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Mahabamunuge J, Sekula NM, Lepore C, Kudrimoti M, Upadhyay A, Alshowaikh K, Li HJ, Seifer DB, AlAshqar A. The Molecular Basis of Polycystic Ovary Syndrome and Its Cardiometabolic Correlates: Exploring the Intersection and Its Clinical Implications-A Narrative Review. Biomedicines 2025; 13:709. [PMID: 40149685 PMCID: PMC11940587 DOI: 10.3390/biomedicines13030709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/04/2025] [Accepted: 03/11/2025] [Indexed: 03/29/2025] Open
Abstract
Recent studies have highlighted the association between polycystic ovary syndrome (PCOS) and cardiometabolic diseases, leading to an improved understanding of the underlying mechanistic factors. PCOS significantly increases cardiovascular risk by predisposing individuals to various subclinical and clinical conditions, including atherosclerosis and type 2 diabetes mellitus. Additionally, it interacts synergistically with other traditional cardiovascular risk factors, such as obesity, hyperlipidemia, and insulin resistance. Several molecular mechanisms involving genetics, epigenetics, adipokine secretion, hyperandrogenemia, and hyperinsulinemia play a role in the relationship between PCOS and these comorbidities. For instance, androgen excess has been implicated in the development of hypertension, type 2 diabetes mellitus, endothelial dysfunction, and ultimately, broader cardiovascular disease. A deeper understanding of these underlying mechanisms facilitates the development of diagnostic, preventative, and therapeutic strategies directed at reducing cardiometabolic morbidity. This narrative review summarizes the current evidence, explores the potential clinical implications of these findings, and discusses emerging therapies to reduce cardiometabolic morbidity in women with PCOS.
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Affiliation(s)
- Jasmin Mahabamunuge
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Nicole M. Sekula
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Christina Lepore
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Meghana Kudrimoti
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Animesh Upadhyay
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Khadija Alshowaikh
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
| | - Howard J. Li
- Division of Reproductive Endocrinology and Infertility, National Institutes of Health, Bethesda, MD 20892, USA;
| | - David B. Seifer
- Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, New Haven, CT 06510, USA;
| | - Abdelrahman AlAshqar
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA; (J.M.); (N.M.S.); (C.L.); (M.K.); (A.U.); (K.A.)
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de Melo Cavalcante RB, Leão LMCSM, Tavares ABW, Lopes KG, Kraemer-Aguiar LG. Fat Distribution and its Correlation with Insulin Resistance, Androgen Markers, and Proinflammatory Cytokines in Polycystic Ovary Syndrome. Horm Metab Res 2025; 57:25-32. [PMID: 39226924 DOI: 10.1055/a-2386-9281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
The high cardiometabolic risk associated with polycystic ovary syndrome (PCOS) may be linked to central fat accumulation. This study compared fat distribution between women with PCOS and controls matched by body mass index. It also sought to determine if insulin resistance (IR), androgens, or inflammatory markers correlate with body composition parameters in PCOS patients. In total, thirty-five women with PCOS and 37 controls, aged 18-40 years, were included. Hormonal/metabolic profiles, inflammatory biomarkers [tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6)], anthropometry (waist circumference, waist-to-hip ratio, lipid accumulation product [LAP], visceral adiposity index [VAI]), and body composition assessed through dual-energy X-ray absorptiometry were assessed. The PCOS group exhibited significantly higher androgen levels and markers of IR. However, levels of TNF-α and IL-6 were comparable between the groups. Despite having similar total body fat mass (FM), the PCOS group had excessive central fat, including increased truncal FM and visceral adipose tissue (VAT). In PCOS, androgens were not associated with body fat or its distribution. IL-6 was positively correlated with total and truncal FM, while insulinemia and the homeostatic model assessment for IR were positively associated with VAT, as well as with total and truncal FM. Although anthropometric measurements and indices were positively associated with DXA-derived central FM parameters, our data suggest that LAP is the most effective tool for assessing central fat deposition and metabolic dysfunction in the PCOS patients studied herein. Furthermore, in this population, IR, rather than androgens or proinflammatory cytokines, is more closely associated with abdominal obesity.
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Affiliation(s)
- Rebeca Bandeira de Melo Cavalcante
- Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
| | | | - Ana Beatriz Winter Tavares
- Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
- Endocrinology Department of Internal Medicine, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
| | - Karynne Grutter Lopes
- Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
- Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Luiz Guilherme Kraemer-Aguiar
- Postgraduate Program in Clinical and Experimental Pathophysiology, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
- Endocrinology Department of Internal Medicine, Rio de Janeiro State University Faculty of Medical Sciences, Rio de Janeiro, Brazil
- Obesity Unit (SAI-Ob), Multiuser Clinical Research Center (CePeM), Pedro Ernesto University Hospital, Rio de Janeiro State University, Rio de Janeiro, Brazil
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Nandakumar M, Das P, Sathyapalan T, Butler AE, Atkin SL. A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D. Int J Mol Sci 2024; 25:6330. [PMID: 38928037 PMCID: PMC11204004 DOI: 10.3390/ijms25126330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 05/29/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D3 and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS (n = 29) and controls (n = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D3 (25(OH)D3) and the active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D3 and 1,25(OH)2D3 levels did not differ between groups. Nine CVRPs were higher in PCOS (p < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D3 correlated with five CVRPs in PCOS and one in controls (p < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D3, suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.
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Affiliation(s)
- Manjula Nandakumar
- Royal College of Surgeons of Ireland, Adliya P.O. Box 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Priya Das
- Royal College of Surgeons of Ireland, Adliya P.O. Box 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UK;
| | - Alexandra E. Butler
- Royal College of Surgeons of Ireland, Adliya P.O. Box 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
| | - Stephen L. Atkin
- Royal College of Surgeons of Ireland, Adliya P.O. Box 15503, Bahrain; (M.N.); (P.D.); (S.L.A.)
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Dubey P, Reddy S, Sharma K, Johnson S, Hardy G, Dwivedi AK. Polycystic Ovary Syndrome, Insulin Resistance, and Cardiovascular Disease. Curr Cardiol Rep 2024; 26:483-495. [PMID: 38568339 DOI: 10.1007/s11886-024-02050-5] [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] [Accepted: 03/20/2024] [Indexed: 06/26/2024]
Abstract
PURPOSE OF REVIEW Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events. RECENT FINDINGS IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.
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Affiliation(s)
- Pallavi Dubey
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, 79905, USA.
| | - Sireesha Reddy
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, 79905, USA
| | - Kunal Sharma
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, 79905, USA
| | - Sarah Johnson
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Ghislain Hardy
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, 79905, USA
| | - Alok Kumar Dwivedi
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
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van der Ham K, Koster MPH, Velthuis BK, Budde RPJ, Fauser BCJM, Laven JSE, Louwers YV. Change in Androgenic Status and Cardiometabolic Profile of Middle-Aged Women with Polycystic Ovary Syndrome. J Clin Med 2023; 12:5226. [PMID: 37629271 PMCID: PMC10455407 DOI: 10.3390/jcm12165226] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/01/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Understanding the cardiovascular disease (CVD) risk for women with polycystic ovary syndrome (PCOS) at reproductive age is crucial. To investigate this, we compared the cardiometabolic profiles of different PCOS groups over a median interval of 15.8 years. The study focused on three groups: (1) women with PCOS who were hyperandrogenic at both initial and follow-up screening (HA-HA), (2) those who transitioned from hyperandrogenic to normoandrogenic (HA-NA), and (3) those who remained normoandrogenic (NA-NA). At initial and follow-up screenings, both HA-HA and HA-NA groups showed higher body mass indexes compared to the NA-NA group. Additionally, at follow-up, the HA-HA and HA-NA groups exhibited higher blood pressure, a higher prevalence of hypertension, elevated serum triglycerides and insulin levels, and lower levels of HDL cholesterol compared to the NA-NA group. Even after adjusting for BMI, significant differences persisted in HDL cholesterol levels and hypertension prevalence among the groups (HA-HA: 53.8%, HA-NA: 53.1%, NA-NA: 14.3%, p < 0.01). However, calcium scores and the prevalence of coronary plaques on CT scans were similar across all groups. In conclusion, women with PCOS and hyperandrogenism during their reproductive years exhibited an unfavorable cardiometabolic profile during their post-reproductive years, even if they changed to a normoandrogenic status.
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Affiliation(s)
- Kim van der Ham
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands (J.S.E.L.)
| | - Maria P. H. Koster
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands (J.S.E.L.)
| | - Birgitta K. Velthuis
- Department of Radiology, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Ricardo P. J. Budde
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Bart C. J. M. Fauser
- Department of Reproductive Medicine & Gynecology, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Joop S. E. Laven
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands (J.S.E.L.)
| | - Yvonne V. Louwers
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands (J.S.E.L.)
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Nandakumar M, Sathyapalan T, Butler AE, Atkin SL. Oxidative Stress Markers and Heat Shock Proteins in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D. Biomedicines 2023; 11:2044. [PMID: 37509682 PMCID: PMC10377564 DOI: 10.3390/biomedicines11072044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/10/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
INTRODUCTION Oxidative stress (OS) is recognized in the pathophysiology of polycystic ovary syndrome (PCOS). OS results in intracellular reactive oxygen species generation, causing oxidative protein damage that is protected by heat shock proteins (HSPs). Vitamin D is thought to reduce and protect against OS; therefore, OS, HSP, and vitamin D levels may be associated with PCOS. However, their expression in PCOS without underlying inflammation is unknown. METHODS In this exploratory study, the plasma levels of 7 OS proteins and 10 HSPs that are affected by the OS process were measured using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurements in non-obese, non-insulin resistant women with PCOS (n = 24) without systemic inflammation and control (n = 24) women; the cohorts were matched for weight and age. The OS proteins and HSPs were correlated with 25-hydroxy vitamin D3 (25(OH)D3) and the active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), as measured by isotope-dilution liquid chromatography tandem mass spectrometry. RESULTS The PCOS women versus the controls had comparable insulin resistance and systemic inflammation (C-reactive protein 2.0 mg/L vs. 2.3 mg/L, p > 0.05), but higher free androgen index and anti-mullerian hormone levels. Among the OS proteins, only esterase D (ESD; p < 0.01) was elevated in PCOS and the HSPs did not differ between the PCOS and control women. There was no correlation of 25(OH)D3 or 1,25(OH)2D3 with any of the proteins. CONCLUSIONS In a PCOS population that was non-obese and without insulin resistance and systemic inflammation, only ESD was elevated in PCOS, whilst the other OS proteins and HSPs were not elevated. Further, none of the OS proteins or HSPs were correlated with either 25(OH)D3 or 1,25(OH)2D3 in either cohort of women or when both cohorts were combined, indicating that the OS and HSP responses were largely absent and not affected by vitamin D in a non-obese PCOS population.
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Affiliation(s)
- Manjula Nandakumar
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen, Adliya 15503, Bahrain
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RU, UK
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen, Adliya 15503, Bahrain
| | - Stephen L Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen, Adliya 15503, Bahrain
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Anala AD, Saifudeen ISH, Ibrahim M, Nanda M, Naaz N, Atkin SL. The Potential Utility of Tirzepatide for the Management of Polycystic Ovary Syndrome. J Clin Med 2023; 12:4575. [PMID: 37510690 PMCID: PMC10380206 DOI: 10.3390/jcm12144575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 06/27/2023] [Accepted: 07/02/2023] [Indexed: 07/30/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The metabolic dysfunction associated with PCOS increases the probability of developing type 2 diabetes (T2D), endometrial cancer, and cardiovascular disease. Research has shown that the metabolic features of PCOS may be improved by weight loss following treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists. Tirzepatide is a dual GLP-GIP (gastric inhibitory polypeptide) receptor agonist that shares a very similar mechanism of action with GLP-1R agonists, and it is hypothesized that it may be a potential contender in the treatment of PCOS. The success of GLP-1R agonists is usually hindered by their adverse gastrointestinal effects, leading to reduced compliance. The mechanism of action of Tirzepatide partly addresses this issue, as its dual receptor affinity may reduce the intensity of gastrointestinal symptoms. Tirzepatide has been licensed for the treatment of type 2 diabetes and given the metabolic issues and obesity that accompanies PCOS, it may be of value in its management for those PCOS patients who are obese with metabolic syndrome, although it may not benefit those who are of normal weight. This study reviews the current therapies for the treatment of PCOS and evaluates the potential use of Tirzepatide to address the symptoms of PCOS, including reproductive dysfunction, obesity, and insulin resistance.
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Affiliation(s)
- Alekya Devi Anala
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain
| | | | - Maryam Ibrahim
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain
| | - Moksha Nanda
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain
| | - Nida Naaz
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain
| | - Stephen L Atkin
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain
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Ke Y, Wu K, Liu S. Commentary: Cardiovascular risk according to body mass index in women of reproductive age with polycystic ovary syndrome: A systematic review and meta-analysis. Front Cardiovasc Med 2022; 9:920144. [PMID: 36035914 PMCID: PMC9399438 DOI: 10.3389/fcvm.2022.920144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 07/19/2022] [Indexed: 12/04/2022] Open
Affiliation(s)
- Yani Ke
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Kaihan Wu
- The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China
| | - Shan Liu
- Department of Clinical Evaluation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Shan Liu
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Guo F, Gong Z, Fernando T, Zhang L, Zhu X, Shi Y. The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population. Front Endocrinol (Lausanne) 2022; 13:892125. [PMID: 35860700 PMCID: PMC9289193 DOI: 10.3389/fendo.2022.892125] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/31/2022] [Indexed: 01/23/2023] Open
Abstract
Purpose To exhibit the lipid profiles in PCOS women with different characteristics and to access correlations between alternation of key lipid parameters and characteristics of PCOS. Design A retrospective study. Participants A total of 700 PCOS women were included. Methods Retrospective study on 700 women (age 24.6 ± 4.7 years), diagnosed with PCOS in the outpatient department of Obstetrics and Gynecology Hospital of Fudan University according to Rotterdam criteria. Anthropometric features, hormone levels, lipid levels, and metabolic parameters were measured and compared between PCOS patients with different characteristics. Results There was a high prevalence of dyslipidemia among Chinese PCOS patients (41.3%), and the most common pattern was low HDL. Patients with clinical hyperandrogenism presented with significantly decreased HDL and Apo-A levels. The levels of TG, LDL, Apo-B, TG/HDL, and Apo-B/Apo-A were significantly increased in the insulin resistance subgroup. The levels of TC and TG were significantly increased in the dysglycemia and T2DM women. And in general, the levels of TG, and Apo-B had an increasing trend with BMI. Moreover, AI, TG/HDL, and Apo-B/Apo-A ratios were associated with some characteristics of PCOS, such as insulin resistance, and obesity. Conclusion The PCOS women with different characteristics presented with different lipid profiles, and there is a complex correlation between lipid metabolism and PCOS characteristics, which may explain the increased risk of long-term cardiovascular disease. Regular screening of blood lipids is essential for PCOS women. Identification of optimal subgroups in PCOS patients that need lipid-lowering treatment and therapeutic effectiveness is worth exploring.
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Affiliation(s)
- Fei Guo
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
| | - Zhentao Gong
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
| | - Taniya Fernando
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
| | - Lingshan Zhang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Xiaoyong Zhu
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Yingli Shi
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
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Osibogun O, Ogunmoroti O, Kolade OB, Hays AG, Okunrintemi V, Minhas AS, Gulati M, Michos ED. A Systematic Review and Meta-Analysis of the Association Between Polycystic Ovary Syndrome and Coronary Artery Calcification. J Womens Health (Larchmt) 2022; 31:762-771. [PMID: 35575750 PMCID: PMC9360175 DOI: 10.1089/jwh.2021.0608] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: Polycystic ovary syndrome (PCOS) is a common endocrine pathology affecting women of reproductive age characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Coronary artery calcification (CAC) is a marker of subclinical atherosclerosis and prognostic of cardiovascular disease (CVD) risk. Some studies have shown that women with PCOS have a greater risk of CAC; however, a few others report contrary findings. The objective of this study is to examine and quantify the association between PCOS and CAC. Materials and Methods: We searched EMBASE, Google Scholar, PubMed, and Web of Science from inception to November 2021 to identify studies that provided information on PCOS and CAC. We used a random-effects model to aggregate the odds ratios (ORs) for CAC (score >0) among women with PCOS compared with controls adjusted for sociodemographic characteristics and CVD risk factors. Results: From the 36 articles reviewed, 3 prospective cohort and 4 cross-sectional studies met the inclusion criteria with a total of 2341 participants. Six studies used CAC > 0 as an outcome and were included in the pooled analysis. Using the Hartung-Knapp-Sidik-Jonkman method, the pooled adjusted ORs for the associations between PCOS and the presence of CAC were 2.48 (95% confidence interval: 2.11-2.84) with no significant heterogeneity (I2 = 0.10%, p = 0.97) for the cohort studies and 1.88 (0.71-3.06) with no significant heterogeneity (I2 = 13.95%, p = 0.87) for the cross-sectional studies. Conclusion: In pooled analyses, women with PCOS had approximately twofold greater odds of having CAC compared with women without PCOS. However, additional prospective studies will be needed to further understand the relationship between PCOS and CAC.
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Affiliation(s)
- Olatokunbo Osibogun
- Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Oluseye Ogunmoroti
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Olamide B. Kolade
- Department of Women's Health, Geisinger Lewistown Hospital, Lewistown, Pennsylvania, USA
| | - Allison G. Hays
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Victor Okunrintemi
- Division of Cardiovascular Disease, Houston Methodist Hospital, Houston, Texas, USA
| | - Anum S. Minhas
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Martha Gulati
- Division of Cardiology, University of Arizona, Phoenix, Arizona, USA
| | - Erin D. Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
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11
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Olaniyi KS, Areloegbe SE. Suppression of PCSK9/NF-kB-dependent pathways by acetate ameliorates cardiac inflammation in a rat model of polycystic ovarian syndrome. Life Sci 2022; 300:120560. [PMID: 35452635 DOI: 10.1016/j.lfs.2022.120560] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 12/14/2022]
Abstract
AIM Endocrinometabolic disorders in women of reproductive age, including polycystic ovarian syndrome (PCOS) has contributed to increased prevalence of cardiovascular disease (CVD) risk and its attendant complications. Acetate, the most abundant endogenously produced short chain fatty acid has been linked to metabolic health. However, the impact of acetate on CVD-driven pathologies in PCOS is unknown. The present study therefore investigated the effects of acetate on cardiometabolic abnormalities associated with PCOS in rat model, and the possible involvement of PCSK9/NF-kB-dependent pathways. MATERIALS AND METHODS Eight-week-old female Wistar rats were allotted into four groups (n = 6) and the groups received vehicle, acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole plus acetate respectively. The administrations were done once daily by oral gavage and lasted for 21 days. KEY FINDINGS In letrozole-induced PCOS rats characterized with insulin resistance, glucose dysregulation, elevated plasma testosterone and decreased 17-β estradiol as well as degenerated ovarian follicles, there was a significant increase in plasma and cardiac lipid/lipoproteins, lipid peroxidation, inflammatory mediators (NF-kB and TNF-α), γ-glutamyl transferase/lactate dehydrogenase and lactate content, PCSK9 and reduction in plasma and cardiac antioxidants (glutathione peroxidase and reduced glutathione) and plasma nitric oxide synthesis (eNOS and NO) compared with the control rats. In addition, immunohistochemical assessment of cardiac tissue showed severe expression of inflammasome in letrozole-induced PCOS rats compared with the control rats. Nevertheless, supplementation with acetate significantly attenuated these alterations. SIGNIFICANCE The present results suggest that acetate protects against cardiac inflammation in a rat model of PCOS by suppression of PCSK9 and NF-kB-dependent mechanisms.
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Affiliation(s)
- Kehinde S Olaniyi
- Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
| | - Stephanie E Areloegbe
- Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
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12
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Mahboobifard F, Rahmati M, Niknam A, Rojhani E, Momenan AA, Azizi F, Ramezani Tehrani F. Impact of Polycystic Ovary Syndrome on Silent Coronary Artery Disease and Cardiovascular Events; A Long-term Population-based Cohort Study. Arch Med Res 2022; 53:312-322. [PMID: 34823887 DOI: 10.1016/j.arcmed.2021.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 10/29/2021] [Accepted: 11/04/2021] [Indexed: 11/02/2022]
Abstract
BACKGROUND The existing data regarding the impact of Polycystic Ovary Syndrome (PCOS) on the risk of developing cardiovascular disease (CVD) are conflicting. AIM To explore the effect of PCOS status on the occurrence of silent coronary artery disease (CAD)/CVD. METHODS A total of 1591 women without CVD at baseline, aged 18-45 years, including 356 PCOS patients (defined by the Rotterdam criteria) and 1235 eumenorrheic non-hirsute women without polycystic ovarian morphology (controls), were selected from the Tehran Lipid and Glucose Study (TLGS). The median follow-up was 15.4 years, and most participants were in their late reproductive years at the end of the study. Silent CAD and CVD outcomes in PCOS and control groups were compared according to the multivariable-adjusted hazard ratios (HRs) and cumulative hazard functions. RESULTS There was no difference in CVD risk factors between the PCOS and control groups. After controlling for confounders, PCOS status did not increase the risk of silent CAD (HR: 0.96, 95% CI 0.86-1.08). Regardless of PCOS status, women with a history of silent CAD showed 2.25 times higher CVD events than those without this history (95% CI 1.63-3.10). PCOS status reduced the CVD incidence by 42%, independently of silent CAD or traditional risk factors (HR: 0.58, 95% CI 0.35-0.98). CONCLUSIONS Whereas silent CAD, regardless of PCOS, accelerated CVD, PCOS preserved it, most likely due to a combination of protective factors, including the endocrine pattern in the late reproductive period, environmental/social elements, and recruiting additional counseling and lifestyle modifications.
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Affiliation(s)
- Fatemeh Mahboobifard
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Rahmati
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atrin Niknam
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Rojhani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Abbas Momenan
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine 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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13
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Sun D, Wu Y, Ding M, Zhu F. Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome. Angiology 2022; 73:622-634. [PMID: 35258380 DOI: 10.1177/00033197211072598] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = -.649 (-.946, -.353), P < .001) and NMD (SMD (95% CI) = -.502 (-.686, -.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant (P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg' test or Egger's test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.
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Affiliation(s)
- Dandan Sun
- Department of Cardiovascular Ultrasound, 159408The People's Hospital of China Medical University and The People's Hospital of Liaoning Province, Shenyang, China
| | - Yupeng Wu
- Department of Neurosurgery, 159408The People's Hospital of China Medical University and The People's Hospital of Liaoning Province, Shenyang, China
| | - Mingyan Ding
- Department of Cardiovascular Ultrasound, 159408The People's Hospital of China Medical University and The People's Hospital of Liaoning Province, Shenyang, China
| | - Fang Zhu
- Department of Cardiovascular Ultrasound, 159408The People's Hospital of China Medical University and The People's Hospital of Liaoning Province, Shenyang, China
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14
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Zhuang C, Luo X, Wang W, Sun R, Qi M, Yu J. Cardiovascular Risk According to Body Mass Index in Women of Reproductive Age With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Front Cardiovasc Med 2022; 9:822079. [PMID: 35252398 PMCID: PMC8893173 DOI: 10.3389/fcvm.2022.822079] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 01/17/2022] [Indexed: 01/19/2023] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. The association between PCOS and cardiovascular risk according to body mass index (BMI) categories is unclear. Objective We evaluated the association between cardiovascular risk according to BMI categories and PCOS in women of reproductive age. Methods A literature search was conducted in the EMBASE, MEDLINE, Cochrane Library, and PubMed databases from their inception to 9 September, 2021. Observational cross-sectional, retrospective, and prospective controlled studies were included. The main analyses examined the relationship between cardiovascular risks (i.e., blood pressure and lipid levels) and BMI in women of reproductive age with PCOS. Results Thirty-eight studies, with a total of 6,078 subjects, were included in this metaanalysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in women of reproductive age with PCOS. Lower high-density lipoprotein (HDL)-cholesterol [SMD (95% CI): −0.21 (−0.35, −0.08), p = 0.002], higher triglycerides [SMD (95% CI): 0.38 (0.29, 0.48), p < 0.001], higher low-density lipoprotein (LDL)-cholesterol [SMD (95% CI): 0.29 (0.20, 0.39), p < 0.001], higher nonHDL-cholesterol [SMD (95% CI): 0.42 (0.31, 0.52), p < 0.001] and waist-to-hip ratio (WHR) [MD (95% CI): 0.03 (0.02, 0.04), p < 0.001] were seen in women of reproductive age with PCOS. In addition, the subgroup analysis revealed that systolic BP and HDL-cholesterol increased at BMI < 25 kg/m2 and BMI 25–30 kg/m2. Diastolic BP increased at BMI 25–30 kg/m2. Triglycerides, LDL-cholesterol, nonHDL-cholesterol, and WHR increased in all BMI categories. Conclusions PCOS is associated with cardiovascular risk. Lipid levels and BP increased in women of reproductive age with PCOS, regardless of BMI. Systematic Review Registration Open Science Framework (10.17605/OSF.IO/92NBY).
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Affiliation(s)
- Chenchen Zhuang
- Hypertension Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Xufei Luo
- School of Public Health, Lanzhou University, Lanzhou, China
| | - Wenjuan Wang
- Hypertension Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Runmin Sun
- Hypertension Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Miaomiao Qi
- Hypertension Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Jing Yu
- Hypertension Center, Lanzhou University Second Hospital, Lanzhou, China
- *Correspondence: Jing Yu
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15
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Hossain MA, Sharfaraz A, Hasan MI, Somadder PD, Haque MA, Sarker MR, Alam MM, Wasaf Hasan AM, Sohel M, Rahman MH. Molecular docking and pharmacology study to explore bio-active compounds and underlying mechanisms of Caesalpinia bonducella on polycystic ovarian syndrome. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.101073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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16
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Dall'Asta A, D'Antonio F, Saccone G, Buca D, Mastantuoni E, Liberati M, Flacco ME, Frusca T, Ghi T. Cardiovascular events following pregnancy complicated by pre-eclampsia with emphasis on comparison between early- and late-onset forms: systematic review and meta-analysis. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2021; 57:698-709. [PMID: 32484256 DOI: 10.1002/uog.22107] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 05/19/2020] [Accepted: 05/27/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVE To elucidate whether pre-eclampsia (PE) and the gestational age at onset of the disease (early- vs late-onset PE) have an impact on the risk of long-term maternal cardiovascular complications. METHODS MEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for 'pre-eclampsia', 'cardiovascular disease' and 'outcome'. Inclusion criteria were cohort or case-control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early- vs late-onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type-2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random-effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed. RESULTS Seventy-three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9-2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8-2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6-2.0)), hypertension (OR, 3.93 (95% CI, 3.1-5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4-8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3-1.4)), Type-2 diabetes (OR, 2.14 (95% CI, 1.5-3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3-5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6-7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1-10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early-onset PE, compared to those with previous late-onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0-3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5-21.4)), hypertension (OR, 1.48 (95% CI, 1.3-1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3-1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1-2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1-2.5). CONCLUSIONS Both early- and late-onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early-onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late-onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- A Dall'Asta
- Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Parma, Italy
| | - F D'Antonio
- Center for Fetal Care and High Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy
| | - G Saccone
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - D Buca
- Center for Fetal Care and High Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy
| | - E Mastantuoni
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - M Liberati
- Center for Fetal Care and High Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy
| | - M E Flacco
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - T Frusca
- Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Parma, Italy
| | - T Ghi
- Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Parma, Italy
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17
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Maas AHEM, Rosano G, Cifkova R, Chieffo A, van Dijken D, Hamoda H, Kunadian V, Laan E, Lambrinoudaki I, Maclaran K, Panay N, Stevenson JC, van Trotsenburg M, Collins P. Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists. Eur Heart J 2021; 42:967-984. [PMID: 33495787 PMCID: PMC7947184 DOI: 10.1093/eurheartj/ehaa1044] [Citation(s) in RCA: 162] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/29/2020] [Accepted: 12/08/2020] [Indexed: 12/13/2022] Open
Abstract
Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).
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Affiliation(s)
- Angela H E M Maas
- Department of Cardiology, Director Women’s Cardiac Health Program, Radboud University Medical Center, Geert Grooteplein-Zuid 10, Route 616, 6525GA Nijmegen, The Netherlands
| | - Giuseppe Rosano
- Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy
| | - Renata Cifkova
- Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer Hospital, Vídeňská 800, 140 59 Prague 4, Czech Republic
- Department of Internal Cardiovascular Medicine, First Medical Faculty, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic
| | - Alaide Chieffo
- Interventional Cardiology Unit, IRCCS San Raffaele Hospital, Olgettina Street, 60 - 20132 Milan (Milan), Italy
| | - Dorenda van Dijken
- Department of Obstetrics and Gynaecology, OLVG location West, Jan Tooropstraat 164, 1061 AE Amsterdam, The Netherlands
| | - Haitham Hamoda
- Department Gynaecology, King's College Hospital, Denmark Hill, London SE5 9RS, UK
| | - Vijay Kunadian
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University and Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, M4:146 4th Floor William Leech Building, Newcastle upon Tyne NE2 4HH, UK
| | - Ellen Laan
- Department of Sexology and Psychosomatic Gynaecology, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Irene Lambrinoudaki
- Menopause Clinic, 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Aretaieio Hospital, 30 Panepistimiou Str., 10679 Athens, Greece
| | - Kate Maclaran
- Department Gynaecology, Chelsea and Westminster Hospital, NHS Foundation Trust, 69 Fulham Road London SW10 9NH, UK
| | - Nick Panay
- Department of Gynaecology, Queen Charlotte's & Chelsea and Westminster Hospitals, Imperial College, Du Cane Road, London W12 0HS, UK
| | - John C Stevenson
- Department of Cardiology, National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
| | - Mick van Trotsenburg
- Bureau Gender PRO Vienna and Department of Obstetrics and Gynaecology, University Hospital St. Poelten-Lilienfeld, Probst Führer Straße 4 · 3100 St. Pölten, Austria
| | - Peter Collins
- Department of Cardiology, National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
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18
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Cooney LG, Dokras A. Cardiometabolic Risk in Polycystic Ovary Syndrome: Current Guidelines. Endocrinol Metab Clin North Am 2021; 50:83-95. [PMID: 33518188 DOI: 10.1016/j.ecl.2020.11.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Polycystic ovary syndrome is a common endocrine disorder in reproductive-aged women and is associated with an increased risk of metabolic abnormalities, including obesity, impaired glucose tolerance, diabetes, dyslipidemia, metabolic syndrome, venous thromboembolism, and subclinical atherosclerosis. Clinicians and patients alike need to be aware of these increased risks as well as new international guidelines that recommend frequent screening and active management of metabolic abnormalities. Given that the data on risk of cardiovascular events, such as myocardial infarction and stroke, in women with PCOS is mixed, future large-scale, longitudinal studies are needed to clarify these potential risks.
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Affiliation(s)
- Laura G Cooney
- Department of Obstetrics and Gynecology, University of Wisconsin, Generations Fertility Care, 2365 Deming Way, Middleton, WI 53562, USA
| | - Anuja Dokras
- Department of Obstetrics and Gynecology, University of Pennsylvania, Penn Fertility Care, 3701 Market Street, Suite 800, Philadelphia, PA 19085, USA.
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19
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Huguelet PS, Olson E, Sass A, Bartz S, Hsu S, Cree-Green M. Application of a Standard Cross-Specialty Workup for Diagnosis and Metabolic Screening of Obese Adolescents With Polycystic Ovary Syndrome. J Adolesc Health 2021; 68:589-595. [PMID: 32819830 DOI: 10.1016/j.jadohealth.2020.07.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 07/08/2020] [Accepted: 07/08/2020] [Indexed: 11/15/2022]
Abstract
PURPOSE Polycystic ovary syndrome (PCOS) is a common disorder. The used diagnostic criteria and screening for related metabolic disease in adolescent girls with PCOS vary with medical specialty, causing discrepancies in care. We sought to improve and standardize care to guidelines for adolescents with PCOS and obesity. METHODS This is a quality improvement project in a multispecialty, tertiary care children's hospital. Providers in Adolescent Medicine, Gynecology, Pediatric Endocrinology, and Endocrine-Metabolic clinics participated. Diagnostic testing and metabolic screening data were collected for new patient encounters with PCOS and obesity, with two improvement cycles from December 2012 to March 2017. Providers received education on diagnostics tests and metabolic screening recommendations, and electronic medical record tools were created. The number of diagnostic and metabolic screening tests ordered per cycle and per clinic were analyzed and compared with baseline. RESULTS The preintervention cycle included 74 encounters-44 in Cycle 1 and 58 in Cycle 2. Diagnostic test completeness improved by Cycle 2 (46%-68%) for all clinics. Screening for metabolic disease only improved in Gynecology (27%-71%). Adolescent Medicine, Endocrinology, and Endocrine-Metabolic used note templates, and Adolescent Medicine and Gynecology used order sets. Note templates were associated with more diagnostic tests ordered in Endocrinology (30%-88%; p = .002). CONCLUSIONS Implementation of quality improvement measures improved the number of diagnostic and metabolic screening tests performed in new patient encounters for PCOS, although the most effective strategy varied by clinic type and electronic medical record habits. Similar efforts should be implemented to standardize care at other institutions.
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Affiliation(s)
- Patricia S Huguelet
- Section of Pediatric and Adolescent Gynecology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado.
| | - Emily Olson
- Section of Pediatric and Adolescent Gynecology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado
| | - Amy Sass
- Division of Adolescent Medicine, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado
| | - Sarah Bartz
- Division of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado
| | - Stephanie Hsu
- Division of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado
| | - Melanie Cree-Green
- Division of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado; Center for Women's Health Research, University of Colorado, Aurora, Colorado
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20
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Zhu S, Li Z, Hu C, Sun F, Wang C, Yuan H, Li Y. Imaging-Based Body Fat Distribution in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2021; 12:697223. [PMID: 34566888 PMCID: PMC8458943 DOI: 10.3389/fendo.2021.697223] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 08/19/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Women with polycystic ovary syndrome (PCOS) are generally considered to be central obese and at higher risks of metabolic disturbances. Imaging methods are the golden standards for detecting body fat distribution. However, evidence based on magnetic resonance imaging (MRI) and computed tomography (CT) is conflicting. This study systematically reviewed the imaging-based body fat distribution in PCOS patients and quantitatively evaluated the difference in body fat distribution between PCOS and BMI-matched controls. METHODS PUBMED, EMBASE, and Web of Science were searched up to December 2019, and studies quantitatively compared body fat distribution by MRI, CT, ultrasound, or X-ray absorptiometry (DXA) between women with PCOS and their BMI-matched controls were included. Two researchers independently reviewed the articles, extract data and evaluated the study quality based on Newcastle-Ottawa Scale (NOS). RESULTS 47 studies were included in systematic review and 39 were eligible for meta-analysis. Compared to BMI-matched controls, higher accumulations of visceral fat (SMD 0.41; 95%CI: 0.23-0.59), abdominal subcutaneous fat (SMD 0.31; 95%CI: 0.20-0.41), total body fat (SMD 0.19; 95% CI: 0.06-0.32), trunk fat (SMD 0.47; 95% CI: 0.17-0.77), and android fat (SMD 0. 36; 95% CI: 0.06-0.66) were identified in PCOS group. However, no significant difference was identified in all the above outcomes in subgroups only including studies using golden standards MRI or CT to evaluate body fat distribution (SMD 0.19; 95%CI: -0.04-0.41 for visceral fat; SMD 0.15; 95%CI: -0.01-0.31 for abdominal subcutaneous fat). Moreover, meta-regression and subgroup analyses showed that young and non-obese patients were more likely to accumulate android fat. CONCLUSIONS PCOS women seem to have abdominal fat accumulation when compared with BMI-matched controls. However, MRI- and CT- assessed fat distribution was similar between PCOS and controls, suggesting central obesity may be independent of PCOS. These findings will help us reappraise the relationship between PCOS and abnormal fat deposition and develop specialized lifestyle interventions for PCOS patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO, identifier CRD42018102983.
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Affiliation(s)
- Shiqin Zhu
- School of Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Ji’nan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Ji’nan, China
| | - Zeyan Li
- School of Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
| | - Cuiping Hu
- School of Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Ji’nan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Ji’nan, China
| | - Fengxuan Sun
- School of Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Ji’nan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Ji’nan, China
| | - Chunling Wang
- Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Ji’nan, China
| | - Haitao Yuan
- Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji’nan, China
- Department of Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- *Correspondence: Yan Li, ; Haitao Yuan,
| | - Yan Li
- School of Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Ji’nan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Ji’nan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Ji’nan, China
- Suzhou Research Institute, Shandong University, Suzhou, China
- *Correspondence: Yan Li, ; Haitao Yuan,
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21
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Duică F, Dănilă CA, Boboc AE, Antoniadis P, Condrat CE, Onciul S, Suciu N, Creţoiu SM, Varlas VN, Creţoiu D. Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 2021; 12:614679. [PMID: 33679617 PMCID: PMC7930620 DOI: 10.3389/fendo.2021.614679] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex disorder that affects around 5% to 10% of women of childbearing age worldwide, making it the most common source of anovulatory infertility. PCOS is defined by increased levels of androgens, abnormal ovulation, irregular menstrual cycles, and polycystic ovarian morphology in one or both ovaries. Women suffering from this condition have also been shown to frequently associate certain cardiovascular comorbidities, including obesity, hypertension, atherosclerosis, and vascular disease. These factors gradually lead to endothelial dysfunction and coronary artery calcification, thus posing an increased risk for adverse cardiac events. Traditional markers such as C-reactive protein (CRP) and homocysteine, along with more novel ones, specifically microRNAs (miRNAs), can accurately signal the risk of cardiovascular disease (CVD) in PCOS women. Furthermore, studies have also reported that increased oxidative stress (OS) coupled with poor antioxidant status significantly add to the increased cardiovascular risk among these patients. OS additionally contributes to the modified ovarian steroidogenesis, consequently leading to hyperandrogenism and infertility. The present review is therefore aimed not only at bringing together the most significant information regarding the role of oxidative stress in promoting CVD among PCOS patients, but also at highlighting the need for determining the efficiency of antioxidant therapy in these patients.
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Affiliation(s)
- Florentina Duică
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Cezara Alina Dănilă
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Andreea Elena Boboc
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Panagiotis Antoniadis
- Division of Molecular Diagnostics and Biotechnology, Antisel RO SRL, Bucharest, Romania
| | - Carmen Elena Condrat
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
- Doctoral School of Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- *Correspondence: Carmen Elena Condrat,
| | - Sebastian Onciul
- Department of Cardiology, Clinical Emergency Hospital, Bucharest, Romania
| | - Nicolae Suciu
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
- Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Sanda Maria Creţoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Valentin Nicolae Varlas
- Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, Bucharest, Romania
- Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Dragoş Creţoiu
- Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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22
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Behboudi-Gandevani S, Amiri M, Cheraghi L, Amanollahi Soudmand S, Azizi F, Ramezani Tehrani F. The risk of chronic kidney disease among women with polycystic ovary syndrome: A long-term population-based cohort study. Clin Endocrinol (Oxf) 2020; 93:590-597. [PMID: 32654166 DOI: 10.1111/cen.14284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 06/12/2020] [Accepted: 06/18/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND OBJECTIVE Results of studies focusing on chronic kidney disease (CKD) among women with polycystic ovary syndrome (PCOS) are insufficient and controversial. This study aimed to evaluate the incidence rate of CKD in women with PCOS, compared to a control group of healthy women. METHODS This study was a population-based cohort study conducted from among 1460 reproductive-age women including 156 women with PCOS and 1304 controls. Incidence rates per 1000 person-years of follow-up were calculated for PCOS and control groups. Cox proportional hazards regression with age as the time-scale was used to estimate hazard ratios (HR) and 95% confidence intervals for developing CKD in relation to PCOS in both univariable and multivariable models. RESULTS During a median follow-up of 12.9 years, 330 new cases of CKD were identified, including 25 PCOS women (14.8 per 1000 person-years; 95% CI, 10-22) and 305 healthy controls (21.5 per 1000 person-years; 95% CI, 19.2-24.1). The results of the Cox model showed that the risk of CKD among women with PCOS and healthy women is comparable and women with PCOS did not have a higher risk of developing CKD compared to healthy women (unadjusted HR: 0.883; 95% CI: 0.587-1.328; P = .551). The results remained unchanged after adjustment for potential confounders of smoking status, BMI, hypertension and diabetes at baseline and follow-up of study (multiple adjusted HR: 0.911; 95% CI: 0.600-1.383; P = .661). CONCLUSION Our population-based study with a long-term follow-up period showed that the risk of CKD in PCOS patients was similar to the general female population. Large studies, with long-term follow-up and more diverse phenotypes, are needed to confirm the findings.
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Affiliation(s)
| | - Mina Amiri
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leila Cheraghi
- Department of Biostatistics and Epidemiology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saber Amanollahi Soudmand
- Department of Urology, Labafi Nejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine 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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23
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Amiri M, Ramezani Tehrani F, Behboudi-Gandevani S, Bidhendi-Yarandi R, Carmina E. Risk of hypertension in women with polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Reprod Biol Endocrinol 2020; 18:23. [PMID: 32183820 PMCID: PMC7076940 DOI: 10.1186/s12958-020-00576-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 02/24/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND A limited number of publications have assessed the prevalence of hypertension (HTN) in polycystic ovary syndrome (PCOS) patients with inconclusive results. Since in general populations the occurrence of hypertension is related to age per se, we investigated the prevalence (P) / relative risk (RR) of HTN in pooled patients with PCOS, vs control population among reproductive age women with PCOS, compared to menopause/aging patients. METHODS PubMed, Scopus, ScienceDirect, web of science, and Google scholar were systematically searched for retrieving observational studies published from inception to April 2019 investigating the HTN in patients with PCOS. The primary outcome of interest was pooled P and RR of HTN in reproductive and menopausal/aging women with PCOS compared to control population. RESULTS The pooled prevalence of HTN in reproductive and menopausal/aging women with PCOS was higher than in the control population [(Pooled P: 0.15, 95% CI: 0.12-0.18 vs. Pooled P: 0.09, 95% CI: 0.08-0.10) and (Pooled P: 0.49, 95% CI: 0.28-0.70 vs. Pooled P: 0.40, 95% CI: 0.22-0.57), respectively]. Compared to the control population, pooled relative risk (RR) of HTN patients was increased only in reproductive age PCOS (1.70-fold, 95% CI: 1.43-2.07) but not in menopausal/aging patients who had PCOS during their reproductive years. The same results were obtained for subgroups of population-based studies. Meta-regression analysis of population-based studies showed that the RR of HTN in reproductive age PCOS patients was 1.76-fold than menopausal/aging PCOS patients (P = 0.262). CONCLUSION This meta-analysis confirms a greater risk of HTN in PCOS patients but demonstrates that this risk is increased only in reproductive age women with PCOS, indicating that after menopause, having a history of PCOS may not be as an important predisposing factor for developing HTN.
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Affiliation(s)
- Mina Amiri
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.
| | | | - Razieh Bidhendi-Yarandi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran
- School of public health, Department of Epidemiology and biostatistics, Tehran University of Medical Sciences, Tehran, Iran
| | - Enrico Carmina
- Endocrinology Unit, Department of Health Sciences and Mother and Child Care, University of Palermo, Palermo, Italy
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24
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Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab 2019; 104:3525-3534. [PMID: 30888398 PMCID: PMC6610211 DOI: 10.1210/jc.2018-02385] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Accepted: 03/13/2019] [Indexed: 02/08/2023]
Abstract
CONTEXT To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS. OBJECTIVE To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI. DESIGN Cross-sectional study. PARTICIPANTS Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33). OUTCOME MEASURES Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis. RESULTS All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing. CONCLUSION Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.
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Affiliation(s)
- Stacey L Simon
- Division of Pulmonary Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Laura McWhirter
- Division of Pulmonary Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Cecilia Diniz Behn
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado
| | - Kate M Bubar
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado
| | - Jill L Kaar
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Laura Pyle
- Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Haseeb Rahat
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Yesenia Garcia-Reyes
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Anne-Marie Carreau
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
| | - Kenneth P Wright
- Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado
- Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Kristen J Nadeau
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
- Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Melanie Cree-Green
- Division of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
- Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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25
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Penn CA, Chan J, Mesaros C, Snyder NW, Rader DJ, Sammel MD, Dokras A. Association of serum androgens and coronary artery calcium scores in women. Fertil Steril 2019; 112:586-593. [PMID: 31200968 DOI: 10.1016/j.fertnstert.2019.04.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 03/27/2019] [Accepted: 04/15/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVE To determine the association between serum androgens measured by high-resolution liquid chromatography-mass spectrometry and coronary artery calcium (CAC) scores. DESIGN Cross-sectional study. SETTING Academic institution. PATIENT(S) A total of 239 women, aged 40-75 years, with CAC testing and complete cardiovascular disease risk evaluation. Total T, DHEA, and androstenedione were measured using high-resolution liquid chromatography-mass spectrometry, whereas E2 and sex hormone-binding globulin were measured using commercial assays. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Independent associations between CAC scores and sex steroids. RESULT(S) Overall, 164 subjects had a CAC score < 10, 48 had a CAC score between 10 and 100, and 27 had a score > 100. There were no differences in sex hormone levels between women with CAC scores > 10 vs. CAC scores ≤ 10. In multivariable models adjusting for age, body mass index, and low-density lipoprotein cholesterol, a higher T/E2 ratio was associated with an elevated CAC score, with an unadjusted odds ratio associated with 1-SD change in log-transformed T/E2 of 1.38 (95% confidence interval 1.01-1.89) and adjusted OR 1.02 (95% confidence interval 1.002-1.04). Total T, DHEA, androstenedione, sex hormone-binding globulin, and E2 levels were not associated with increased CAC. CONCLUSION(S) In the general population, there are mixed reports regarding the relationship between serum androgens and risk factors for cardiovascular disease, and limited information on the relationship between androgens and subclinical atherosclerosis. Our study shows that increased androgens relative to estrogens may have a weak but independent association with subclinical atherosclerosis, as measured by CAC scores.
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Affiliation(s)
- Courtney A Penn
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jessica Chan
- Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Clementina Mesaros
- Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Nathaniel W Snyder
- A. J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania
| | - Daniel J Rader
- Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mary D Sammel
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Anuja Dokras
- Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania.
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26
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Lim SS, Kakoly NS, Tan JWJ, Fitzgerald G, Bahri Khomami M, Joham AE, Cooray SD, Misso ML, Norman RJ, Harrison CL, Ranasinha S, Teede HJ, Moran LJ. Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Obes Rev 2019; 20:339-352. [PMID: 30339316 DOI: 10.1111/obr.12762] [Citation(s) in RCA: 149] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Revised: 03/25/2018] [Accepted: 03/30/2018] [Indexed: 01/08/2023]
Abstract
Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta-analysis and meta-regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta-regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high-density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2-hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA-IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.
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Affiliation(s)
- S S Lim
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - N S Kakoly
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - J W J Tan
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - G Fitzgerald
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - M Bahri Khomami
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - A E Joham
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.,Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria, Australia
| | - S D Cooray
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.,Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria, Australia
| | - M L Misso
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - R J Norman
- Robinson Research Institute, University of Adelaide and Fertility SA, Adelaide, South Australia, Australia
| | - C L Harrison
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - S Ranasinha
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - H J Teede
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.,Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria, Australia.,Monash Partners Academic Health Sciences Centre, Melbourne, Victoria, Australia
| | - L J Moran
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.,Robinson Research Institute, University of Adelaide and Fertility SA, Adelaide, South Australia, Australia
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27
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Cardiometabolic risks in polycystic ovary syndrome: long-term population-based follow-up study. Fertil Steril 2018; 110:1377-1386. [DOI: 10.1016/j.fertnstert.2018.08.046] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 08/18/2018] [Accepted: 08/20/2018] [Indexed: 12/23/2022]
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28
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Cooney LG, Dokras A. Beyond fertility: polycystic ovary syndrome and long-term health. Fertil Steril 2018; 110:794-809. [DOI: 10.1016/j.fertnstert.2018.08.021] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 08/08/2018] [Accepted: 08/08/2018] [Indexed: 12/30/2022]
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29
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Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences. Metabolism 2018; 86:33-43. [PMID: 29024702 DOI: 10.1016/j.metabol.2017.09.016] [Citation(s) in RCA: 211] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 09/23/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023]
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during their reproductive ages, associated with a plethora of cardiometabolic consequences, with obesity, insulin resistance and hyperandrogenemia playing a major role in the degree of such manifestations. These consequences include increased risk of glucose intolerance and diabetes mellitus (both type 2 and gestational), atherogenic dyslipidemia, systemic inflammation, non-alcoholic fatty liver disease, hypertension and coagulation disorders. Whether this cluster of metabolic abnormalities is also translated in increased cardiovascular disease (CVD) morbidity and mortality in later life, remains to be established. Data so far based on markers of subclinical atherosclerosis as well as retrospective and prospective cohort studies indicate a possible increased CVD risk, mainly for coronary heart disease. Future studies are needed to further elucidate this issue.
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Affiliation(s)
- Panagiotis Anagnostis
- First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Basil C Tarlatzis
- First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Robert P Kauffman
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center School of Medicine, Amarillo, TX, USA
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30
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Scicali R, Rosenbaum D, Di Pino A, Giral P, Cluzel P, Redheuil A, Piro S, Rabuazzo AM, Purrello F, Bruckert E, Gallo A. An increased waist-to-hip ratio is a key determinant of atherosclerotic burden in overweight subjects. Acta Diabetol 2018; 55:741-749. [PMID: 29680968 DOI: 10.1007/s00592-018-1144-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Accepted: 04/09/2018] [Indexed: 12/24/2022]
Abstract
AIMS The association of overweight status and cardiovascular disease is not clear. In this study we aimed to investigate coronary atherosclerotic disease, evaluated as coronary artery calcium score (CACs), in overweight patients with or without abdominal obesity as defined by waist-to-hip ratio (WHR). METHODS We enrolled 276 patients aged between 40 and 70 years, with a body mass index of 25-29.9 kg/m2 and at least one cardiovascular risk factor. Exclusion criteria were history of diabetes, cardiovascular or renal disease. Patients were stratified in high WHR (H-WHR) or low WHR (L-WHR) group according to WHR (≥ 0.85 for women and ≥ 0.90 for men) and underwent multi-detector computed tomography for CACs. Mean carotid intima-media thickness (IMT) and plaque presence were equally assessed. RESULTS CACs was higher in the H-WHR group compared to L-WHR (9.05 [0.0-83.48] vs 0.0 [0.0-64.7] AU, p < 0.01); the prevalence of CACs > 0 in the H-WHR group was significantly higher than subjects with L-WHR (59.6% vs 38.5%, p < 0.001). Moreover, H-WHR group had higher mean IMT (0.64 [0.56-0.72] vs 0.59 [0.55-0.67] mm, p < 0.05) and higher carotid plaque prevalence (63.7% vs 50.8%, p < 0.05) compared to subjects with L-WHR. Logistic regression showed that H-WHR was associated with presence of CACs and carotid plaque (p < 0.01). In a multiple linear regression, WHR was positively associated with CACs and IMT (p < 0.01). CONCLUSIONS H-WHR is a marker of coronary and peripheral atherosclerotic burden in overweight patients.
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Affiliation(s)
- Roberto Scicali
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122, Catania, Italy
| | - David Rosenbaum
- Cardiovascular Prevention Unit, of Metabolism and Endocrinology Service; Paris Hospital Public Assistance, Pitié-Salpêtrière Hospital Group - Pierre et Marie Curie University, Paris, France
- UPMC Univ Paris 06, INSERM 1146, - CNRS 7371, Laboratoire d'imagerie Biomédicale, Sorbonne Universités, Paris, France
| | - Antonino Di Pino
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122, Catania, Italy
| | - Philippe Giral
- Cardiovascular Prevention Unit, of Metabolism and Endocrinology Service; Paris Hospital Public Assistance, Pitié-Salpêtrière Hospital Group - Pierre et Marie Curie University, Paris, France
- Dyslipoproteinemia and Atherosclerosis Research Unit, UMRS 939, National Institute for Health and Medical Research (INSERM) and Pierre et Marie Curie University (UPMC - Paris VI), Paris, France
| | - Philippe Cluzel
- UPMC Univ Paris 06, INSERM 1146, - CNRS 7371, Laboratoire d'imagerie Biomédicale, Sorbonne Universités, Paris, France
- Département d'imagerie cardiovasculaire et de radiologie interventionnelle, Pôle Imagerie-Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Alban Redheuil
- UPMC Univ Paris 06, INSERM 1146, - CNRS 7371, Laboratoire d'imagerie Biomédicale, Sorbonne Universités, Paris, France
- Département d'imagerie cardiovasculaire et de radiologie interventionnelle, Pôle Imagerie-Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Salvatore Piro
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122, Catania, Italy
| | - Agata Maria Rabuazzo
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122, Catania, Italy
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi Hospital, University of Catania, Via Palermo 636, 95122, Catania, Italy.
| | - Eric Bruckert
- Cardiovascular Prevention Unit, of Metabolism and Endocrinology Service; Paris Hospital Public Assistance, Pitié-Salpêtrière Hospital Group - Pierre et Marie Curie University, Paris, France
- Dyslipoproteinemia and Atherosclerosis Research Unit, UMRS 939, National Institute for Health and Medical Research (INSERM) and Pierre et Marie Curie University (UPMC - Paris VI), Paris, France
| | - Antonio Gallo
- Cardiovascular Prevention Unit, of Metabolism and Endocrinology Service; Paris Hospital Public Assistance, Pitié-Salpêtrière Hospital Group - Pierre et Marie Curie University, Paris, France
- UPMC Univ Paris 06, INSERM 1146, - CNRS 7371, Laboratoire d'imagerie Biomédicale, Sorbonne Universités, Paris, France
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Hallajzadeh J, Khoramdad M, Karamzad N, Almasi-Hashiani A, Janati A, Ayubi E, Pakzad R, Sullman MJM, Safiri S. Metabolic syndrome and its components among women with polycystic ovary syndrome: a systematic review and meta-analysis. J Cardiovasc Thorac Res 2018; 10:56-69. [PMID: 30116503 PMCID: PMC6088762 DOI: 10.15171/jcvtr.2018.10] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 04/27/2018] [Indexed: 01/24/2023] Open
Abstract
Introduction: The objectives of this study were to provide an estimate of the prevalence of metabolic syndrome (MetS ) and its components among women with PCOS; and calculate the odds ratio (OR) for MetS (using different definitions of MetS) in women with PCOS, compared to healthy controls.
Methods: All of the relevant databases were used to search for appropriate articles that were published during the period 2003-2016. We included observational studies (cross-sectional, comparative cross-sectional) among women who met the inclusion criteria. The random-effect models were used to pool the prevalence of MetS and its components among PCOS women. This model was also applied to the pooled OR assessing the association between MetS and PCOS.
Results: The pooled prevalence of MetS among PCOS women was found to be 26.30% (95% CI: 23.68–28.93), but varied from 7.10% (95% CI: 1.64-12.56) to 37.50% (95% CI: 28.84-46.16), depending upon the diagnostic criteria used. Low high-density lipoprotein cholesterol (HDL) - 61.87% (95% CI: 53.31–70.43) and high waist circumference (WC)- 52.23% (95% CI: 43.84–60.61) were the most common components of MetS in PCOS women. Compared to healthy controls, the overall pooled (OR) of MetS in PCOS patients was 2.09 (95% CI: 1.67-2.60), but this ranged from 0.31 (95% CI: 0.13-0.74) to 4.69 (95% CI: 2.09-10.52), depending upon the diagnostic criteria used.
Conclusion: Women with PCOS had a much higher prevalence of MetS than was found among the healthy controls. Furthermore, as low HDL and high WC were the most common components of MetS in PCOS women, these two components specifically need to be addressed in prevention strategies.
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Affiliation(s)
- Jamal Hallajzadeh
- Managerial Epidemiology Research Center, Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Maliheh Khoramdad
- Department of Epidemiology and Biostatistics, Faculty of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nahid Karamzad
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Almasi-Hashiani
- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Ali Janati
- Iranian Center of Excellence in Health Management, Department of Health Services Management, School of Management and Medical Informatics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Erfan Ayubi
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran
| | - Mark J M Sullman
- Middle East Technical University, Northern Cyprus Campus, Güzelyurt/Morphou, Northern Cyprus
| | - Saeid Safiri
- Managerial Epidemiology Research Center, Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran.,Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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32
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Zoet GA, Meun C, Benschop L, Boersma E, Budde RPJ, Fauser BCJM, de Groot CJM, van der Lugt A, Maas AHEM, Moons KGM, Roeters van Lennep JE, Roos-Hesselink JW, Steegers EAP, van Rijn BB, Laven JSE, Franx A, Velthuis BK. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study. BMC WOMENS HEALTH 2017; 17:60. [PMID: 28784118 PMCID: PMC5547459 DOI: 10.1186/s12905-017-0415-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 08/01/2017] [Indexed: 01/30/2023]
Abstract
Background Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). Methods Women of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. Discussion Initial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. Trial registration Netherlands Trial Register, NTR5531. Date registered: October 21st, 2015.
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Affiliation(s)
- Gerbrand A Zoet
- Wilhelmina Children's Hospital Birth Center, University Medical Center Utrecht, Lundlaan 6, 3508, AB, Utrecht, The Netherlands.
| | - Cindy Meun
- Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Laura Benschop
- Department of Obstetrics & Gynaecology, University Medical Center Rotterdam, Erasmus MC, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Eric Boersma
- Department of Cardiology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Ricardo P J Budde
- Department of Radiology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Bart C J M Fauser
- Department of Reproductive Medicine & Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Christianne J M de Groot
- Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, 1081, HV, Amsterdam, The Netherlands
| | - Aad van der Lugt
- Department of Radiology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Angela H E M Maas
- Department of Cardiology, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands
| | - Karl G M Moons
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Jeanine E Roeters van Lennep
- Department of Internal Medicine, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Jolien W Roos-Hesselink
- Department of Cardiology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Eric A P Steegers
- Department of Obstetrics & Gynaecology, University Medical Center Rotterdam, Erasmus MC, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Bas B van Rijn
- Wilhelmina Children's Hospital Birth Center, University Medical Center Utrecht, Lundlaan 6, 3508, AB, Utrecht, The Netherlands.,Academic Unit of Human Development and Health, University of Southampton, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, UK
| | - Joop S E Laven
- Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015CE, Rotterdam, The Netherlands
| | - Arie Franx
- Wilhelmina Children's Hospital Birth Center, University Medical Center Utrecht, Lundlaan 6, 3508, AB, Utrecht, The Netherlands
| | - Birgitta K Velthuis
- Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
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Bravo-Alegria J, McCullough LD, Liu F. Sex differences in stroke across the lifespan: The role of T lymphocytes. Neurochem Int 2017; 107:127-137. [PMID: 28131898 PMCID: PMC5461203 DOI: 10.1016/j.neuint.2017.01.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 01/13/2017] [Accepted: 01/20/2017] [Indexed: 12/22/2022]
Abstract
Stroke is a sexually dimorphic disease. Ischemic sensitivity changes throughout the lifespan and outcomes depend largely on variables like age, sex, hormonal status, inflammation, and other existing risk factors. Immune responses after stroke play a central role in how these factors interact. Although the post-stroke immune response has been extensively studied, the contribution of lymphocytes to stroke is still not well understood. T cells participate in both innate and adaptive immune responses at both acute and chronic stages of stroke. T cell responses also change at different ages and are modulated by hormones and sex chromosome complement. T cells have also been implicated in the development of hypertension, one of the most important risk factors for vascular disease. In this review, we highlight recent literature on the lymphocytic responses to stroke in the context of age and sex, with a focus on T cell response and the interaction with important stroke risk factors.
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Affiliation(s)
- Javiera Bravo-Alegria
- Department of Neurology, Univeristy of Texas Health Science Center at Houston, Houston, TX, 77030, United States
| | - Louise D McCullough
- Department of Neurology, Univeristy of Texas Health Science Center at Houston, Houston, TX, 77030, United States
| | - Fudong Liu
- Department of Neurology, Univeristy of Texas Health Science Center at Houston, Houston, TX, 77030, United States.
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34
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Gunning MN, Fauser BCJM. Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life? Climacteric 2017; 20:222-227. [DOI: 10.1080/13697137.2017.1316256] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- M. N. Gunning
- Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - B. C. J. M. Fauser
- Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands
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35
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Garin MC, Butts SF, Sarwer DB, Allison KC, Senapati S, Dokras A. Ghrelin is independently associated with anti-mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome. Endocrine 2017; 55:907-913. [PMID: 28004236 PMCID: PMC5963876 DOI: 10.1007/s12020-016-1210-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 12/10/2016] [Indexed: 12/25/2022]
Abstract
Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.
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Affiliation(s)
- Margaret C Garin
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Samantha F Butts
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - David B Sarwer
- Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Kelly C Allison
- Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Suneeta Senapati
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Anuja Dokras
- Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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36
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Patel SS, Truong U, King M, Ferland A, Moreau KL, Dorosz J, Hokanson JE, Wang H, Kinney GL, Maahs DM, Eckel RH, Nadeau KJ, Cree-Green M. Obese adolescents with polycystic ovarian syndrome have elevated cardiovascular disease risk markers. Vasc Med 2017; 22:85-95. [PMID: 28095749 DOI: 10.1177/1358863x16682107] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Women with polycystic ovarian syndrome (PCOS) have evidence of subclinical cardiovascular disease (CVD). However, insulin resistance, an important factor in the development of CVD in adults, is common in adolescents with PCOS, yet data in adolescents are limited. Therefore, we sought to measure insulin resistance and CVD markers in obese youth with and without PCOS. Thirty-six PCOS and 17 non-PCOS adolescent girls who were obese, sedentary, and non-hypertensive were recruited from clinics located within the Children's Hospital Colorado. Following 3 days of controlled diet and restricted exercise, fasting plasma samples were obtained prior to a hyperinsulinemic euglycemic clamp. PCOS girls were more insulin resistant than controls (glucose infusion rate 5.24±1.86 mg/kg/min vs 9.10±2.69; p<0.001). Girls with PCOS had blood pressure in the normal range, but had greater carotid intima-media thickness (cIMT) (0.49±0.07 mm vs 0.44±0.06; p=0.038), beta stiffness index (5.1±1.3 U vs 4.4±0.9; p=0.037), and reduced arterial compliance (1.95±0.47 mm2/mmHg × 10-1 vs 2.13±0.43; p=0.047). PCOS girls had a normal mean lipid profile, yet had a more atherogenic lipoprotein cholesterol distribution and had persistent elevations of free fatty acids despite hyperinsulinemia (68±28 μmol/mL vs 41±10; p=0.001), both potential contributors to CVD. Free fatty acid concentrations correlated best with all CVD markers. In summary, adolescent girls with PCOS have greater cIMT and stiffer arteries than girls without PCOS, perhaps related to altered lipid metabolism, even when clinical measures of blood pressure and cholesterol profiles are 'normal'. Therefore, management of adolescent PCOS should include assessment of CVD risk factor development.
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Affiliation(s)
- Sonali S Patel
- 1 Department of Pediatrics, Division of Pediatric Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Uyen Truong
- 1 Department of Pediatrics, Division of Pediatric Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Martina King
- 2 Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Annie Ferland
- 2 Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Kerrie L Moreau
- 3 Department of Medicine, Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,4 Denver Veterans Administration Medical Center, Geriatric Research Education and Clinical Center, Denver, CO, USA
| | - Jennifer Dorosz
- 5 Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - John E Hokanson
- 6 Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Hong Wang
- 6 Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Gregory L Kinney
- 6 Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - David M Maahs
- 7 Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Robert H Eckel
- 2 Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Kristen J Nadeau
- 7 Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,8 Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,9 Center for Women's Health Research, Aurora, CO, USA
| | - Melanie Cree-Green
- 7 Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,8 Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.,9 Center for Women's Health Research, Aurora, CO, USA
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37
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Feldman RA, O'Neill K, Butts SF, Dokras A. Antimüllerian hormone levels and cardiometabolic risk in young women with polycystic ovary syndrome. Fertil Steril 2017; 107:276-281. [DOI: 10.1016/j.fertnstert.2016.10.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Revised: 10/03/2016] [Accepted: 10/04/2016] [Indexed: 01/01/2023]
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38
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Gao L, Gu Y, Yin X. High Serum Tumor Necrosis Factor-Alpha Levels in Women with Polycystic Ovary Syndrome: A Meta-Analysis. PLoS One 2016; 11:e0164021. [PMID: 27764100 PMCID: PMC5072730 DOI: 10.1371/journal.pone.0164021] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 09/19/2016] [Indexed: 01/11/2023] Open
Abstract
The objective of the study is to assess the TNF-α levels in PCOS patients and healthy controls. A comprehensive electronic search in Medline, Embase, and the Cochrane Library database was conducted up to July 2016. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty-nine studies with a total of 1960 participants (1046 PCOS patients and 914 controls) were included in this meta-analysis. The TNF-α levels in PCOS patients were significantly higher than those in controls (random-effects, SMD = 0.60, 95% CI = 0.28-0.92, P<0.001). With regard to the subgroup analyses stratified by ethnicity, study quality, methods, and BMI, significantly high TNF-α levels were found in patients with PCOS in almost all of these subgroups. In the subgroup stratified by HOMA-IR ratio and T ratio, significant differences were only observed in the subgroups with HOMA-IR ratio of >1.72(SMD = 0.967, 95% CI = 0.103-1.831, P = 0.028, I2 = 93.5%) and T ratio>2.10 (SMD = 1.420, 95% CI = 0.429-2.411, P = 0.005, I2 = 96.1%). By meta-regression it was suggested that ethnicity might contribute little to the heterogeneity between the included studies. Through cumulative meta-analysis and sensitivity analysis it was supposed that the higher TNF-α levels of PCOS patients compared to healthy controls was stable and reliable. This meta-analysis suggests that the circulating TNF-α levels in women with PCOS are significantly higher than those in healthy controls. It may be involved in promoting insulin resistance and androgen excess of PCOS.
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Affiliation(s)
- Lingling Gao
- Department of Obstetrics and Gynecology, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu, China
| | - Yang Gu
- Department of Obstetrics and Gynecology, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu, China
| | - Xianghua Yin
- Department of Obstetrics and Gynecology, Clinical Medical College of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu, China
- * E-mail:
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39
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Is Xanthine oxidase activity in polycystic ovary syndrome associated with inflammatory and cardiovascular risk factors? J Reprod Immunol 2016; 116:98-103. [PMID: 27295433 DOI: 10.1016/j.jri.2016.06.002] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 06/01/2016] [Accepted: 06/02/2016] [Indexed: 12/18/2022]
Abstract
The aim of this study is to examine women with polycystic ovary syndrome (PCOS) to determine the relationship between xanthine oxidase (XO) and oxidative stress, inflammatory status, and various clinical and biochemical parameters. In this cross-sectional study a total of 83 women including 45 PCOS patients and 38 healthy women were enrolled. We collected blood samples for XO and superoxide dismutase (SOD) activity, hormone levels, cholesterol values, and inflammatory markers. Body mass index (BMI) , waist-to-hip ratio (WHR), and blood pressure were assessed. Blood samples were taken for hormonal levels, cholesterol levels, fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostatic model assessment-insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), C-reactive protein (CRP), white blood cell and neutrophil counts, XO and SOD activities. The basal hormone levels, triglyceride (TG) levels, TG/HDL-C (high density lipoprotein-cholesterol) ratios FPG, FPI and HOMA-IR levels were higher in PCOS patients compared to controls (p<0.05). Platelet and plateletcrit (PCT) values, CRP, and XO activity were significantly increased, however SOD activity was decreased in PCOS patients (p<0.001). XO activity was positively correlated with LH/FSH and TG/HDL ratios, CRP, PCT, FPG, FPI, and HOMA-IR, and negatively correlated with QUICKI levels. In conclusion, XO is a useful marker to assess oxidative stress in PCOS patients. Positive correlations between XO and inflammatory markers and cardiovascular disease risk factors suggest that XO plays an important role in the pathogenesis of PCOS and its metabolic complications.
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40
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Ouyang P, Wenger NK, Taylor D, Rich-Edwards JW, Steiner M, Shaw LJ, Berga SL, Miller VM, Merz NB. Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists. Biol Sex Differ 2016; 7:19. [PMID: 27034774 PMCID: PMC4815158 DOI: 10.1186/s13293-016-0073-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 03/21/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. METHODS The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. RESULTS To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific contributors to CV health and disease. Lack of sex-specific knowledge contributes to the CVD health disparities that women face. CONCLUSIONS The purpose of this review is to encourage investigators to consider ways to increase the usefulness of physiological and psychosocial data obtained from clinical populations, in an effort to improve the understanding of sex differences in clinical CVD research and health-care delivery for women and men.
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Affiliation(s)
- Pamela Ouyang
- />Johns Hopkins University, Baltimore, MD USA
- />Division of Cardiology, Johns Hopkins Bayview Medical Center, 301 Building, Suite 2400, 4940 Eastern Ave, Baltimore, MD 21224 USA
| | | | | | | | | | | | | | | | - Noel Bairey Merz
- />Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA USA
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Morris S, Grover S, Sabin MA. What does a diagnostic label of 'polycystic ovary syndrome' really mean in adolescence? A review of current practice recommendations. Clin Obes 2016; 6:1-18. [PMID: 26568133 DOI: 10.1111/cob.12123] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 09/21/2015] [Accepted: 10/01/2015] [Indexed: 12/20/2022]
Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long-term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label 'PCOS' is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome.
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Affiliation(s)
- S Morris
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - S Grover
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Centre for Hormone Research, Murdoch Childrens Research Institute and The Royal Children's Hospital, Melbourne, Victoria, Australia
| | - M A Sabin
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Centre for Hormone Research, Murdoch Childrens Research Institute and The Royal Children's Hospital, Melbourne, Victoria, Australia
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Behboudi-Gandevani S, Ramezani Tehrani F, Rostami Dovom M, Farahmand M, Bahri Khomami M, Noroozzadeh M, Kabir A, Azizi F. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies. Gynecol Endocrinol 2016; 32:343-353. [PMID: 27052492 DOI: 10.3109/09513590.2015.1117069] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Revised: 10/16/2015] [Accepted: 11/03/2015] [Indexed: 11/13/2022] Open
Abstract
We aimed at investigating whether insulin resistance (IR)/sensitivity are impaired in obese/non-obese polycystic ovary syndrome (PCOS) and obese/non-obese healthy controls. A comprehensive literature search was performed for observational, English language studies. Meta-analysis was performed with the random effects model according to the heterogeneity. Eligible studies, involving 3037 women in four groups of: 1-obese, PCOS; 2-non-obese, PCOS, 3-obese, non-PCOS and 4-Non-obese, non-PCOS were included. Based on the insulin resistance index (HOMA-IR) analysis, the pooled mean (95% Conf. Interval) of HOMA IR in groups 1-4 were 4.38 (3.84, 4.92), 2.68 (2.16, 3.20), 2.44 (2.06, 2.82) and 1.34 (1.06, 1.63), respectively. Meta-analysis showed that group 1 (obese, PCOS patients) statistically have the highest IR and group 4 (non-obese, non-PCOS women) have the highest insulin sensitivity. Group 2 (non-obese, PCOS patients) and group 3 (obese, non-PCOS women) were between this range and they had lower IR than group 1 (obese, PCOS) and lower insulin sensitivity than group 4 (non-obese, non-PCOS). So, there were statistical differences between all groups except between groups 2 and 3. Insulin sensitivity indexes (quickie and ISI), also confirm the IR index (HOMA-IR) results. Based on different IR/sensitivity indexes, we found no evidence of any different effects of BMI ≥ 30 kg/m(2) on IR/sensitivity. In conclusion, PCOS status intensifies the adverse effects of obesity on IR, it has to be appropriately addressed in primary and secondary preventive cares and treatments provided for these women.
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Affiliation(s)
- Samira Behboudi-Gandevani
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Fahimeh Ramezani Tehrani
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Marzieh Rostami Dovom
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Maryam Farahmand
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mahnaz Bahri Khomami
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mahsa Noroozzadeh
- a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Ali Kabir
- c Minimally Invasive Surgery Research Center, Department of Community Medicine, School of Medicine, Iran University of Medical Sciences , Tehran , Iran
| | - Fereidoun Azizi
- b Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran , and
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da Silva AV, de Melo AS, Barboza RP, de Paula Martins W, Ferriani RA, Vieira CS. Levonorgestrel-Releasing Intrauterine System for Women With Polycystic Ovary Syndrome. Reprod Sci 2016; 23:877-84. [DOI: 10.1177/1933719115623648] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Adriana Valerio da Silva
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Anderson Sanches de Melo
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Rebecca Pontelo Barboza
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Wellington de Paula Martins
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Rui Alberto Ferriani
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Carolina Sales Vieira
- Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil
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Regensteiner JG, Golden S, Huebschmann AG, Barrett-Connor E, Chang AY, Chyun D, Fox CS, Kim C, Mehta N, Reckelhoff JF, Reusch JEB, Rexrode KM, Sumner AE, Welty FK, Wenger NK, Anton B. Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus: A Scientific Statement From the American Heart Association. Circulation 2015; 132:2424-47. [PMID: 26644329 DOI: 10.1161/cir.0000000000000343] [Citation(s) in RCA: 234] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Artimani T, Saidijam M, Aflatoonian R, Ashrafi M, Amiri I, Yavangi M, SoleimaniAsl S, Shabab N, Karimi J, Mehdizadeh M. Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS. J Assist Reprod Genet 2015; 33:101-10. [PMID: 26631404 DOI: 10.1007/s10815-015-0620-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 11/12/2015] [Indexed: 11/26/2022] Open
Abstract
PURPOSE The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function. METHODS Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient. RESULTS PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02). CONCLUSIONS Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.
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Affiliation(s)
- Tayebe Artimani
- Anatomy Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Reza Aflatoonian
- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Mahnaz Ashrafi
- Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Iraj Amiri
- Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahnaz Yavangi
- Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Sara SoleimaniAsl
- Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nooshin Shabab
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Jamshid Karimi
- Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mehdi Mehdizadeh
- Anatomy Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Cellular and Molecular Research Center, Faculty of Advanced Technology in Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Pertynska-Marczewska M, Diamanti-Kandarakis E, Zhang J, Merhi Z. Advanced glycation end products: A link between metabolic and endothelial dysfunction in polycystic ovary syndrome? Metabolism 2015; 64:1564-73. [PMID: 26386695 DOI: 10.1016/j.metabol.2015.08.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/16/2015] [Accepted: 08/17/2015] [Indexed: 01/07/2023]
Abstract
Polycystic ovary syndrome (PCOS), a heterogeneous syndrome of reproductive and metabolic alterations, is associated with increased long-term risk of cardiovascular complications. This phenomenon has been linked to an increase in oxidative stress and inflammatory markers. Advanced glycation end products (AGEs) are pro-inflammatory molecules that trigger a state of intracellular oxidative stress and inflammation after binding to their cell membrane receptors RAGE. The activation of the AGE-RAGE axis has been well known to play a role in atherosclerosis in both men and women. Women with PCOS have systemic chronic inflammatory condition even at the ovarian level as represented by elevated levels of serum/ovarian AGEs and increased expression of the pro-inflammatory RAGE in ovarian tissue. Data also showed the presence of sRAGE in the follicular fluid and its potential protective role against the harmful effect of AGEs on ovarian function. Thus, whether AGE-RAGE axis constitutes a link between metabolic and endothelial dysfunction in women with PCOS is addressed in this review. Additionally, we discuss the role of hormonal changes observed in PCOS and how they are linked with the AGE-RAGE axis in order to better understand the nature of this complex syndrome whose consequences extend well beyond reproduction.
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Affiliation(s)
| | - Evanthia Diamanti-Kandarakis
- Department of Medicine, Endocrine Unit, Medical School University of Athens, Mikras Asias 75, Goudi 115002D27, Athens, Greece.
| | - John Zhang
- Reproductive Medicine, New Hope Fertility Center, 4 Columbus Circle, New York, NY, USA.
| | - Zaher Merhi
- Department of Obstetrics and Gynecology, Division of Reproductive Biology, NYU School of Medicine, 180 Varick Street, sixth floor, New York, NY, USA.
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Mahalingaiah S, Diamanti-Kandarakis E. Targets to treat metabolic syndrome in polycystic ovary syndrome. Expert Opin Ther Targets 2015; 19:1561-74. [PMID: 26488852 DOI: 10.1517/14728222.2015.1101067] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Metabolic syndrome is comprised of a combination of the following states: increased insulin resistance, dyslipidemia, cardiovascular disease, and increased abdominal obesity. Women with polycystic ovary syndrome (PCOS) have an increased risk of developing metabolic syndrome over the course of their lives. Metabolic syndrome increases risk of major cardiovascular events, morbidity, quality of life, and overall health care costs. Though metabolic syndrome in women with PCOS is an area of great concern, there is no effective individual medical therapeutic to adequately treat this issue. AREAS COVERED This article will review key aspects of metabolic syndrome in PCOS. We will discuss classic and novel therapeutics to address metabolic syndrome in women with PCOS. We will conclude with the importance of developing strategic interventions to increase the compliance to lifestyle and dietary modification, in addition to appreciation of the emerging pharmaceutical therapeutics available. EXPERT OPINION Innovation in lifestyle modification, including diet, exercise, with and without dedicated stress reduction techniques is the future in treatment of metabolic syndrome in PCOS. Application of novel interventions, such as group medical care, may improve future adherence to lifestyle modification recommendations, in addition to or in combination with pharmaceutical therapeutics.
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Affiliation(s)
- Shruthi Mahalingaiah
- a Department of Obstetrics and Gynecology , Boston University School of Medicine , Boston , MA 02118 , USA
| | - Evanthia Diamanti-Kandarakis
- b Department of Endocrinology, Diabetes & Metabolism , University of Athens Medical School , Athens 11521 , Greece
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Okoroh EM, Boulet SL, George MG, Craig Hooper W. Assessing the intersection of cardiovascular disease, venous thromboembolism, and polycystic ovary syndrome. Thromb Res 2015; 136:1165-8. [PMID: 26489726 DOI: 10.1016/j.thromres.2015.10.022] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 10/06/2015] [Accepted: 10/11/2015] [Indexed: 01/24/2023]
Abstract
INTRODUCTION No study has examined how the relationship between polycystic ovary syndrome (PCOS) and atherosclerotic cardiovascular diseases (aCVD), of ischemic stroke (ISCH), acute myocardial infarction (AMI), and peripheral vascular disease (PAD), differ in the presence of venous thromboembolism (VTE). MATERIALS AND METHODS We performed a cross-sectional analysis using Truven Health Analytics MarketScan® Commercial databases from 2004-2011. The association between women aged 18-64 years with and without PCOS, and aCVD was assessed using VTE-stratified multivariable logistic regression models. RESULTS Overall, women with PCOS were more likely to have aCVD, (aOR, 1.27; 95% CI, 1.10-1.46) especially ISCH (aOR, 1.56; 95% CI, 1.30-1.88), than women without PCOS. When stratified by VTE status, women with PCOS and a VTE diagnosis had a decreased odds of having any aCVD (aOR 0.67; 95% CI, 0.46-0.98), and VTE diagnosis more often preceded the occurrence of ISCH and AMI among women with PCOS compared with women without PCOS. CONCLUSIONS Overall, women with PCOS were more likely to have aCVD, with stroke being the most prevalent manifestation. Although VTE often occurred before any aCVD, it appeared to have an inverse association with the development of ISCH, AMI, and PAD among women with PCOS, suggesting that aggressively treating VTE or aCVD early may limit the chances of developing the other thrombogenic condition among women with PCOS.
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Affiliation(s)
- Ekwutosi M Okoroh
- Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., MS-E64, Atlanta, GA 30333, United States.
| | - Sheree L Boulet
- Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., MS-F74, Atlanta, GA 30333, United States
| | - Mary G George
- Division of Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., MS-F72, Atlanta, GA 30333, United States
| | - W Craig Hooper
- Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd., N.E., MS-E64, Atlanta, GA 30333, United States
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Baer TE, Milliren CE, Walls C, DiVasta AD. Clinical Variability in Cardiovascular Disease Risk Factor Screening and Management in Adolescent and Young Adult Women with Polycystic Ovary Syndrome. J Pediatr Adolesc Gynecol 2015; 28:317-23. [PMID: 26081478 PMCID: PMC4556349 DOI: 10.1016/j.jpag.2014.09.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 09/16/2014] [Accepted: 09/19/2014] [Indexed: 10/24/2022]
Abstract
STUDY OBJECTIVES To review the clinical presentation, evaluation, and management of normal-weight (NW), overweight (OW), and obese (OB) adolescent and young adult women with polycystic ovary syndrome (PCOS) during a 2-year follow-up. DESIGN Retrospective chart review. PARTICIPANTS One hundred seventy-three adolescent and young adult women, aged 12-22 years, diagnosed with PCOS. INTERVENTIONS Demographic, health data, and laboratory measures were abstracted from 3 clinic visits: baseline and 1- and 2-year follow-up. Subjects were classified as NW, OW, or OB. Longitudinal data were analyzed using repeated-measures analysis of variance. MAIN OUTCOME MEASURES Body mass index, self-reported concerns, and lifestyle changes. RESULTS Most patients (73%) were OW or OB. Family history of type 2 diabetes was greater in OW (38%) and OB (53%) patients compared with NW (22%) patients (P = .002). Acanthosis nigricans was identified in OW (62%) and OB (21%) patients but not in NW patients (0%; P < .001). OW and OB patients had higher fasting insulin (P < .001) and lower high-density lipoprotein cholesterol (P = .005) levels than NW patients, although screening rates were low. Body mass index Z-scores decreased in both OW and OB patients over time (0.07 unit/yr, P < .001). CONCLUSIONS Most patients with PCOS were OW or OB. Substantial clinical variability existed in cardiovascular disease (CVD) screening; among those screened, OW and OB patients had greater CVD risk factors. Despite self-reported concerns about weight and diabetes risk among OW and OB patients, no clinically significant change in body mass index percentile occurred. Evidence-based interventions and recommendations for screening tests are needed to address CVD risk in adolescents and young adults with PCOS.
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Affiliation(s)
- Tamara E Baer
- Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts.
| | - Carly E Milliren
- Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts
| | | | - Amy D DiVasta
- Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts; Division of Pediatric and Adolescent Gynecology, Boston Children's Hospital, Boston, Massachusetts
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El Maghraby H, Nafee T, Guiziry D, Elnashar A. Randomized controlled trial of the effects of metformin versus combined oral contraceptives in adolescent PCOS women through a 24month follow up period. MIDDLE EAST FERTILITY SOCIETY JOURNAL 2015. [DOI: 10.1016/j.mefs.2014.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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