Accepted: 08/22/2014] [Indexed: 10/25/2022]
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Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013; 6:1-13. [PMID: 24379699 PMCID: PMC3872139 DOI: 10.2147/clep.s37559] [Citation(s) in RCA: 587] [Impact Index Per Article: 48.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.
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Affiliation(s)
- Susan M Sirmans
- Department of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA
| | - Kristen A Pate
- Department of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA
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Abstract
The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder affecting 4-7% of women, is often associated with metabolic alterations, chiefly insulin resistance and obesity. Based on available scientific evidence, PCOS should be regarded as an independent risk for the development of glucose intolerance states. This short review summarizes the available literature on the prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in this disorder. In addition, some insights on potential factors responsible for individual susceptibility are discussed. Targeted intervention studies focused on prevention and treatment of glucose intolerance states in PCOS are warranted.
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Affiliation(s)
- R Pasquali
- Division of Endocrinology, Department of Medical and Surgical Sciences (DIMEC), S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, Bologna, Italy.
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Dietary glycemic index is associated with less favorable anthropometric and metabolic profiles in polycystic ovary syndrome women with different phenotypes. Fertil Steril 2013; 100:1081-8. [PMID: 23830153 DOI: 10.1016/j.fertnstert.2013.06.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Revised: 06/03/2013] [Accepted: 06/03/2013] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To compare glycemic index (GI) in the usual diet of polycystic ovary syndrome (PCOS) and control women and to investigate whether dietary GI is associated with body composition and anthropometric and metabolic variables across PCOS phenotypes. DESIGN Cross-sectional study. SETTING University hospital outpatient clinic. PATIENT(S) Sixty-one women with PCOS and 44 nonhirsute women with ovulatory cycles. INTERVENTION(S) Metabolic work-up, biochemical and hormonal assays, assessment of body composition and rest metabolic rate, physical activity (pedometer), and food consumption (food frequency questionnaire). MAIN OUTCOME MEASURE(S) GI, glycemic load, dietary intake, and hormone and metabolic profile in PCOS versus control and in PCOS women stratified by tertiles of GI and PCOS phenotype. RESULT(S) Mean age was 23.7 ± 6.3 years. Participants with PCOS had higher body fat percentage, fasting insulin, insulin resistance, lipid accumulation product, and androgen levels compared with control women. PCOS and control women in the highest tertile of GI had higher body mass index and waist circumference than those in the lowest tertile. Dietary GI was higher in the classic PCOS group. Obesity and this more severe PCOS phenotype explained 28.3% of variance in dietary GI. CONCLUSION(S) Dietary GI is increased in the classic PCOS phenotype and associated with a less favorable anthropometric and metabolic profile. Obesity and classic PCOS phenotype are age-independent predictors of higher dietary GI.
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Al-Nozha O, Habib F, Mojaddidi M, El-Bab MF. Body weight reduction and metformin: Roles in polycystic ovary syndrome. ACTA ACUST UNITED AC 2013; 20:131-7. [PMID: 23608322 DOI: 10.1016/j.pathophys.2013.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2013] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Polycystic ovary syndrome (PCOS) is a common problem in women at fertile age. A prospective study was conducted to clarify the pathophysiological responses during an application of insulin sensitizer, metformin and weight reduction therapy at the Gynecology Center in Ohud hospital, in AL-Madinah AL-Munawarah, Kingdom of Saudi Arabia. METHODOLOGY Twenty healthy women served as controls and 180 PCOS women divided into three groups participated in the study. First group was treated with Clomid citrate 100mg/day from the 2nd day of menses to the 6th day plus gonadotrophin from day three to the 13th. Group II was treated as group I plus 850mg metformin twice a day and group III was treated as group I plus weight reduction. Clinical symptoms, menstrual pattern, hirsutism, blood glucose, body mass index, waist-to-hip ratio, insulin, hormonal, and lipid profiles were assessed pre- and post treatment. Insulin resistance was calculated. RESULTS PCOS women had significantly higher values than the healthy women in most of the measurements. Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR. Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels. HOMA-IR was significantly higher in women with PCOS. HOMA-IR was positively correlated with testosterone, estradiol, TG, total cholesterol and LDL-cholesterol parameters, and negatively correlated with HDL-cholesterol and FSH levels. CONCLUSION Metformin therapy and weight reduction had favorable influences on the basic metabolic and hormonal profiles in women with PCOS and that metformin and lifestyle modification (weight reduction via diet restriction or exercise) resulted in a significantly greater weight loss than hormonal therapy alone. Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.
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Affiliation(s)
- Omar Al-Nozha
- Department of Medicine, College of Medicine, Taibah University, P.O. Box 30001, AL-Madinah AL-Munawarah, Saudi Arabia.
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Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2012; 18:618-37. [PMID: 22767467 DOI: 10.1093/humupd/dms030] [Citation(s) in RCA: 555] [Impact Index Per Article: 42.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is closely associated with obesity but the prevalence of obesity varies between published studies. The objective of this research was to describe the prevalence of overweight, obesity and central obesity in women with and without PCOS and to assess the confounding effect of ethnicity, geographic regions and the diagnostic criteria of PCOS on the prevalence. METHODS MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting the prevalence of overweight, obesity or central obesity in women with and without PCOS. Data were presented as prevalence (%) and risk ratio (RR) [95% confidence interval (CI)]. Random-effect models were used to calculate pooled RR. RESULTS This systematic review included 106 studies while the meta-analysis included 35 studies (15129 women). Women with PCOS had increased prevalence of overweight [RR (95% CI): 1.95 (1.52, 2.50)], obesity [2.77 (1.88, 4.10)] and central obesity [1.73 (1.31, 2.30)] compared with women without PCOS. The Caucasian women with PCOS had a greater increase in obesity prevalence than the Asian women with PCOS compared with women without PCOS [10.79 (5.36, 21.70) versus 2.31 (1.33, 4.00), P < 0.001 between subgroups). CONCLUSIONS Women with PCOS had a greater risk of overweight, obesity and central obesity. Although our findings support a positive association between obesity and PCOS, our conclusions are limited by the significant heterogeneity between studies and further studies are now required to determine the source of this heterogeneity. Clinical management of PCOS should include the prevention and management of overweight and obesity.
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Affiliation(s)
- S S Lim
- The Robinson Institute, University of Adelaide, Adelaide, Australia
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Araki T, Elias R, Rosenwaks Z, Poretsky L. Achieving a successful pregnancy in women with polycystic ovary syndrome. Endocrinol Metab Clin North Am 2011; 40:865-94. [PMID: 22108285 DOI: 10.1016/j.ecl.2011.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a disease of complex and still poorly understood cause and of variable phenotypes. It is characterized by anovulation, hyperandrogenism, and polycystic ovaries. Infertility is commonly present. A variety of methods has been used successfully to achieve pregnancy in women with PCOS. Maintenance of pregnancy is complicated by a higher rate of premature spontaneous abortions and high risk of gestational diabetes, hypertension, and preeclampsia. However, with careful monitoring and treatment, the outcome of pregnancy in most women with PCOS is excellent.
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Affiliation(s)
- Takako Araki
- Division of Endocrinology and Metabolism, Beth Israel Medical Center and Albert Einstein College of Medicine, NY 10003, USA
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Tomlinson J, Millward A, Stenhouse E, Pinkney J. Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced? Diabet Med 2010; 27:498-515. [PMID: 20536945 DOI: 10.1111/j.1464-5491.2010.02994.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a risk factor for Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), but these risks are poorly defined. This study aimed to evaluate the evidence for these risks and whether screening and risk reduction are feasible. Medline reviews and data quality analysis were used using standard tools. Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin. However, no studies have determined whether T2DM incidence is reduced, (v) polycystic ovary syndrome is associated with cardiovascular disease (CVD) risk factors but data on CVD incidence are weak, (vi) risk factors for CVD are improved by the same interventions and statins and (vi) no studies have evaluated whether CVD incidence is reduced. While PCOS has important metabolic associations, and short-term interventions reduce risk factors for T2DM and CVD, data on prevalence and incidence of T2DM and particularly CVD are poor. There is a need for a clear definition of PCOS, for diabetes screening protocols and for long-term studies to determine whether risks can be reduced.
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Affiliation(s)
- J Tomlinson
- Peninsula College of Medicine and Dentistry, Research and Development, Knowledge Spa, Royal Cornwall Hospital, Cornwall, UK.
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Abstract
Obesity independently increases the risk of developing diabetes 10-fold compared with that for patients who are normal weight. Overweight patients with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) should be given counseling on weight loss of 5% to 10% of body weight as well as on increasing physical activity to at least 150 min/wk to prevent progression to diabetes. American Diabetes Association (ADA) recommends screening patients older than 45 years with a body mass index (BMI) greater than or equal to 25 for diabetes with fasting glucose every 3 years. Testing should be considered at a younger age or performed more frequently for those who are overweight and have 1 or more risk factors for diabetes.
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Affiliation(s)
- Richelle J Koopman
- Curtis W. and Ann H. Long Department of Family and Community Medicine, University of Missouri, Columbia, MO 65212, USA.
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Svendsen PF, Nilas L, Madsbad S, Holst JJ. Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin. Metabolism 2009; 58:586-93. [PMID: 19375579 DOI: 10.1016/j.metabol.2008.11.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2008] [Accepted: 11/06/2008] [Indexed: 10/20/2022]
Abstract
In normal subjects, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 70% of the insulin response during a meal; but in diabetic subjects and other insulin-resistant conditions, the incretin effect is impaired. Polycystic ovary syndrome (PCOS) is associated with insulin resistance, and the pathophysiologic mechanisms behind PCOS resemble those of type 2 diabetes mellitus; therefore, women with PCOS may have alterations in the incretin hormone response. Metformin is widely used in the treatment of both type 2 diabetes mellitus and PCOS. Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect. The objective of the study was to measure incretin hormone secretion in women with PCOS and to evaluate the effect of metformin treatment. Cross-sectional comparison of 40 women with PCOS (19 lean and 21 obese) and 26 healthy control women (9 lean and 17 obese) and longitudinal evaluation of the effects of 8 months of metformin 1000 mg twice daily in women with PCOS were performed. Plasma concentrations of GIP and GLP-1 were determined frequently during a 75-g glucose tolerance test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp. The incretin hormone response did not differ between subjects with and without PCOS. Subgroup analysis showed lower GIP (area under the curve [AUC]) levels in obese women with PCOS compared with obese control women (P < .05) and compared with lean women with PCOS (P < .05). Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07). The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.
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Affiliation(s)
- Pernille Fog Svendsen
- Department of Obstetrics and Gynaecology, Hvidovre Hospital, Hvidovre, 2650 Hvidovre, Denmark.
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Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2008; 91:456-88. [PMID: 18950759 DOI: 10.1016/j.fertnstert.2008.06.035] [Citation(s) in RCA: 1302] [Impact Index Per Article: 76.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2008] [Revised: 06/19/2008] [Accepted: 06/23/2008] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research. DESIGN Literature review and expert consensus. SETTING Professional society. PATIENTS None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. RESULT(S) The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence. CONCLUSION(S) Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.
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Affiliation(s)
- Ricardo Azziz
- Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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Abstract
While the treatment of bipolar disorder (BD) is typically complex, the treatment of women with bipolar disorder is even more challenging because clinicians must also individualize treatment based on the potential for pregnancy, drug interactions with oral contraceptives, and an increased risk of endocrine diseases that can either impact the course of illness or become manifest with some treatments. Women with BD should be checked for hypothyroidism, and if prescribed antidepressants, carefully watched for rapid cycling or a mood switch to mania, hypomania, or a mixed state. Several medications interact with oral contraceptives or increase the risk of developing polycystic ovary syndrome. Consideration of possible pregnancy is essential, and should be planned in advance whenever possible. Rates of recurrence have been shown to be equal in pregnant and nonpregnant women with BD. Risks of medication to the fetus at various points of development must be balanced against the risks of not treating, which is also detrimental to both fetus and mother. The postpartum period is a time of especially high risk; as many as 40% to 67% of women with BD report experiencing a postpartum mania or depression. The decision to breastfeed must also take into account the adverse impact of sleep deprivation in triggering mood episodes. In order to best address these issues, clinicians must be familiar with the data and collaborate with the patient to assess risks and benefits for the individual women and her family.
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Affiliation(s)
- Lauren B Marangell
- Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine Houston, Texas, USA.
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Amini M, Horri N, Farmani M, Haghighi S, Sattari G, Pornaghshband Z, Aminorroaya A. Prevalence of polycystic ovary syndrome in reproductive-aged women with type 2 diabetes. Gynecol Endocrinol 2008; 24:423-7. [PMID: 18850378 DOI: 10.1080/09513590802306143] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND Women with polycystic ovary syndrome (PCOS) are at higher risk of type 2 diabetes and cardiovascular disease. The present study was conducted to investigate the prevalence of PCOS in type 2 diabetic patients. METHODS Type 2 diabetic women (n = 157) of reproductive age were selected by a convenience sampling method. PCOS was confirmed using the clinical diagnosis criteria proposed in 1990 by the National Institute of Child Health and Human Development Conference of PCOS. The diabetic patients were divided into two groups according to the presence of PCOS. Baseline demographic characteristics were obtained by questionnaire, and body weight, height, waist circumference, blood pressure and some biochemical indices were measured in both groups. RESULTS The prevalence of PCOS was high (8.3%, 95% confidence interval 4.5-13.4%) in these type 2 diabetic women. The onset of diabetes occurred at a lower age in the PCOS group, who also displayed significantly greater waist circumference and body mass index (p<0.05). No difference in lipid profile, glycosylated hemoglobin or blood pressure was observed between the two groups. CONCLUSIONS PCOS is highly prevalent in type 2 diabetic patients. Hence, focusing the treatment on insulin sensitizers in these patients should improve both the metabolic and non-metabolic complications of PCOS.
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Affiliation(s)
- Massoud Amini
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Abstract
Polycystic ovarian syndrome (PCOS) is extremely common among reproductive-aged women, but often goes undiagnosed. PCOS is associated with the metabolic syndrome and carries a greatly increased risk of impaired glucose tolerance and type 2 diabetes mellitus, and cardiovascular risks. Treatment of PCOS may provide relief of cosmetic problems and depression by improving patient self-esteem. In addition, because of its association with the metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease, its recognition and treatment can potentially be life saving. This article reviews the impact, pathophysiology, and associated risks of obesity and the metabolic syndrome in PCOS.
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Escobar-Morreale HF, San Millán JL. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 2007; 18:266-72. [PMID: 17693095 DOI: 10.1016/j.tem.2007.07.003] [Citation(s) in RCA: 264] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2007] [Revised: 05/29/2007] [Accepted: 07/31/2007] [Indexed: 10/23/2022]
Abstract
Abdominal adiposity, overweightness and obesity are frequently present in patients with polycystic ovary syndrome (PCOS). A large body of evidence suggests that abdominal adiposity and the resulting insulin resistance contribute to ovarian and, possibly, adrenal hyperandrogenism. However, androgen excess itself might also contribute to abdominal fat deposition in hyperandrogenic women. Recent genomic and proteomic analyses of visceral fat from PCOS patients have detected differences in gene expression and protein content compared with those of non-hyperandrogenic women. Here we review the existing evidence for a vicious circle whereby androgen excess favoring the abdominal deposition of fat further facilitates androgen secretion by the ovaries and adrenals in PCOS patients.
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Affiliation(s)
- Héctor F Escobar-Morreale
- Department of Endocrinology, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, Carretera de Colmenar km 9'1, E-28034 Madrid, Spain.
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Talbott EO, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ. Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women. J Womens Health (Larchmt) 2007; 16:191-7. [PMID: 17388735 DOI: 10.1089/jwh.2006.0098] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Given the high prevalence of polycystic ovarian syndrome (PCOS) in the population, the increased risk for the development of type 2 diabetes in these women, and the role of type 2 diabetes in mediating adverse long-term sequelae, the objective of this analysis was to quantify the contribution of this early-life exposure (e.g., PCOS) to the burden of type 2 diabetes in the total population of middle-aged women. METHODS The cumulative incidence and relative risk (RR) of type 2 diabetes were examined in a group of women with PCOS (n = 149) and unaffected women (n = 166), aged 35-64, who were part of an ongoing investigation of cardiovascular risk factors in women with PCOS. The population attributable risk percent (PAR%) was calculated using Levin's formula to estimate the percentage of type 2 diabetes in the total population among middle-aged women that can be attributed to the presence of PCOS at young adulthood. RESULTS When the RR of type 2 diabetes among women with PCOS observed in our current study and others (4.0-6.0) was applied to an estimated 6%-10% prevalence of PCOS in the female population, 15.0%-35.6% of all incident cases of type 2 diabetes in white women were estimated to be attributable to PCOS. Moreover, other investigators have noted this proportion of undiagnosed PCOS in populations of women with type 2 diabetes. CONCLUSIONS These results support the recommendation that all women with PCOS should be periodically rescreened for diabetes and underscores the importance of the early identification of young women with PCOS and the need for early lifestyle intervention.
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Affiliation(s)
- Evelyn O Talbott
- Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA.
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50
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Abstract
Approximately one-third to one-half of all women and adolescent girls with polycystic ovary syndrome (PCOS) has the metabolic syndrome, associated with increased risk for cardiovascular disease and type 2 diabetes. Evidence suggests that insulin resistance is the likely link between PCOS and the metabolic syndrome. Early screening for impaired glucose tolerance, even in adolescents, is recommended. Lifestyle modification with increased physical activity and weight reduction remains first-line therapy. Insulin-sensitizing drugs may also ameliorate features of the metabolic syndrome in PCOS but long-term prospective studies are needed to determine the role of these drugs in the prevention of the metabolic syndrome.
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Affiliation(s)
- Paulina A Essah
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, USA.
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