|
1
|
Genazzani AD, Genazzani AR. Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance. TOUCHREVIEWS IN ENDOCRINOLOGY 2023; 19:71-77. [PMID: 37313240 PMCID: PMC10258623 DOI: 10.17925/ee.2023.19.1.71] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/28/2023] [Indexed: 06/15/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impairment accounting for most of the clinical signs/symptoms of PCOS.
Collapse
Affiliation(s)
- Alessandro D Genazzani
- Gynaecological Endocrinology Center, Department of Obstetrics and Gynaecology, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea R Genazzani
- Department of Obstetrics and Gynaecology, University of Pisa, Pisa, Italy
| |
Collapse
|
|
2
|
Rakic D, Jakovljevic V, Jovic N, Bicanin Ilic M, Dimitrijevic A, Vulovic T, Arsenijevic P, Sretenovic J, Nikolic M, Petrovich Fisenko V, Bolevich S, Zarkovic G, Joksimovic Jovic J. The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives. Biomedicines 2023; 11:biomedicines11040998. [PMID: 37189616 DOI: 10.3390/biomedicines11040998] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 03/14/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women’s reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium–glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.
Collapse
|
|
3
|
The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review. Metabolites 2023; 13:metabo13010129. [PMID: 36677054 PMCID: PMC9863528 DOI: 10.3390/metabo13010129] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body's gut microbiota, also known as the "second genome," can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.
Collapse
|
|
4
|
Arefhosseini S, Ebrahimi-Mameghani M, Najafipour F, Tutunchi H. Non-alcoholic fatty liver disease across endocrinopathies: Interaction with sex hormones. Front Endocrinol (Lausanne) 2022; 13:1032361. [PMID: 36419770 PMCID: PMC9676462 DOI: 10.3389/fendo.2022.1032361] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/24/2022] [Indexed: 11/09/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent chronic liver disease globally. NAFLD is strongly associated with metabolic syndrome and it has been recently suggested that to rename NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). NAFLD has been studied in different endocrine axes and accumulating body of clinical and experimental studies have suggested that NAFLD is associated with polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism and other endocrine disorders. In fact, endocrine dysfunction may be considered as the major contributor for the development, progression, and severity of NAFLD. In the present comprehensive review, we discussed the epidemiological and clinical evidence on the epidemiology, pathophysiology, and management of NAFLD in endocrine disorders, with an emphasis on the effects of sex-specific hormones/conditions as well as molecular basis of NAFLD development in these endocrine diseases.
Collapse
Affiliation(s)
- Sara Arefhosseini
- Student Research Committee, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzad Najafipour
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
5
|
Ogresta D, Mrzljak A, Cigrovski Berkovic M, Bilic-Curcic I, Stojsavljevic-Shapeski S, Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol 2022; 10:339-355. [PMID: 35528987 PMCID: PMC9039716 DOI: 10.14218/jcth.2021.00268] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, type 2 diabetes mellitus and obesity. It is considered a multisystem disease and there is a strong association with cardiovascular disease and arterial hypertension, which interfere with changes in the coagulation system. Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage. Through a review of the literature, we consider and discuss possible disorders in the coagulation cascade and fibrinolysis, endothelial dysfunction and platelet abnormalities in patients with NAFLD.
Collapse
Affiliation(s)
- Doris Ogresta
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Maja Cigrovski Berkovic
- Department for Endocrinology, Diabetes and Pharmacology, University Hospital Dubrava, Zagreb, Croatia
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
- Department of Diabetes, Endocrinology and Metabolism Disorders, University Hospital Osijek, Osijek, Croatia
| | | | - Lucija Virovic-Jukic
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
- Correspondence to: Lucija Virović-Jukić, University of Zagreb School of Medicine, Department of Medicine; Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Vinogradska cesta 29, Zagreb 10000, Croatia. ORCID: https://orcid.org/0000-0002-6350-317X. Tel: +385-1-3787178, Fax: +385-1-3787448, E-mail:
| |
Collapse
|
|
6
|
Georgescu CE. Polycystic ovary syndrome and nonalcoholic fatty liver disease. POLYCYSTIC OVARY SYNDROME 2022:187-216. [DOI: 10.1016/b978-0-12-823045-9.00007-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
7
|
Asfari MM, Sarmini MT, Baidoun F, Al-Khadra Y, Ezzaizi Y, Dasarathy S, McCullough A. Association of non-alcoholic fatty liver disease and polycystic ovarian syndrome. BMJ Open Gastroenterol 2021; 7:bmjgast-2019-000352. [PMID: 32784205 PMCID: PMC7418668 DOI: 10.1136/bmjgast-2019-000352] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 05/26/2020] [Accepted: 05/28/2020] [Indexed: 12/13/2022] Open
Abstract
Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women. Women with PCOS have androgen excess as a defining feature. They also have increased insulin resistance and obesity, which are also risk factors for non-alcoholic fatty liver disease (NAFLD). However, published data regarding PCOS as independent risk factor for NAFLD remain controversial. Therefore, we conducted this study to evaluate the association between PCOS and NAFLD using a large national database. Methods We identified adult female patients (≥18 years) with PCOS using the National Inpatient Sample database between 2002 and 2014. The control group included patients who did not have a diagnosis of PCOS. Multivariate logistic regression analysis was performed to study the association of NAFLD with PCOS. Results Out of a total of 50 785 354 women, 77 415 (0.15%) had PCOS. These patients were younger (32.7 vs 54.8; p<0.001) and more likely to be obese (29.4% vs 8.6%; p<0.001) compared with non-PCOS patients. However, the PCOS group had less hypertension (23.2% vs 39.8%), dyslipidaemia (12% vs 17.8%) and diabetes mellitus (18.1% vs 18.3%) (p<0.001 for all). Using multivariate logistic regression, patients with PCOS had significantly higher rate of NAFLD (OR 4.30, 95% CI 4.11 to 4.50, p<0.001). Conclusion Our study showed that patients with PCOS have four times higher risk of developing NAFLD compared with women without PCOS. Further studies are needed to assess if specific PCOS treatments can affect NAFLD progression.
Collapse
Affiliation(s)
- Mohammad Maysara Asfari
- Gastroenterology and Hepatology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
| | | | - Firas Baidoun
- Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Yamen Ezzaizi
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Arthur McCullough
- Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| |
Collapse
|
|
8
|
Javed Z, Papageorgiou M, Madden LA, Rigby AS, Kilpatrick ES, Atkin SL, Sathyapalan T. The effects of empagliflozin vs metformin on endothelial microparticles in overweight/obese women with polycystic ovary syndrome. Endocr Connect 2020; 9:563-569. [PMID: 32449697 PMCID: PMC7354739 DOI: 10.1530/ec-20-0173] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/20/2020] [Indexed: 01/13/2023]
Abstract
CONTEXT Endothelial microparticles (EMPs) are novel, surrogate biomarkers of endothelial function and have been shown to be elevated in women with polycystic ovary syndrome (PCOS). It remains poorly understood how pharmacological options for managing PCOS affect EMP levels. OBJECTIVE To characterise and compare the effects of empagliflozin vs metformin on the circulating levels of EMPs in overweight/obese women with PCOS. METHODS This was a randomised, comparative, 12-week single-centre trial conducted at the Academic Diabetes, Endocrinology and Metabolism Research Centre, Hull, UK. This analysis includes data from 39 overweight/obese women with PCOS who completed the study and were randomised to empagliflozin (15 mg/day) (n = 19) or metformin (1500 mg/day) (n = 20). Blood samples were collected at baseline and 12 weeks after treatment and analysed for specific surface proteins (ICAM-1, VCAM-1, PECAM-1, E-selectin and endoglin) expressed by circulating EMPs using flow cytometry. RESULTS In the empagliflozin group, ICAM-1 (P = 0.006), E-selectin (P = 0.016) and VCAM-1 (P = 0.001) EMPs increased significantly following 12 weeks of treatment, but no changes were seen in PECAM-1 (P = 0.93) or endoglin (P = 0.13) EMPs. In the metformin group, VCAM-1 EMPs (P < 0.001) increased significantly after 12 weeks of treatment, whereas all other EMPs remained unchanged. When data were expressed as percentage change from baseline in each group, no significant differences were seen between groups for any biomarker (P-values from 0.22 to 0.80). CONCLUSIONS Short-term administration of empagliflozin and metformin in overweight/obese women with PCOS appear to increase EMPs expressed by endothelial cells during their activation.
Collapse
Affiliation(s)
- Zeeshan Javed
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
- Department of Endocrinology and Diabetes, Pakistan Kidney and Liver Institute and Research Centre, Knowledge City, Lahore, Pakistan
| | - Maria Papageorgiou
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | | | - Alan S Rigby
- Hull York Medical School, University of Hull, Hull, UK
| | - Eric S Kilpatrick
- Department of Pathology, Sidra Medical and Research Center, Doha, Qatar
| | | | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
- Correspondence should be addressed to T Sathyapalan:
| |
Collapse
|
|
9
|
Chakraborty S, Ganie MA, Masoodi I, Jana M, Gupta N, Sofi NY. Fibroscan as a non-invasive predictor of hepatic steatosis in women with polycystic ovary syndrome. Indian J Med Res 2020; 151:333-341. [PMID: 32461397 PMCID: PMC7371053 DOI: 10.4103/ijmr.ijmr_610_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background & objectives: There is limited data on non-alcoholic fatty liver disease (NAFLD) among Indian women with polycystic ovary syndrome (PCOS), and there are no data on the utility of fibroscan in its assessment. The objective of this study was thus to investigate the frequency of hepatic steatosis in young women with PCOS and evaluate the utility of transient elastography (TE) in its assessment. Methods: Seventy women diagnosed with PCOS and 60 apparently healthy women (controls) were enrolled in this pilot study. These women were evaluated for clinical, biochemical and hormonal parameters, transabdominal ultrasonography, dual-energy X-ray absorptiometry and fibroscan assessing liver stiffness measure (LSM) and controlled attenuation parameter (CAP). Other indices such as liver fat score (LFS), lipid accumulation product (LAP), fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio index, hepatic steatosis index (HIS) scores were also calculated. The main outcome measures were the presence of NAFLD in women with PCOS and its correlation with CAP and LSM on TE. Results: Women with PCOS had higher frequency (38.57 vs. 6.67%) of hepatic steatosis than control women as determined by abdominal sonography. The aminotransferases were higher in PCOS group (14.28 vs. 1.7%, P=0.03) even after adjusting for body mass index implying higher non-alcoholic steatohepatitis among young PCOS patients. PCOS women had significantly higher CAP on TE compared to controls (210 vs. 196). CAP had a significant correlation with LFS, LAP and HIS. Interpretation & conclusions: NAFLD is common in young women with PCOS, and fibroscan using TE may be considered as a promising non-invasive diagnostic modality in its early detection.
Collapse
Affiliation(s)
- Semanti Chakraborty
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Mohd Ashraf Ganie
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Ibrahim Masoodi
- Department of Medicine, Division of Medical Gastroenterology, Yenepoya Medical College, Mangaluru, Karnataka, India
| | - Manisha Jana
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | -
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Nandita Gupta
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Nighat Yaseen Sofi
- Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
10
|
Paschou SA, Polyzos SA, Anagnostis P, Goulis DG, Kanaka-Gantenbein C, Lambrinoudaki I, Georgopoulos NA, Vryonidou A. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Endocrine 2020; 67:1-8. [PMID: 31538291 DOI: 10.1007/s12020-019-02085-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 08/27/2019] [Indexed: 02/08/2023]
Abstract
Polycystic ovary syndrome (PCOS) affects 6-15% of women of reproductive age. Nonalcoholic fatty liver disease (NAFLD) affects 25-30% of the general population and its prevalence increases in parallel with the epidemics of obesity and type 2 diabetes mellitus. A growing body of evidence suggests that NAFLD and PCOS quite often co-exist. The aim of this article is to summarize and critically appraise the literature regarding: (1) the rates of co-existence of the two entities, (2) the possible pathophysiological links, (3) the proper diagnostic assessment and (4) the appropriate management of women with NAFLD and PCOS. Data from clinical studies and meta-analyses indicate a higher prevalence of NAFLD in women with PCOS ranging from 34% to 70% compared with 14% to 34% in healthy women. Inversely, women with NAFLD are more often diagnosed with PCOS. Insulin resistance (IR) and hyperandrogenism are two main potential pathophysiological links between the two entities. In this regard, IR seems to interplay with obesity and hyperandrogenism, thus affecting NAFLD and PCOS and being affected by them. Women with PCOS, particularly those with IR and/or hyperandrogenism, are suggested to be screened for NAFLD, while premenopausal women with NAFLD is suggested to be screened for PCOS. Lifestyle recommendations with a change in dietary habits, weight loss and exercise, constitute currently the cornerstone of the management of both NAFLD and PCOS. Insulin sensitizers maybe used for the treatment of these women, while there are limited promising data for the use of liraglutide.
Collapse
Affiliation(s)
- Stavroula A Paschou
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Stergios A Polyzos
- First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios G Goulis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christina Kanaka-Gantenbein
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Irene Lambrinoudaki
- Division of Endocrinology and Diabetes, Second Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Neoklis A Georgopoulos
- Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Medical School, University of Patras, Rio, Patras, Greece
| | - Andromachi Vryonidou
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece
| |
Collapse
|
|
11
|
Lonardo A, Mantovani A, Lugari S, Targher G. NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management. Int J Mol Sci 2019; 20:E2841. [PMID: 31212642 PMCID: PMC6600657 DOI: 10.3390/ijms20112841] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 06/04/2019] [Indexed: 02/07/2023] Open
Abstract
Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.
Collapse
Affiliation(s)
- Amedeo Lonardo
- Operating Unit Internal Medicine-Ospedale Civile di Baggiovara-AOU, 41125 Modena, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy.
| | - Simonetta Lugari
- Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41125 Modena, Italy.
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy.
| |
Collapse
|
|
12
|
Kirk RJ, Madden LA, Peart DJ, Aye MM, Atkin SL, Vince RV. Circulating Endothelial Microparticles Reduce in Concentration Following an Exercise Programme in Women With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 2019; 10:200. [PMID: 30984117 PMCID: PMC6450458 DOI: 10.3389/fendo.2019.00200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 03/11/2019] [Indexed: 11/21/2022] Open
Abstract
Purpose: Endothelial dysfunction is a known comorbidity in women with polycystic ovary syndrome (PCOS). The aim was to assess if supervised, moderate intensity exercise could potentially impact markers of endothelial disruption; endothelial cell derived microparticles (EMP). Methods: The current study investigated the effects of a supervised 8-week moderate intensity exercise programme on EMP in women with PCOS (n = 11) and control women free from any known disease (n = 10). EMP were enumerated via specific antibody (CD105, CD106) labeling and flow cytometry. Results: CD105+MP significantly reduced in women with PCOS from pre to post-exercise programme, with CD105+ MP reducing from 2114 CD105+ MP per μl platelet free plasma (PFP) to 424 CD105+ MP per μl PFP (p = 0.025). Control women showed no significant change in CD105+ MP (p = 0.25) after completing the same exercise programme. CD106+ MP showed no change in either PCOS (p = 0.95) or control groups (p = 0.99). No significant correlations existed with the changes in EMP compared to body composition changes as a result of exercise. Conclusion: Supervised, moderate intensity exercise independent of substantial weight loss reduced circulating CD105+ MP, likely reflecting an improvement in endothelial function in women with PCOS compared to healthy control women. Additionally, EMP may be a useful marker for physical improvement in exercise programmes for clinical populations.
Collapse
Affiliation(s)
- Richard J. Kirk
- Sport, Health and Exercise Science, Faculty of Health Sciences, University of Hull, Kingston upon Hull, United Kingdom
| | - Leigh A. Madden
- Centre of Biomedical Research, Faculty of Health Sciences, University of Hull, Kingston upon Hull, United Kingdom
| | - Daniel J. Peart
- Sport, Health and Exercise Science, Faculty of Health Sciences, University of Hull, Kingston upon Hull, United Kingdom
- Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom
| | - Myint M. Aye
- Faculty of Health Sciences, Hull York Medical School, University of Hull, Kingston upon Hull, United Kingdom
| | - Stephen L. Atkin
- Weill Cornell Medical College, Al Rayyan, Qatar
- Royal College of Surgeons Ireland, Al Sayh, Bahrain
| | - Rebecca V. Vince
- Sport, Health and Exercise Science, Faculty of Health Sciences, University of Hull, Kingston upon Hull, United Kingdom
| |
Collapse
|
|
13
|
Rocha ALL, Faria LC, Guimarães TCM, Moreira GV, Cândido AL, Couto CA, Reis FM. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis. J Endocrinol Invest 2017; 40:1279-1288. [PMID: 28612285 DOI: 10.1007/s40618-017-0708-9] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/05/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. METHODS We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). RESULTS PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. CONCLUSION The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.
Collapse
Affiliation(s)
- A L L Rocha
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - L C Faria
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - T C M Guimarães
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - G V Moreira
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - A L Cândido
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - C A Couto
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - F M Reis
- Department of Obstetrics and Gynecology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
- Division of Human Reproduction, Departments of Obstetrics and Gynecology, Hospital das Clínicas, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 110, 9˚ andar, Belo Horizonte, MG, 30130-100, Brazil.
| |
Collapse
|
|
14
|
Macut D, Božić-Antić I, Bjekić-Macut J, Tziomalos K. MANAGEMENT OF ENDOCRINE DISEASE: Polycystic ovary syndrome and nonalcoholic fatty liver disease. Eur J Endocrinol 2017; 177:R145-R158. [PMID: 28694246 DOI: 10.1530/eje-16-1063] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/26/2017] [Accepted: 05/04/2017] [Indexed: 12/15/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women, with a number of metabolic and reproductive consequences. Obesity, insulin resistance (IR) and type 2 diabetes are prominent metabolic characteristics of PCOS and common factors affecting liver function and generating nonalcoholic fatty liver disease (NAFLD). Multiple genes involved in the synthesis of androgens, cytokines and IR, as well as acquired factors, such as endocrine disruptors, could associate the etiopathogenesis of PCOS and NAFLD. Besides the high prevalence of PCOS in general population, NAFLD was shown to be a frequent condition in transition periods, such as adolescence and menopause. Although liver biopsy is considered to be the gold standard for diagnosing liver damage, its routine use in such a prevalent condition as PCOS can be related to a higher rate of complications. Therefore, it is necessary to be able to diagnose NAFLD using simple and reliable surrogate markers. Recently, fatty liver index and NAFLD fatty liver score analyzed in large cohorts of PCOS women have been shown as accurate markers of liver damage in this metabolically vulnerable population. Lifestyle changes are still the mainstay of the management of NAFLD in PCOS, although prospective randomized controlled clinical studies remain a priority in the field. With regard to medications, metformin may be the drug of choice for treating PCOS patients with NAFLD when pharmacologic therapy is considered. Liraglutide use in obese PCOS has shown favorable effects on the predictors of liver fibrosis. In this review, we aim to summarize the influence of the common risk factors and to discuss the diagnostic approaches and management options for NAFLD in patients with PCOS.
Collapse
Affiliation(s)
- Djuro Macut
- Clinic of Endocrinology, Diabetes and Metabolic Diseases
| | | | - Jelica Bjekić-Macut
- Department of Endocrinology, CHC Bezanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Konstantinos Tziomalos
- First Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| |
Collapse
|
|
15
|
P-selectin, endocan, and some adhesion molecules in obese children and adolescents with non-alcoholic fatty liver disease. Scandinavian Journal of Clinical and Laboratory Investigation 2017; 77:205-209. [DOI: 10.1080/00365513.2017.1292363] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
16
|
Targher G, Rossini M, Lonardo A. Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis? Endocrine 2016; 51:211-21. [PMID: 26024975 DOI: 10.1007/s12020-015-0640-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 05/22/2015] [Indexed: 02/06/2023]
Abstract
Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.
Collapse
Affiliation(s)
- Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126, Verona, Italy.
| | - Maurizio Rossini
- Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Amedeo Lonardo
- Outpatient Liver Clinic and Division of Internal Medicine - Department of Biomedical, Metabolic and Neural Sciences, NOCSAE, Baggiovara, Azienda USL, University of Modena and Reggio Emilia, Modena, Italy
| |
Collapse
|
|
17
|
Kelley CE, Brown AJ, Diehl AM, Setji TL. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol 2014; 20:14172-84. [PMID: 25339805 PMCID: PMC4202347 DOI: 10.3748/wjg.v20.i39.14172] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/11/2014] [Accepted: 04/30/2014] [Indexed: 02/07/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.
Collapse
|
|
18
|
Pallayova M, Taheri S. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies. Clin Obes 2014; 4:243-53. [PMID: 25825857 DOI: 10.1111/cob.12068] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 05/15/2014] [Accepted: 05/28/2014] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.
Collapse
Affiliation(s)
- M Pallayova
- Faculty of Medicine, PJ Safarik University, Kosice, Slovak Republic
| | | |
Collapse
|
|
19
|
Vassilatou E. Nonalcoholic fatty liver disease and polycystic ovary syndrome. World J Gastroenterol 2014; 20:8351-8363. [PMID: 25024594 PMCID: PMC4093689 DOI: 10.3748/wjg.v20.i26.8351] [Citation(s) in RCA: 113] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/18/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.
Collapse
|