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Wu Z, Liang G, Zhang Y, Li R. Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients With Polycystic Ovary Syndrome in East Asia: A Review and Meta-Analysis. Endocr Pract 2025; 31:668-676. [PMID: 39947624 DOI: 10.1016/j.eprac.2025.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/02/2024] [Accepted: 01/24/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVES The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in women with polycystic ovary syndrome (PCOS). Epidemiologic literature regarding the risk factors for MASLD in PCOS women in East Asia is inconsistent. Studies of PCOS and MASLD in East Asia are restricted by limited data and various biases. Therefore, this meta-analysis was conducted. METHODS This meta-analysis followed the MOOSE statement. Relevant studies published before July 13, 2023 were retrieved from the PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wan Fang, KISS, and Japan medical online databases. The related data were extracted, and the weighted mean difference, odds ratios and 95% confidence intervals were calculated. RESULTS Twenty-four studies were included. Through univariate analysis, age, body mass index, waist-to-hip ratio (WHR), blood pressure, alanine transaminase, aspartate transaminase, fasting blood glucose, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), 2-hour postprandial blood glucose, 2 hour insulin, HBA1C, low-density lipoprotein cholesterol, triglyceride, total cholesterol, and testosterone were notably higher in PCOS women with MASLD, with high-density lipoprotein cholesterol markedly lower in PCOS women with MASLD. According to the pooled multivariate analysis, the WHR (P < .001), testosterone (P = .034), and HOMA-IR (P = .02) were substantially greater in PCOS women with MASLD. CONCLUSION MASLD is associated with obesity, IR, and hyperandrogenemia among PCOS women in East Asia. The abnormality of WHR, HOMA-IR, and testosterone suggested early screening of MASLD in this population.
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Affiliation(s)
- Zhao Wu
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Guining Liang
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, Nan Shan School of Guangzhou Medical University, Guangzhou, China
| | - Ying Zhang
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, Nan Shan School of Guangzhou Medical University, Guangzhou, China
| | - Renyuan Li
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, China; Department of Clinical Medicine, Nan Shan School of Guangzhou Medical University, Guangzhou, China.
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Duan H, Gong M, Yuan G, Wang Z. Sex Hormone: A Potential Target at Treating Female Metabolic Dysfunction-Associated Steatotic Liver Disease? J Clin Exp Hepatol 2025; 15:102459. [PMID: 39722783 PMCID: PMC11667709 DOI: 10.1016/j.jceh.2024.102459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 11/13/2024] [Indexed: 12/28/2024] Open
Abstract
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rising due to rapid lifestyle changes. Although females may be less prone to MASLD than males, specific studies on MASLD in females should still be conducted. Previous research has shown that sex hormone levels are strongly linked to MASLD in females. By reviewing a large number of experimental and clinical studies, we summarized the pathophysiological mechanisms of estrogen, androgen, sex hormone-binding globulin, follicle-stimulating hormone, and prolactin involved in the development of MASLD. We also analyzed the role of these hormones in female MASLD patients with polycystic ovarian syndrome or menopause, and explored the potential of targeting sex hormones for the treatment of MASLD. We hope this will provide a reference for further exploration of mechanisms and treatments for female MASLD from the perspective of sex hormones.
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Affiliation(s)
- Huiyan Duan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Minmin Gong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Fernández-Alonso AM, Chedraui P, Pérez-López FR. Nonalcoholic fatty liver disease risk in polycystic ovary syndrome patients. Gynecol Endocrinol 2024; 40:2359031. [PMID: 38813954 DOI: 10.1080/09513590.2024.2359031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/17/2024] [Indexed: 05/31/2024] Open
Affiliation(s)
- Ana M Fernández-Alonso
- Department of Obstetrics and Gynecology, Torrecárdenas University Hospital, Almería, Spain
| | - Peter Chedraui
- Escuela de Posgrado en Salud, Universidad Espíritu Santo, Samborondón, Ecuador
| | - Faustino R Pérez-López
- Faculty of Medicine, Aragón Health Research Institute, University of Zaragoza, Zaragoza, Spain
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Fordham TM, Morelli NS, Garcia-Reyes Y, Ware MA, Rahat H, Sundararajan D, Fuller KNZ, Severn C, Pyle L, Malloy CR, Jin ES, Parks EJ, Wolfe RR, Cree MG. Metabolic effects of an essential amino acid supplement in adolescents with PCOS and obesity. Obesity (Silver Spring) 2024; 32:678-690. [PMID: 38439205 DOI: 10.1002/oby.23988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 12/12/2023] [Accepted: 12/13/2023] [Indexed: 03/06/2024]
Abstract
OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS. METHODS A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.3 ± 6.5 kg/m2, age 15.6 ± 1.3 years). Liver fat, very low-density lipoprotein (VLDL) lipogenesis, and triacylglycerol (TG) metabolism were measured following each 28-day phase of placebo or EAA. RESULTS Compared to placebo, EAA was associated with no difference in body weight (p = 0.673). Two markers of liver health improved: HS was lower (-0.8% absolute, -7.5% relative reduction, p = 0.013), as was plasma aspartate aminotransferase (AST) (-8%, p = 0.004). Plasma TG (-9%, p = 0.015) and VLDL-TG (-21%, p = 0.031) were reduced as well. VLDL-TG palmitate derived from lipogenesis was not different between the phases, nor was insulin sensitivity (p > 0.400 for both). Surprisingly, during the EAA phase, participants reported consuming fewer carbohydrates (p = 0.038) and total sugars (p = 0.046). CONCLUSIONS Similar to studies in older adults, short-term EAA supplementation in adolescents resulted in significantly lower liver fat, AST, and plasma lipids and thus may prove to be an effective treatment in this population. Additional research is needed to elucidate the mechanisms for these effects.
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Affiliation(s)
- Talyia M Fordham
- Department of Nutrition and Exercise Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - Nazeen S Morelli
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Yesenia Garcia-Reyes
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Meredith A Ware
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Haseeb Rahat
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Divya Sundararajan
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kelly N Z Fuller
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Cameron Severn
- Child Health Biostatistics Core, Department of Pediatrics, Section of Endocrinology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Laura Pyle
- Child Health Biostatistics Core, Department of Pediatrics, Section of Endocrinology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
| | - Craig R Malloy
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- VA North Texas Health Care System, Dallas, Texas, USA
| | - Eunsook S Jin
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Elizabeth J Parks
- Department of Nutrition and Exercise Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - Robert R Wolfe
- Department of Geriatrics, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Melanie G Cree
- Department of Pediatrics, Section on Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Butt AS, Devi J. Polycystic ovary syndrome and nonalcoholic fatty liver disease. POLYCYSTIC OVARY SYNDROME 2024:92-99. [DOI: 10.1016/b978-0-323-87932-3.00021-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Guimarães TCM, Taranto DODL, Couto CA, Nardelli MJ, Cândido AL, Hott CDA, Anastácio LR, Reis FM, Rocha ALL, Faria LC. Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study. Clinics (Sao Paulo) 2023; 78:100288. [PMID: 38052105 PMCID: PMC10746390 DOI: 10.1016/j.clinsp.2023.100288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/14/2023] [Accepted: 09/26/2023] [Indexed: 12/07/2023] Open
Abstract
INTRODUCTION Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women. OBJECTIVE To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD. METHOD Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed. RESULTS 87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups. CONCLUSIONS PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.
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Affiliation(s)
| | - Daniela Oliveira de Lima Taranto
- Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Serviço de Diagnóstico por Imagem do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Claudia Alves Couto
- Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Ambulatório de Doença Hepática Gordurosa Não Alcoólica, Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Mateus Jorge Nardelli
- Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Ana Lucia Cândido
- Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Ambulatório de Doença Hepática Gordurosa Não Alcoólica, Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Cristina de Almeida Hott
- Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Lucilene Rezende Anastácio
- Departamento de Alimentos, Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Fernando M Reis
- Ambulatório de Hiperandrogenismo, Serviço de Endocrinologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Ana Luiza Lunardi Rocha
- Ambulatório de Hiperandrogenismo, Serviço de Endocrinologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Luciana Costa Faria
- Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Ambulatório de Doença Hepática Gordurosa Não Alcoólica, Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
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Hong X, Guo Z, Yu Q. Hepatic steatosis in women with polycystic ovary syndrome. BMC Endocr Disord 2023; 23:207. [PMID: 37752440 PMCID: PMC10521461 DOI: 10.1186/s12902-023-01456-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 09/13/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND This multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS). METHODS Patients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition. RESULTS A total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001). CONCLUSION The prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver.
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Affiliation(s)
- Xinyu Hong
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, National Clinical Research Center for Obstetric & Gynecologic Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zaixin Guo
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, National Clinical Research Center for Obstetric & Gynecologic Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Qi Yu
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, National Clinical Research Center for Obstetric & Gynecologic Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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Dumesic DA, Abbott DH, Chazenbalk GD. An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome. J Clin Med 2023; 12:6120. [PMID: 37834765 PMCID: PMC10573644 DOI: 10.3390/jcm12196120] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/18/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today's contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today's obesogenic environment.
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Affiliation(s)
- Daniel A. Dumesic
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA;
| | - David H. Abbott
- Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, WI 53715, USA;
| | - Gregorio D. Chazenbalk
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA;
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Kara O, Arsoy HA, Keskin M. Relationship between nonalcoholic fatty liver disease and hyperandrogenemia in adolescents with polycystic ovary syndrome. Clin Exp Pediatr 2023; 66:395-402. [PMID: 37321582 PMCID: PMC10475859 DOI: 10.3345/cep.2023.00353] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 05/29/2023] [Accepted: 06/07/2023] [Indexed: 06/17/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common in adults with polycystic ovary syndrome (PCOS), and several studies on adults have investigated its influencing factors. However, factors associated with NAFLD in adolescents with PCOS remain unknown. PURPOSE This study aimed to investigate the presence of NAFLD in adolescents with PCOS using the noninvasive methods of vibration-controlled transient elastography (VCTE) and ultrasonography (USG), along with assessing NAFLD-related metabolic and hormonal risk factors. METHODS This study included patients aged 12-18 years who were diagnosed with PCOS according to the Rotterdam criteria. The control group included young women with similar age and body mass index (BMI) z scores, who had menstruated regularly for more than 2 years. Patients with PCOS were divided into hyperandrogenemia and nonhyperandrogenemia groups based on serum androgen level. USG was performed on all patients to evaluate the presence of hepatic steatosis. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed using VCTE (Fibroscan). Clinical, laboratory, and radiological data were compared between groups. RESULTS This study included 124 adolescent girls aged 12-18 years (61 with PCOS, 63 controls). BMI z scores were similar between groups. Waist circumference and total cholesterol, triglyceride, and alanine aminotransferase levels were higher in the PCOS versus the control group. The presence of hepatic steatosis on USG was similar between groups. However, the rate of hepatic steatosis on USG was higher in patients with hyperandrogenic PCOS (P=0.01). LSM and CAP measurements were similar between groups. CONCLUSION No increase in prevalence of NAFLD was observed among adolescents with PCOS. However, hyperandrogenemia is a risk factor for NAFLD. Therefore, adolescents with PCOS and elevated androgen level should be screened for NAFLD.
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Affiliation(s)
- Ozlem Kara
- Department of Pediatric Endocrinology, University of Health Sciences Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Hanife Aysegul Arsoy
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences Bursa City Hospital, Bursa, Turkey
| | - Murat Keskin
- Department of Gastroenterology, School of Medicine, KTO Karatay University, Konya, Turkey
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Manzano-Nunez R, Santana-Dominguez M, Rivera-Esteban J, Sabiote C, Sena E, Bañares J, Tacke F, Pericàs JM. Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression. J Clin Med 2023; 12:856. [PMID: 36769504 PMCID: PMC9917911 DOI: 10.3390/jcm12030856] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/15/2023] [Accepted: 01/19/2023] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD's prevalence, and risk factors in patients with PCOS. METHODS A literature search was performed in MEDLINE, Scopus, and Scielo. First, we performed a MA of proportions to estimate the prevalence of NAFLD in PCOS. Second, we performed meta-analyses of precalculated adjusted odds ratios to examine NAFLD risk factors. Finally, we performed a meta-regression to model how the estimated prevalence changed with changes in prespecified variables. RESULTS We identified 817 articles from the database searches. Thirty-six were included. MA of proportions found a pooled NAFLD prevalence of 43% (95% CI, 35-52%) with high heterogeneity (I2 = 97.2%). BMI, waist circumference, ALT values, HOMA-IR values, free androgen index levels, hyperandrogenism, and triglycerides were associated with significantly higher risk-adjusted odds of NAFLD among patients with PCOS. Meta-regression showed that rises in NAFLD prevalence were mediated through increases in metabolic syndrome prevalence and higher levels of HOMA-IR, free androgen index, and total testosterone. CONCLUSION The prevalence of NAFLD (43%) among PCOS patients is high despite their average young age, with several metabolic and PCOS-specific factors influencing its occurrence. Screening programs may aid in detecting metabolic-associated fatty liver disease and prevent its consequences. Further work is required to establish the burden of liver-related outcomes once NAFLD has progressed in the PCOS population.
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Affiliation(s)
- Ramiro Manzano-Nunez
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Faculty of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
| | | | - Jesus Rivera-Esteban
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Faculty of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
| | - Clara Sabiote
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Elena Sena
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Juan Bañares
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, 10117 Berlin, Germany
| | - Juan M. Pericàs
- Liver Unit, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
- Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Centros de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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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.
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12
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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: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [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.
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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
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13
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Roy S, Abudu A, Salinas I, Sinha N, Cline-Fedewa H, Yaw AM, Qi W, Lydic TA, Takahashi DL, Hennebold JD, Hoffmann HM, Wang J, Sen A. Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice. Endocrinology 2022; 163:bqac127. [PMID: 35933634 PMCID: PMC9419696 DOI: 10.1210/endocr/bqac127] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Indexed: 11/19/2022]
Abstract
In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS.
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Affiliation(s)
- Sambit Roy
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Aierken Abudu
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Irving Salinas
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Niharika Sinha
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Holly Cline-Fedewa
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Alexandra M Yaw
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Wenjie Qi
- Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA
| | - Todd A Lydic
- Collaborative Mass Spectrometry Core, Department of Physiology, Michigan State University, East Lansing, MI, USA
| | | | - Jon D Hennebold
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR, USA
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Hanne M Hoffmann
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
| | - Jianrong Wang
- Department of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI, USA
| | - Aritro Sen
- Reproductive and Developmental Sciences Program, Department of Animal Science, Michigan State University, East Lansing, MI, USA
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14
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Shahbaz M, Almatooq H, Foucambert P, Esbrand FD, Zafar S, Panthangi V, Cyril Kurupp AR, Raju A, Luthra G, Khan S. A Systematic Review of the Risk of Non-alcoholic Fatty Liver Disease in Women With Polycystic Ovary Syndrome. Cureus 2022; 14:e29928. [PMID: 36381833 PMCID: PMC9635930 DOI: 10.7759/cureus.29928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/04/2022] [Indexed: 11/07/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex hormonal disorder associated with complications throughout various body organs. Previous studies have shown evidence of liver disease in some women with PCOS. In this study, we attempted to explore the risk of non-alcoholic fatty liver disease (NAFLD) in PCOS women and the specific factors involved in its development. We searched PubMed, PubMed Central, Medline, and ScienceDirect for articles related to the topic, screened those articles according to our inclusion/exclusion criteria, and conducted a thorough quality check using various quality appraisal tools to select articles relevant to our research. The process was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Checklist 2020. We selected 11 high-quality observational studies for our review. Studies from various countries were included, and all studies demonstrated an increased prevalence of NAFLD in PCOS patients compared to healthy controls. Although insulin resistance, obesity, and increased androgens contribute to the increase in the risk of NAFLD in these patients, hyperandrogenism was the most influential risk factor in four of these studies. Two studies explored the degree of NAFLD in these patients using transient elastography (TE). They concluded that PCOS was significantly associated with hepatic steatosis (HS) rather than hepatic fibrosis in most patients. PCOS patients have an increased risk of developing NAFLD, particularly HS, and hyperandrogenism seems to be the main determinant. Therefore, effort should be put into screening and monitoring these patients to manage the disease. TE may be a useful method for monitoring the natural history of NAFLD in these patients, which requires further exploration.
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Affiliation(s)
- Mahrukh Shahbaz
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Halah Almatooq
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Paul Foucambert
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Faith D Esbrand
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sana Zafar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Venkatesh Panthangi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Anjumol Raju
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Gaurav Luthra
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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15
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Nagral A, Bangar M, Menezes S, Bhatia S, Butt N, Ghosh J, Manchanayake JH, Mahtab MA, Singh SP. Gender Differences in Nonalcoholic Fatty Liver Disease. Euroasian J Hepatogastroenterol 2022; 12:S19-S25. [PMID: 36466099 PMCID: PMC9681575 DOI: 10.5005/jp-journals-10018-1370] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2023] Open
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) has currently emerged as the most common liver disorder in both developed and developing countries. It has been observed that NAFLD exhibits sexual dimorphism, and there is limited understanding on the sex differences in adults with NAFLD. Nonalcoholic fatty liver disease shows marked differences in prevalence and severity with regards to gender. There are considerable biological disparities between males and females attributed to differences in the chromosomal makeup and sex hormone levels, distinct from the gender differences resulting from the sociocultural influences that lead to differences in lifestyle, which have a significant impact on the pathogenesis of this complex disorder. A multitude of factors contributes to the gender disparities seen and need to be researched in-depth to better understand the mechanisms behind them and the therapeutic measures that can be taken. In this article, we will review the gender disparities seen in NAFLD, as well as recent studies highlighting certain gender-specific factors contributing to its varying prevalence and severity. HOW TO CITE THIS ARTICLE Nagral A, Bangar M, Menezes S, et al. Gender Differences in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S19-S25.
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Affiliation(s)
- Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India; Apollo Hospital, Navi Mumbai, Maharashtra, India
| | - Manisha Bangar
- Division of Gastroenterology and Hepatology, Century Hospitals, Hyderabad, Telangana, India
| | - Sherna Menezes
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
| | - Shobna Bhatia
- Department of Gastroenterology, Sir HN Reliance Foundation Hospital, Mumbai, Maharashtra, India
| | - Nazish Butt
- Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
| | - Jhumur Ghosh
- Department of Hepatology, MH Samorita Hospital and Medical College, Dhaka, Bangladesh
| | | | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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16
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Doycheva I, Ehrmann DA. Nonalcoholic fatty liver disease and obstructive sleep apnea in women with polycystic ovary syndrome. Fertil Steril 2022; 117:897-911. [PMID: 35512974 DOI: 10.1016/j.fertnstert.2022.03.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/24/2022] [Accepted: 03/29/2022] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea are frequently associated with polycystic ovary syndrome (PCOS) but remain underrecognized. Women with PCOS have a 2-4 times higher risk of NAFLD independent of body mass index than healthy weight-matched controls. Insulin resistance and hyperandrogenemia together play a central role in the pathogenesis of NAFLD. Timely diagnosis of NAFLD is important because its progression can lead to nonalcoholic steatohepatitis and/or advanced liver fibrosis that can eventually result in liver-related mortality. The presence of NAFLD has also been associated with increased risks of type 2 diabetes, cardiovascular events, overall mortality, and extrahepatic cancers. The treatment of NAFLD in PCOS should include lifestyle interventions. Glucagon-like peptide 1 receptor agonists have shown promising results in patients with PCOS and NAFLD, but future randomized trails are needed to confirm this benefit. Likewise, the use of combined oral estrogen-progestin contraceptives may provide a benefit by decreasing hyperandrogenemia. Sleep disordered breathing is common among women with PCOS and is responsible for a number of cardiometabolic derangements. Obstructive sleep apnea is most often found in overweight and obese women with PCOS, but as is the case with NAFLD, its prevalence exceeds that of women who are of similar weight without PCOS. Left untreated, obstructive sleep apnea can precipitate or exacerbate insulin resistance, glucose intolerance, and hypertension.
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Affiliation(s)
- Iliana Doycheva
- Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, Illinois
| | - David A Ehrmann
- Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, Illinois.
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17
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Hassan S, Kaakinen MA, Draisma H, Zudina L, Ganie MA, Rashid A, Balkhiyarova Z, Kiran GS, Vogazianos P, Shammas C, Selvin J, Antoniades A, Demirkan A, Prokopenko I. Bifidobacterium Is Enriched in Gut Microbiome of Kashmiri Women with Polycystic Ovary Syndrome. Genes (Basel) 2022; 13:379. [PMID: 35205422 PMCID: PMC8871983 DOI: 10.3390/genes13020379] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/08/2022] [Accepted: 02/15/2022] [Indexed: 12/12/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is remarkably understudied in Indian women who have a higher incidence of PCOS as compared to other ethnic populations. During the regional PCOS screening program among young women, we recruited 19 drug naive women with PCOS and 20 control women at the Sher-i-Kashmir Institute of Medical Sciences, Kashmir, North India. We profiled the gut microbiome in faecal samples by 16S rRNA sequencing and included 40/58 operational taxonomic units (OTUs) detected in at least 1/3 of the subjects with relative abundance (RA) ≥ 0.1%. We compared the RAs at a family/genus level in PCOS/non-PCOS groups and their correlation with 33 metabolic and hormonal factors, and corrected for multiple testing, while taking the variation in day of menstrual cycle at sample collection, age and BMI into account. Five genera were significantly enriched in PCOS cases: Sarcina, Megasphaera, and previously reported for PCOS Bifidobacterium, Collinsella and Paraprevotella confirmed by different statistical models. At the family level, the relative abundance of Bifidobacteriaceae was enriched, whereas Peptococcaceae was decreased among cases. We observed increased relative abundance of Collinsella and Paraprevotella with higher fasting blood glucose levels, and Paraprevotella and Alkalibacterium with larger hip, waist circumference, weight, and Peptococcaceae with lower prolactin levels. We also detected a novel association between Eubacterium and follicle-stimulating hormone levels and between Bifidobacterium and alkaline phosphatase, independently of the BMI of the participants. Our report supports that there is a relationship between gut microbiome composition and PCOS with links to specific reproductive health metabolic and hormonal predictors in Indian women.
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Affiliation(s)
- Saqib Hassan
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK; (S.H.); (M.A.K.); (H.D.); (Z.B.)
- Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry 605014, India;
| | - Marika A. Kaakinen
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK; (S.H.); (M.A.K.); (H.D.); (Z.B.)
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
| | - Harmen Draisma
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK; (S.H.); (M.A.K.); (H.D.); (Z.B.)
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
| | - Liudmila Zudina
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
| | - Mohd A. Ganie
- Department of Endocrinology, Sheri-Kashmir Institute of Medical Sciences (SKIMS), Srinagar 190011, India; (M.A.G.); (A.R.)
| | - Aafia Rashid
- Department of Endocrinology, Sheri-Kashmir Institute of Medical Sciences (SKIMS), Srinagar 190011, India; (M.A.G.); (A.R.)
| | - Zhanna Balkhiyarova
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK; (S.H.); (M.A.K.); (H.D.); (Z.B.)
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
| | - George S. Kiran
- Department of Food Science and Technology, School of Life Sciences, Pondicherry University, Puducherry 605014, India;
| | | | | | - Joseph Selvin
- Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry 605014, India;
| | | | - Ayse Demirkan
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
- Department of Genetics, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Inga Prokopenko
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK; (S.H.); (M.A.K.); (H.D.); (Z.B.)
- Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; (L.Z.); (A.D.)
- Laboratory UMR 8199-EGID, Institut Pasteur de Lille, CNRS, University of Lille, F-59000 Lille, France
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18
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Ware MA, Kaar JL, Behn CD, Bartlette K, Carreau AM, Lopez-Paniagua D, Scherzinger A, Xie D, Rahat H, Garcia-Reyes Y, Nadeau KJ, Cree-Green M. Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity. Obesity (Silver Spring) 2022; 30:191-200. [PMID: 34932884 PMCID: PMC10786704 DOI: 10.1002/oby.23317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/23/2021] [Accepted: 09/17/2021] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Adolescents with polycystic ovary syndrome (PCOS) and obesity can have insulin resistance, dysglycemia, and hepatic steatosis. Excess pancreatic fat may disturb insulin secretion and relate to hepatic fat. Associations between pancreatic fat fraction (PFF) and metabolic measures in PCOS were unknown. METHODS This secondary analysis included 113 sedentary, nondiabetic adolescent girls (age = 15.4 [1.9] years), with or without PCOS and BMI ≥ 90th percentile. Participants underwent fasting labs, oral glucose tolerance tests, and magnetic resonance imaging for hepatic fat fraction (HFF) and PFF. Groups were categorized by PFF (above or below the median of 2.18%) and compared. RESULTS Visceral fat and HFF were elevated in individuals with PCOS versus control individuals, but PFF was similar. PFF did not correlate with serum androgens. Higher and lower PFF groups had similar HFF, with no correlation between PFF and HFF, although hepatic steatosis was more common in those with higher PFF (≥5.0% HFF; 60% vs. 36%; p = 0.014). The higher PFF group had higher fasting insulin (p = 0.026), fasting insulin resistance (homeostatic model assessment of insulin resistance, p = 0.032; 1/fasting insulin, p = 0.028), free fatty acids (p = 0.034), and triglycerides (p = 0.004) compared with those with lower PFF. β-Cell function and insulin sensitivity were similar between groups. CONCLUSIONS Neither PCOS status nor androgens related to PFF. However, fasting insulin and postprandial lipids were worse with higher PFF.
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Affiliation(s)
- Meredith A. Ware
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Modern Human Anatomy, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Rocky Vista University College of Osteopathic Medicine, Parker, Colorado, USA
| | - Jill L. Kaar
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Cecilia Diniz Behn
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado, USA
| | - Kai Bartlette
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado, USA
| | - Anne-Marie Carreau
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Medicine, School of Medicine, Québec CHU Research Center, Laval University, Québec City, Québec, Canada
| | - Dan Lopez-Paniagua
- Department of Radiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Ann Scherzinger
- Department of Radiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Danielle Xie
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Haseeb Rahat
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Rocky Vista University College of Osteopathic Medicine, Parker, Colorado, USA
| | - Yesenia Garcia-Reyes
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kristen J. Nadeau
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Ludeman Family Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Melanie Cree-Green
- Division of Pediatric Endocrinology, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Ludeman Family Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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19
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Wang D, He B. Current Perspectives on Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome. Diabetes Metab Syndr Obes 2022; 15:1281-1291. [PMID: 35494531 PMCID: PMC9048954 DOI: 10.2147/dmso.s362424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/31/2022] [Indexed: 12/29/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common reproductive, endocrine, and metabolic disorders in premenopausal women. Clinically, PCOS is mainly caused by androgen excess and ovarian dysfunction, manifested by anovulatory menstrual cycles, infertility, and hirsutism. In addition, PCOS increases the risk of insulin resistance, obesity, cardiovascular disease, anxiety and depression, dyslipidemia, and endometrial cancer. Nonalcoholic fatty liver disease (NAFLD) is defined as ≥5% fat accumulation in the liver in the absence of remaining secondary causes and has become one of the most common chronic liver diseases worldwide. The prevalence of NAFLD is significantly higher and more severe in women with PCOS, and its pathogenesis can be associated with various risk factors such as hyperandrogenemia, insulin resistance, obesity, chronic low-grade inflammation, and genetic factors. Although there is no definitive solution for the management of NAFLD in PCOS, some progress has been made. Lifestyle modification should be the basis of management, and drugs to improve metabolism, such as insulin sensitizers and glucagon-like peptide-1 agonists, may show better efficacy. Bariatric surgery may also be a treatment of NAFLD in obese women with PCOS. This paper reviews three aspects of prevalence, risk factors, and management, in order to better understand the current state of research on NAFLD in PCOS, to explore the pathogenesis of NAFLD in PCOS, and to encourage further research on the application of drugs in this field.
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Affiliation(s)
- Dongxu Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Bing He
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
- Correspondence: Bing He, Department of Endocrinology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang, 110004, People’s Republic of China, Tel/Fax +86-24-96615-23111, Email
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20
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Falzarano C, Lofton T, Osei-Ntansah A, Oliver T, Southward T, Stewart S, Andrisse S. Nonalcoholic Fatty Liver Disease in Women and Girls With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2022; 107:258-272. [PMID: 34491336 DOI: 10.1210/clinem/dgab658] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Indexed: 12/15/2022]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of liver damage due to excessive hepatic lipid accumulation. Recent research has demonstrated a high prevalence of NAFLD in women with polycystic ovary syndrome (PCOS). RESULTS Strong associations independent of body mass index (BMI) have been found between high androgen levels characteristic of PCOS, as well as insulin resistance, and the presence of NAFLD in these women, suggesting that these factors contribute to liver injury more significantly than obesity. Current studies indicate the occurrence of NAFLD in normal weight women with PCOS in addition to the commonly researched women who are overweight and obese. While the majority of studies address NAFLD in adult, premenopausal women (ages 25-40 years), the occurrence of NAFLD in young and adolescent women has gone largely unaddressed. Research in this field lacks diversity; a majority of studies either focus on populations of White women or are missing demographic information entirely. CONCLUSIONS Future studies should include larger, more racially and ethnically inclusive populations and particular attention should be paid to how excess androgens and insulin resistance contribute to the increased risk of NAFLD seen in women with PCOS of varying weights, ages, and ethnicities. OBJECTIVE AND METHODS Here, we review NAFLD in women with PCOS with subsections focused on the impact of hyperandrogenism, BMI, insulin resistance and age. Most notably, we present the most up-to-date racially and ethnically diverse worldwide prevalence of NAFLD in women with PCOS compared with women without PCOS (51.56% vs 29.64%, P < .001, respectively).
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Affiliation(s)
- Claire Falzarano
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Taylor Lofton
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Adjoa Osei-Ntansah
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Trinitee Oliver
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Taylor Southward
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Salim Stewart
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
| | - Stanley Andrisse
- Howard University College of Medicine, Physiology and Biophysics, Washington, DC, 20059, USA
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21
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Siwatch S, Singh V, Dhaliwal LK, Kumari S, Singh K. Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women. J OBSTET GYNAECOL 2021; 42:957-961. [PMID: 34689689 DOI: 10.1080/01443615.2021.1969346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a frequent occurrence in polycystic ovarian syndrome (PCOS). We studied the frequencies and characteristics of NAFLD in PCOS women. We compared various methods of detection of advanced fibrosis/cirrhosis. One hundred and forty women with PCOS and seventy controls, matched for age, were evaluated for the presence of NAFLD. Anthropometric variables, serum levels of aminotransferases, glucose, lipids and transient elastography were done. Thirty-six percent of the NAFLD patients had abnormal aminotransferases. In women presenting to an infertility clinic, NAFLD was higher in both obese and non-obese PCOS women, being present in 117 (83.6%) of PCOS cases and 32 (45.7%) of non-PCOS controls (p< .001). Fibroscan is helpful in evaluating for liver fibrosis in patients with NAFLD.Impact StatementWhat is already known on this subject? Polycystic ovarian syndrome (PCOS) has been associated with many long-term health complications including endometrial cancer, diabetes, hypertension and metabolic syndrome. The association of PCOS with NAFLD has been suggested. NAFLD is recognised as a leading cause of liver dysfunction which can progress to long-term sequel of cirrhosis.What do the results of this study add? In this study, asymptomatic women seeking treatment of infertility were screened for presence of NAFLD. The study shows a high prevalence of NAFLD in young Indian women. The prevalence was significantly higher in women with PCOS than non-PCOS women.What are the implications of these findings for clinical practice and/or further research? The findings of the study suggest that all infertile women, especially those with PCOS, should be screened for NAFLD. This will help in early identification and management of this condition and to avoid long-term consequences of liver dysfunction and cirrhosis. PCOS is an independent risk factor for the development of NAFLD in obese women. Liver ultrasound, serum levels of transaminases clinch the diagnosis. Short of liver biopsy, non-invasive tests like Fibroscan and NAFLD fibrosis score are useful to assess the stage of fibrosis.
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Affiliation(s)
- Sujata Siwatch
- Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Lakhbir K Dhaliwal
- Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sunita Kumari
- Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Kartar Singh
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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22
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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: 30] [Impact Index Per Article: 7.5] [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.
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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
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23
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Maier S, Wieland A, Cree-Green M, Nadeau K, Sullivan S, Lanaspa MA, Johnson RJ, Jensen T. Lean NAFLD: an underrecognized and challenging disorder in medicine. Rev Endocr Metab Disord 2021; 22:351-366. [PMID: 33389543 PMCID: PMC8893229 DOI: 10.1007/s11154-020-09621-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2020] [Indexed: 12/14/2022]
Abstract
Classically, Non-Alcoholic Fatty Liver Disease (NAFLD) has been thought to be driven by excessive weight gain and obesity. The overall greater awareness of this disorder has led to its recognition in patients with normal body mass index (BMI). Ongoing research has helped to better understand potential causes of Lean NAFLD, the risks for more advanced disease, and potential therapies. Here we review the recent literature on prevalence, risk factors, severity of disease, and potential therapeutic interventions.
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Affiliation(s)
- Sheila Maier
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Amanda Wieland
- Division of Hepatology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Melanie Cree-Green
- Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Kristen Nadeau
- Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Shelby Sullivan
- Division of Gastroenterology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Miguel A Lanaspa
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA
| | - Richard J Johnson
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA
| | - Thomas Jensen
- Division of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
- Division of Endocrinology, University of Colorado, Denver, Denver, CO, USA.
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24
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Gerges SH, Wahdan SA, Elsherbiny DA, El-Demerdash E. Non-alcoholic fatty liver disease: An overview of risk factors, pathophysiological mechanisms, diagnostic procedures, and therapeutic interventions. Life Sci 2021; 271:119220. [PMID: 33592199 DOI: 10.1016/j.lfs.2021.119220] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/25/2021] [Accepted: 01/29/2021] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.
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Affiliation(s)
- Samar H Gerges
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity Street, Abbasia, Cairo 11566, Egypt
| | - Sara A Wahdan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity Street, Abbasia, Cairo 11566, Egypt
| | - Doaa A Elsherbiny
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity Street, Abbasia, Cairo 11566, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity Street, Abbasia, Cairo 11566, Egypt.
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25
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Won YB, Seo SK, Yun BH, Cho S, Choi YS, Lee BS. Non-alcoholic fatty liver disease in polycystic ovary syndrome women. Sci Rep 2021; 11:7085. [PMID: 33782517 PMCID: PMC8007604 DOI: 10.1038/s41598-021-86697-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/18/2021] [Indexed: 02/01/2023] Open
Abstract
To evaluate risk factors leading to non-alcoholic fatty liver disease (NAFLD) occurrence in polycystic ovarian syndrome (PCOS) women. A retrospective cohort study of a total of 586 women diagnosed with PCOS aged 13-35 years at the gynecology department at a university hospital was done to evaluate PCOS phenotype, metabolic syndrome (MetS) diagnosis, body composition, insulin sensitivity, sex hormones, lipid profile, liver function, and transient elastography (TE). In PCOS women with NAFLD compared to those without, MetS diagnosis (Hazard ratio [HR] 5.6, 95% Confidence interval [CI] 2.2-14.4, p < 0.01) and hyperandrogenism (HA) (HR 4.4, 95% CI 1.4-13.4, p = 0.01) were risk factors significantly associated with subsequent NAFLD occurrence, whereas 2-h insulin level in 75 g glucose tolerance test (GTT) (HR 1.2, 95% CI 0.5-2.5, p = 0.70) and body mass index (BMI) > 25 kg/m2 (HR 2.2, 95% CI 0.6-8.0, p = 0.24) was not. Among NAFLD patients who underwent TE, a higher number of MetS components indicated a worse degree of fibrosis and steatosis. MetS diagnosis and HA at PCOS diagnosis were risk factors associated with NAFLD, while 2-h insulin level in 75 g GTT and obesity were not. Although elevated aspartate aminotransferase levels were significant for NAFLD risk, liver enzyme elevations may not be present until late liver damage. Further prospective studies of PCOS women with MetS or HA are warranted to determine whether patients without liver enzyme elevations should undergo preemptive liver examinations.
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Affiliation(s)
- Young Bin Won
- grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea ,grid.15444.300000 0004 0470 5454Institute of Women’s Life Science, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Kyo Seo
- grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea ,grid.15444.300000 0004 0470 5454Institute of Women’s Life Science, Yonsei University College of Medicine, Seoul, Korea
| | - Bo Hyon Yun
- grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea ,grid.15444.300000 0004 0470 5454Institute of Women’s Life Science, Yonsei University College of Medicine, Seoul, Korea
| | - SiHyun Cho
- grid.15444.300000 0004 0470 5454Institute of Women’s Life Science, Yonsei University College of Medicine, Seoul, Korea ,grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sik Choi
- grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea ,grid.15444.300000 0004 0470 5454Institute of Women’s Life Science, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Seok Lee
- grid.15444.300000 0004 0470 5454Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea
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26
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Shengir M, Chen T, Guadagno E, Ramanakumar AV, Ghali P, Deschenes M, Wong P, Krishnamurthy S, Sebastiani G. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis. JGH OPEN 2021; 5:434-445. [PMID: 33860093 PMCID: PMC8035436 DOI: 10.1002/jgh3.12512] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 01/30/2021] [Accepted: 02/08/2021] [Indexed: 12/13/2022]
Abstract
Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta‐analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Methods Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random‐effect model, and heterogeneity was addressed through I2. Subgroup analyses and meta‐regression for various covariates were performed. Results Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20–2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27–5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85–2.67) and Asia (OR 2.63, 95% CI 2.20–3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44–2.71 and OR 3.39, 95% CI 2.42–4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta‐regression, with a regression coefficient of −2.219 (95% CI −3.927 to −0.511) and −1.929 (95% CI −3.776 to −0.0826), respectively. Conclusions This meta‐analysis indicates that premenopausal PCOS patients are associated with 2.5‐fold increase in the risk of NAFLD, and BMI seems to be the main cofactor.
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Affiliation(s)
- Mohamed Shengir
- Division of Experimental Medicine McGill University Montreal Quebec Canada
| | - Tianyan Chen
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Elena Guadagno
- Harvey E. Beardmore Division of Pediatric Surgery The Montreal Children's Hospital, McGill University Health Centre Montreal Quebec Canada
| | | | - Peter Ghali
- Department of Medicine University of Florida Jacksonville Florida USA
| | - Marc Deschenes
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | - Philip Wong
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
| | | | - Giada Sebastiani
- Department of Medicine McGill University Health Centre Montreal Quebec Canada
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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.
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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
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- 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
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28
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Sharma P, Arora A. Clinical presentation of alcoholic liver disease and non-alcoholic fatty liver disease: spectrum and diagnosis. Transl Gastroenterol Hepatol 2020; 5:19. [PMID: 32258523 DOI: 10.21037/tgh.2019.10.02] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/05/2019] [Indexed: 12/14/2022] Open
Abstract
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are commonest causes of chronic liver disease in developing as well as developed countries. Their incidence has increased due to widespread easy availability of alcohol and sedentary life style of people. NAFLD is a spectrum which includes fatty liver (NAFL) which is considered benign disease, steatohepatitis (NASH) which indicates ongoing injury to liver and cirrhosis of liver. Similarly, ALD spectrum comprises simple steatosis, alcoholic hepatitis, and cirrhosis and its complications. Most of the time there is significant overlap between these diseases and clinical presentation depends upon the stage of liver disease. Most of the NAFLD patients are asymptomatic and diagnosed to have fatty liver while undergoing routine health check up. ALD requires significant history of alcohol intake which is supportive by radiological and biochemical tests. In both NAFLD and ALD patients, liver enzymes are seldom raised beyond five times the upper limit of normal. Liver biopsy is required for diagnosis of NASH as it is a histological diagnosis and sometimes in alcoholic hepatitis for confirmation if diagnosis is in doubt. Non-invasive markers and prognostic scores have been developed for avoiding liver biopsy in assessment and treatment response of NASH and alcoholic hepatitis patients.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
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29
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Li AA, Ahmed, A, Kim D. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gut Liver 2020; 14:168-178. [PMID: 31195434 PMCID: PMC7096231 DOI: 10.5009/gnl19069] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 03/26/2019] [Accepted: 04/05/2019] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.
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Affiliation(s)
- Andrew A. Li
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed,
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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30
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Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology. ACTA ACUST UNITED AC 2020; 56:medicina56030100. [PMID: 32120970 PMCID: PMC7142739 DOI: 10.3390/medicina56030100] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 02/19/2020] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.
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Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab 2020; 35:100937. [PMID: 32244180 PMCID: PMC7115104 DOI: 10.1016/j.molmet.2020.01.001] [Citation(s) in RCA: 248] [Impact Index Per Article: 49.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 12/30/2019] [Accepted: 01/03/2020] [Indexed: 12/16/2022] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited. Scope of review This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions. Major conclusions Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.
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Sarkar M, Terrault N, Chan W, Cedars M, Huddleston H, Duwaerts CC, Balitzer D, Gill RM. Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis. Liver Int 2020; 40:355-359. [PMID: 31627243 PMCID: PMC6980925 DOI: 10.1111/liv.14279] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 10/03/2019] [Accepted: 10/06/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD). METHODS Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status. RESULTS Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2 , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02). CONCLUSION Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.
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Affiliation(s)
- Monika Sarkar
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco (UCSF), California, USA
| | - Norah Terrault
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, California, USA
| | - Wesley Chan
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco (UCSF), California, USA
| | - Marcelle Cedars
- Center for Reproductive Health, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, California, USA
| | - Heather Huddleston
- Center for Reproductive Health, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, California, USA
| | - Caroline C. Duwaerts
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco (UCSF), California, USA
| | - Dana Balitzer
- Department of Pathology, UCSF, San Francisco, California, USA
| | - Ryan M. Gill
- Department of Pathology, UCSF, San Francisco, California, USA
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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: 48] [Impact Index Per Article: 9.6] [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.
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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
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Vallet-Pichard A, Parlati L, Pol S. [Epidemiology of non-alcoholic steatohepatitis. Extent/burden of the problem and its impact on public health]. Presse Med 2019; 48:1459-1467. [PMID: 31757728 DOI: 10.1016/j.lpm.2019.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 08/17/2019] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, the most common cause of chronic liver function augmentation and it will be the most common indication for liver transplantation in 2020. The prevalence of NAFLD has increased over time in line with the increase of obesity and type 2 diabetes. There is a discrepancy between the studies concerning the prevalence of NAFLD because of the different diagnostic methods used (ultrasound or magnetic resonance, fibroscan, controlled attenuation parameter (CAP), histology). Because of its high prevalence the impact of NAFLD in public health is real. Therapeutic advances must be made to better understand the natural history of NAFLD and improve the management of this emerging liver disease.
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Affiliation(s)
- Anaïs Vallet-Pichard
- Hôpital Cochin, département d'hépatologie, 27, rue du Fg-Saint-Jacques, 75014 ParisFrance.
| | - Lucia Parlati
- Hôpital Cochin, département d'hépatologie, 27, rue du Fg-Saint-Jacques, 75014 ParisFrance; AP-HP, université Paris Descartes, 15, rue de l'École de Médecine, 75006 Paris, France
| | - Stanislas Pol
- Hôpital Cochin, département d'hépatologie, 27, rue du Fg-Saint-Jacques, 75014 ParisFrance; AP-HP, université Paris Descartes, 15, rue de l'École de Médecine, 75006 Paris, France; Institut Pasteur, Inserm U1223, UMS-20, 25-28, rue du Docteur-Roux, 75015 Paris France
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Cree-Green M, Carreau AM, Rahat H, Garcia-Reyes Y, Bergman BC, Pyle L, Nadeau KJ. Amino acid and fatty acid metabolomic profile during fasting and hyperinsulinemia in girls with polycystic ovarian syndrome. Am J Physiol Endocrinol Metab 2019; 316:E707-E718. [PMID: 30753112 PMCID: PMC6580169 DOI: 10.1152/ajpendo.00532.2018] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Polycystic ovarian syndrome (PCOS) is associated with insulin resistance (IR) and altered muscle mitochondrial oxidative phosphorylation. IR in adults with obesity and diabetes is associated with changes in amino acid, free fatty acid (FFA), and mitochondrial acylcarnitine (AC) metabolism. We sought to determine whether these metabolites are associated with IR and/or androgens in youth-onset PCOS. We enrolled obese girls with PCOS [ n = 15, 14.5 yr (SD 1.6), %BMI 98.5 (SD 1.0)] and without PCOS [ n = 6, 13.2 yr (SD 1.2), %BMI 98.0 (SD 1.1)]. Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp. Untargeted metabolomics of plasma was performed while fasting and during hyperinsulinemia. Fasting arginine, glutamine, histidine, lysine, phenylalanine, and tyrosine were higher ( P < 0.04 for all but P < 0.001 for valine), as were glutamine and histidine during hyperinsulinemia ( P < 0.03). Higher valine during hyperinsulinemia was associated with IR ( r = 0.59, P = 0.006). Surprisingly, end-clamp AC C4 was lower in PCOS, and lower C4 was associated with IR ( r = -0.44, P = 0.04). End-clamp FFAs of C14:0, C16:1, and C18:1 were higher in PCOS girls, and C16:1 and C18:1 strongly associated with IR ( r = 0.73 and 0.53, P < 0.01). Free androgen index related negatively to short-, medium-, and long-chain AC ( r = -0.41 to -0.71, P < 0.01) but not FFA or amino acids. Obese girls with PCOS have a distinct metabolic signature during fasting and hyperinsulinemia. As in diabetes, IR related to valine and FFAs, with an unexpected relationship with AC C4, suggesting unique metabolism in obese girls with PCOS.
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Affiliation(s)
- Melanie Cree-Green
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus , Aurora, Colorado
- Center for Women's Health Research , Aurora, Colorado
| | - Anne-Marie Carreau
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus , Aurora, Colorado
| | - Haseeb Rahat
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus , Aurora, Colorado
| | - Yesenia Garcia-Reyes
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus , Aurora, Colorado
| | - Bryan C Bergman
- Department of Medicine, Division of Endocrinology and Metabolism, University of Colorado Anschutz Medical Campus , Aurora, Colorado
| | - Laura Pyle
- Department of Biostatistics and Informatics, Colorado School of Public Health , Aurora, Colorado
- Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado
| | - Kristen J Nadeau
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus , Aurora, Colorado
- Center for Women's Health Research , Aurora, Colorado
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Harsha Varma S, Tirupati S, Pradeep TVS, Sarathi V, Kumar D. Insulin resistance and hyperandrogenemia independently predict nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Diabetes Metab Syndr 2019; 13:1065-1069. [PMID: 31336445 DOI: 10.1016/j.dsx.2018.12.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 12/26/2018] [Indexed: 12/16/2022]
Abstract
AIMS To find the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in Asian Indian polycystic ovary syndrome (PCOS) women. MATERIALS AND METHODS This is a prospective, cross-sectional study conducted at a tertiary care hospital from South India. Sixty women fulfilling the Rotterdam (2003) criteria for PCOS were recruited for the study. All participants were evaluated with ultrasound abdomen for fatty liver and additional biochemical investigations including fasting plasma glucose, postprandial plasma glucose, serum insulin, lipid profile and liver function tests. RESULTS The mean age of the study population was 24.06 ± 5.9 (range: 15-39) years. Oligomenorrhea, hirsutism and acne were present in 58 (96.7%), 37 (61.7%) and 33 (55%) women. Mean BMI of the study population was 29.5 ± 5.28 (range: 19.95 to 45.44) kg/m2. Fifty (83.3%) women were obese (BMI: ≥ 25 kg/m2). Twenty-three (38.3%) women with PCOS had NAFLD. Three women each had isolated elevation of alanine transaminase (ALT) and aspartate transaminases (AST) whereas three women had elevation of both. All women with elevated transaminases had NAFLD. By univariate analysis, factors associated with NAFLD were serum total cholesterol, serum insulin, HOMA-IR, hyperandrogenism, ALT and AST. On multiple regression analysis using linear regression, HOMA-IR and hyperandrogenemia were the only significant predictors of NAFLD. CONCLUSION Our study reports NAFLD in more than one third of Asian Indian women with PCOS. In addition to insulin resistance (HOMA-IR), hyperandrogenemia is an independent predictor of NAFLD in women with PCOS.
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Affiliation(s)
- Sree Harsha Varma
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Sunanda Tirupati
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - T V S Pradeep
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Vijaya Sarathi
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
| | - Dileep Kumar
- Department of Endocrinology, Narayana Medical College and Hospital, Nellore, 524003, India.
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Minato S, Sakane N, Kotani K, Nirengi S, Hayashi I, Suganuma A, Yamaguchi K, Takakura K, Nagai N. Prevalence and Risk Factors of Elevated Liver Enzymes in Japanese Women With Polycystic Ovary Syndrome. J Clin Med Res 2018; 10:904-910. [PMID: 30425763 PMCID: PMC6225863 DOI: 10.14740/jocmr3639] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 10/15/2018] [Indexed: 02/06/2023] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-aged women. While PCOS is associated with an increased risk of obesity and insulin resistance, little is known regarding the prevalence of and risk factors for nonalcoholic fatty liver disease (NAFLD) among Japanese women with PCOS. We estimated the prevalence of and risk factors for elevated liver enzymes, as the index of NAFLD, in Japanese women with PCOS. Methods We retrospectively reviewed 102 reproductive-aged women who visited the Department of Gynecology, Kyoto Medical Center in Japan from January 2000 to September 2016. Inclusion criterion was confirmed diagnosis of PCOS using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10) codes. Exclusion criteria were women with a history of liver diseases, missing body mass index (BMI) and serum alanine aminotransferase (ALT) data, and pregnancy. Data regarding age; BMI; and levels of blood glucose, serum lipid, liver enzymes, and sex hormones were obtained from medical records. Elevated liver enzymes was defined as ALT > 19 IU/L. Optimal cutoffs for risk factors for elevated liver enzymes were calculated to determine predictors of elevated liver enzymes using area under the curve (AUC) by receiver-operating characteristics (ROC). Results The prevalence of elevated liver enzymes was 33.3%. BMI was significantly higher in PCOS patients than in those without elevated liver enzymes (25.3 vs. 20.7 kg/m2, P < 0.05). ROC analyses were performed using BMI and blood glucose and testosterone levels because BMI and blood glucose showed differences between the groups and testosterone is related to fatty liver. AUC of the model including BMI and blood glucose and testosterone levels was 0.861 (sensitivity, 66.7%; specificity, 100%). Conclusions These findings suggest that elevated liver enzymes are common in women with PCOS. An algorism using BMI and blood glucose and testosterone levels might be useful to determine elevated liver enzymes in women with PCOS. Our finding may be useful for the study of NAFLD among Japanese women with PCOS since several previous studies have indicated elevated liver enzymes to be related to the potential presence of NAFLD. Further examination, including abdominal ultrasonography and/or liver biopsy data, is required to confirm these results.
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Affiliation(s)
- Satomi Minato
- Graduate School of Human Science and Environment, University of Hyogo, Hyogo, Japan.,Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Kazuhiko Kotani
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.,Division of Community and Family Medicine, Jichi Medical University, Tochigi, Japan
| | - Shinsuke Nirengi
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Ikuyo Hayashi
- Graduate School of Human Science and Environment, University of Hyogo, Hyogo, Japan.,Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Akiko Suganuma
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Ken Yamaguchi
- Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Kenji Takakura
- Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Narumi Nagai
- Graduate School of Human Science and Environment, University of Hyogo, Hyogo, Japan
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Buckley AJ, Thomas EL, Lessan N, Trovato FM, Trovato GM, Taylor-Robinson SD. Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints. Diabetes Res Clin Pract 2018; 144:144-152. [PMID: 30170074 DOI: 10.1016/j.diabres.2018.08.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/08/2018] [Accepted: 08/14/2018] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.
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Affiliation(s)
- Adam J Buckley
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - E Louise Thomas
- University of Westminster, Department of Life Sciences, London, United Kingdom.
| | - Nader Lessan
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - Francesca M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Guglielmo M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Simon D Taylor-Robinson
- Imperial College London, Division of Integrative Systems Medicine and Digestive Health, Department of Surgery and Cancer, London, United Kingdom.
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Merlo E, Silva IV, Cardoso RC, Graceli JB. The obesogen tributyltin induces features of polycystic ovary syndrome (PCOS): a review. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2018; 21:181-206. [PMID: 30015594 DOI: 10.1080/10937404.2018.1496214] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by abnormal reproductive cycles, irregular ovulation, and hyperandrogenism. This complex disorder has its origins both within and outside the hypothalamic-pituitary-ovarian axis. Cardio-metabolic factors, such as obesity and insulin resistance, contribute to the manifestation of the PCOS phenotype. Polycystic ovary syndrome is one of the most common endocrine disorders among women of reproductive age. Growing evidence suggested an association between reproductive and metabolic features of PCOS and exposure to endocrine-disrupting chemicals (EDC), such as bisphenol A. Further, the environmental obesogen tributyltin (TBT) was shown to induce reproductive, metabolic and cardiovascular abnormalities resembling those found in women and animal models of PCOS. However, the causal link between TBT exposure and PCOS development remains unclear. The objective of this review was to summarize the most recent research findings on the potential association between TBT exposure and development of PCOS-like features in animal models and humans.
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Affiliation(s)
- Eduardo Merlo
- a Department of Morphology , Federal University of Espirito Santo , Vitoria, Brazil
| | - Ian V Silva
- a Department of Morphology , Federal University of Espirito Santo , Vitoria, Brazil
| | - Rodolfo C Cardoso
- b Department of Animal Science , Texas A&M University , College Station, TX, USA
| | - Jones B Graceli
- a Department of Morphology , Federal University of Espirito Santo , Vitoria, Brazil
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Wang Y, Zhou W, Wu C, Zhang Y, Lin T, Sun Y, Liu W, Tao T. Circulating osteopontin and its association with liver fat content in non-obese women with polycystic ovary syndrome: a case control study. Reprod Biol Endocrinol 2018; 16:31. [PMID: 29587769 PMCID: PMC5870073 DOI: 10.1186/s12958-018-0331-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Accepted: 02/06/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Osteopontin (OPN) plays an important role in inflammatory processes and insulin resistance. Polycystic ovary syndrome (PCOS) is a reproductive metabolic disease associated with insulin resistance and metabolic abnormalities, including high levels of liver fat content (LFC). The objective of this study was to explore whether circulating OPN independently contributes to elevated LFC in non-obese PCOS patients. METHODS This study included 61 non-obese PCOS patients and 56 age-matched healthy women from Shanghai, China. After an overnight fast, all participants underwent anthropometric measurements, oral glucose tolerance tests, lipid profile and sex hormone measurements. Quantitative measurement of LFC by ultrasonography was performed. OPN concentrations were measured using ELISA. An independent samples t-test and the Mann-Whitney U test were performed to compare variables between the two groups; one-way ANOVA and Kruskal-Wallis test were performed to compare four subgroups of patients. Correlations were determined by Spearman's correlation tests. Stepwise multiple linear regression analyses were performed to assess for independent contributors. A receiver operating characteristic curve with the maximum Youden index was calculated for the optimal cut-off value. RESULTS In non-obese PCOS women, circulating OPN levels were increased in the subgroups with a higher body mass index (BMI) and free androgen index (FAI), and the LFC levels were increased in the elevated OPN subgroups. Moreover, increased OPN was associated with increased FAI and LFC in PCOS women, and the association between OPN and LFC was independent of triglyceride, HOMA-IR and FAI after adjusting for PCOS status in all participants. OPN combined with FAI and hsCRP may better predict NAFLD than WHR in this study cohort. However, there was no significant difference in circulating OPN levels between non-obese PCOS and normal control women. CONCLUSIONS Increased OPN levels may be related to FAI and elevated LFC in non-obese women with PCOS.
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Affiliation(s)
- Yuying Wang
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Wei Zhou
- Department of Emergency, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Chunhua Wu
- Division of Ultrasonography, Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yi Zhang
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Tzuchun Lin
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yun Sun
- Shanghai Key laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China
| | - Wei Liu
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
- Shanghai Key laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
| | - Tao Tao
- Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
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Zhang J, Hu J, Zhang C, Jiao Y, Kong X, Wang W. Analyses of risk factors for polycystic ovary syndrome complicated with non-alcoholic fatty liver disease. Exp Ther Med 2018; 15:4259-4264. [PMID: 29725371 PMCID: PMC5920378 DOI: 10.3892/etm.2018.5932] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 02/15/2018] [Indexed: 12/14/2022] Open
Abstract
The risk factors related to polycystic ovary syndrome (PCOS) patients complicated with non-alcoholic fatty liver disease (NAFLD) were investigated. A total of 188 PCOS patients treated in Shengli Oilfield Central Hospital (Dongying, China) from February 2014 to February 2015 were retrospectively analyzed as PCOS group, and PCOS group was further divided into NAFLD group and non-NAFLD (N-NAFLD) group according to the liver B ultrasound. In the same time-period, 65 healthy people were selected as normal control group. The differences of clinical, biochemical and metabolic indexes were compared. The levels of luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), testosterone (T), free androgen index (FAI), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) index in PCOS group were higher than those in normal control group, but the sex hormone binding globulin (SHBG) level was lower than that in normal control group (P<0.05); there were no statistically significant differences in comparisons of age, body mass index (BMI), waist-hip ratio (WHR), FSH, dehydroepiandrosterone sulfate (DHEAs) and fasting blood glucose (FBG) between the two groups (P>0.05). The prevalence rate of NAFLD in PCOS group (44.68%) was significantly higher than that in control group (24.62%) (P<0.05). The proportion of NAFLD in PCOS patients in obesity group (63.51%) was significantly higher than that in non-obesity group (15.79%) (P<0.05). In PCOS group, NAFLD patients had more obvious metabolic abnormalities [high BMI, WHR, FBG, FINS, HOMA-IR index, total cholesterol (TC) and triglyceride (TG), and low high-density lipoprotein HDL and SHBG] and androgen excess compared with those in N-NAFLD patients (P<0.05). The levels of LH, LH/FSH, FINS and HOMA-IR index in PCOS group complicated with NAFLD were higher than those in control group complicated with NAFLD (P<0.05), but the differences in age, BMI, WHR, FSH and FBG levels were not statistically significant between the two groups (P>0.05). HOMA-IR index, BMI, WHR and TG were independent risk factors for PCOS complicated with NAFLD (P<0.05).
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Affiliation(s)
- Jianhai Zhang
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Jian Hu
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Chunxia Zhang
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Yanni Jiao
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Xiang Kong
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Wei Wang
- Department of Obstetrics and Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
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Abstract
Background Epidemiological and clinical studies have largely demonstrated major differences in the prevalence of metabolic disorders in males and females, but the biological cause of these dissimilarities remain to be elucidated. Mammals are characterized by a major change in reproductive strategies and it is conceivable that these changes subjected females to a significant evolutionary pressure that perfected the coupling between energy metabolism and reproduction. Scope of review This review will address the plausibility that female liver functions diverged significantly from males given the role of liver in the control of metabolism. Indeed, it is well known that the liver is sexually dimorphic, and this might be relevant to explain the lower susceptibility to hepatic diseases and liver-derived metabolic disturbances (such as the cardiovascular diseases) characteristic of females during their fertile period. Furthermore, estrogens and the hepatic ERα play a significant role in liver sexual-specific functions and in the control of metabolic functions. Conclusions A better grasp of the role of male and female sex steroids in the liver of the two sexes may therefore represent an important element to conceive novel treatments aimed at preventing metabolic diseases particularly in ageing women or limiting undesired side effect in the treatment of gender dysphoria.
Liver is a target for estrogens. Liver metabolism is regulated by estrogens. Metabolism and reproduction are reciprocally regulated functions. Liver sexual dimorphism is associated to female reproductive functions. Liver is sexually differentiated neonatally.
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Zhang Y, Meng F, Sun X, Sun X, Hu M, Cui P, Vestin E, Li X, Li W, Wu XK, Jansson JO, Shao LR, Billig H. Hyperandrogenism and insulin resistance contribute to hepatic steatosis and inflammation in female rat liver. Oncotarget 2018; 9:18180-18197. [PMID: 29719598 PMCID: PMC5915065 DOI: 10.18632/oncotarget.24477] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/25/2018] [Indexed: 02/06/2023] Open
Abstract
Women with polycystic ovary syndrome (PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). While insulin resistance is a common trait for both PCOS and NAFLD, hyperandrogenism is also considered to be a key factor contributing to PCOS, and the molecular mechanisms behind the interactions between insulin resistance and hyperandrogenism in the female liver remain largely unexplored. Using chronic treatment with insulin and/or human chorionic gonadotropin (hCG), we showed that all female rats with different treatments induced imbalance between de novo lipogenesis and mitochondrial β-oxidation via the Pparα/β–Srebp1/2–Acc1 axis, resulting in varying degrees of hepatic steatosis. Given the fact that hepatic lipid metabolism and inflammation are tightly linked processes, we found that hCG-induced hyperandrogenic rats had strongly aggravated hepatic inflammation. Further mechanistic investigations revealed that dysregulation of the IRS–PI3K–Akt signaling axis that integrated aberrant inflammatory, apoptotic and autophagic responses in the liver was strongly associated with hyperandrogenism itself or combined with insulin resistance. Additionally, we found that hCG-treated and insulin+hCG-induced rats developed visceral adipose tissue inflammation characterized by the presence of “crown like” structure and increased inflammatory gene expression. Because a more pronounced hepatic steatosis, inflammatory responses, and hepatocyte cell damage were observed in insulin+hCG-induced PCOS-like rats, our finding suggest that NAFLD seen in PCOS patients is dependent of hyperandrogenism and insulin resistance.
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Affiliation(s)
- Yuehui Zhang
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China.,Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Fanci Meng
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China
| | - Xiaoyan Sun
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China
| | - Xue Sun
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China
| | - Min Hu
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Peng Cui
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.,Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, 200032 Shanghai, China.,Institute of Integrative Medicine of Fudan University, 200032 Shanghai, China
| | - Edvin Vestin
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Xin Li
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.,Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 200011 Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 200011 Shanghai, China
| | - Wei Li
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China
| | - Xiao-Ke Wu
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, 150040 Harbin, China
| | - John-Olov Jansson
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Linus R Shao
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
| | - Håkan Billig
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
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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: 115] [Impact Index Per Article: 14.4] [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.
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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.
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Petta S, Ciresi A, Bianco J, Geraci V, Boemi R, Galvano L, Magliozzo F, Merlino G, Craxì A, Giordano C. Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS. PLoS One 2017; 12:e0186136. [PMID: 29161258 PMCID: PMC5697866 DOI: 10.1371/journal.pone.0186136] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 09/26/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis. METHODS We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism. RESULTS In the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (p<0.001), this association being maintained after adjusting for metabolic confounders (OR 3.73, 95% CI 1.74-8.02; P = 0.001). In PCOS patients, steatosis was independently linked to WC (OR 1.04, 95% CI 1.01-1.08; P = 0.006) and ISI Matsuda (OR 0.69, 95% CI 0.53-0.88; P = 0.004), not to free androgen index (OR 1.10, 95% CI 0.96-1.26; P = 0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, 95% CI 0.23-0.77, P = 0.005) and nonobese (OR 0.69, 95% CI 0.53-0.91, P = 0.009), patients, while FAI (OR 1.45, 95% CI 1.12-1.87; P = 0.004) emerged as an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p = 0.02) in nonobese and with lower ISI Matsuda (p = 0.04) in obese patients. CONCLUSIONS We found that PCOS is an independent risk factor for steatosis, and that, IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS.
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Affiliation(s)
- Salvatore Petta
- Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessandro Ciresi
- Section of Endocrinology, Diabetology and Metabolism, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Jessica Bianco
- Section of Endocrinology, Diabetology and Metabolism, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Vincenzo Geraci
- Section of Endocrinology, Diabetology and Metabolism, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Roberta Boemi
- Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | | | | | - Antonio Craxì
- Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Carla Giordano
- Section of Endocrinology, Diabetology and Metabolism, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
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Mehrabian F, Jahanmardi R. Nonalcoholic Fatty Liver Disease in a Sample of Iranian Women with Polycystic Ovary Syndrome. Int J Prev Med 2017; 8:79. [PMID: 29114377 PMCID: PMC5651659 DOI: 10.4103/ijpvm.ijpvm_305_16] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 07/09/2017] [Indexed: 01/10/2023] Open
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women in reproductive age that is associated with insulin resistance (IR) and metabolic abnormalities which are also a part of metabolic syndrome (Met S). This study was aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) women diagnosed with PCOS based on the Rotterdam criteria from January 2013 to June 2014. Methods: In this cross-sectional study, 75 women with PCOS and 75 healthy controls were enrolled. Anthropometric parameters, biochemical and hormonal investigation, were measured in all women. IR was calculated by homeostasis model assessment. Abdominal ultrasonography and biochemical tests were used to determine the NAFLD. Results: The level of triglyceride, cholesterol, low-density lipoprotein, aspartate aminotransferase, alkalin phosphatase, fasting insulin, and homeostatic model assessment index in women with PCOS were significantly higher than women without PCOS. High-density lipoprotein and alanine aminotransferase (ALT) in women with PCOS were significantly lower. The frequency of IR women with or without PCOS was 53.3% and 29.3%, respectively (P = 0.003). The frequency of Met S in women with PCOS was 33.3% and in other was 10.7% (P = 0.001). The prevalence of fatty liver in women with or without PCOS was 38.7% and 18.7%, respectively (0.008). In women with PCOS, body mass index (BMI) (odds ratio [OR] = 4.25; P = 0.046), ALT (OR = 1.62; P = 0.005), fasting insulin (OR = 1.32; P = 0.032), and IR (OR = 58.17; P = 0.025) were associated with a higher fatty liver. Conclusions: NAFLD is frequent in patients with PCOS with combination with other metabolic derangements. BMI, ALT, fasting insulin, and IR are the risk factors for high prevalence of NAFLD in women with PCOS.
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Affiliation(s)
- Ferdous Mehrabian
- Department of Obstetrics and Gynecology, Medical School, University of Medical Sciences, Isfahan, Iran
| | - Roya Jahanmardi
- Department of Obstetrics and Gynecology, Medical School, University of Medical Sciences, Isfahan, Iran
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47
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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: 34] [Impact Index Per Article: 4.3] [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.
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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
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Doycheva I, Watt KD, Alkhouri N. Nonalcoholic fatty liver disease in adolescents and young adults: The next frontier in the epidemic. Hepatology 2017; 65:2100-2109. [PMID: 28103626 DOI: 10.1002/hep.29068] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 01/07/2017] [Accepted: 01/13/2017] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a significant health burden in adolescents and young adults (AYAs) which has substantially risen in prevalence over the last decades. The occurrence of NAFLD parallels high rates of obesity and metabolic syndrome in this age group, with unhealthy lifestyle also playing an independent role. Genetic factors, sex, and ethnicity should be considered in a risk stratification model. NAFLD and nonalcoholic steatohepatitis (NASH) in AYAs often go unrecognized and, if untreated, can progress eventually to cirrhosis requiring liver transplantation (LT) before the age of 40. Recently, NASH has increased as an indication for LT in this age group. Important knowledge gaps include the feasibility of noninvasive diagnostic tests and imaging modalities as well as uncertainty about unique histological features and their predictive value. Future clinical trials focused on AYAs are needed to determine effectiveness of therapies. Tools for increasing awareness and prevention of NAFLD in AYAs are greatly needed. (Hepatology 2017;65:2100-2109).
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Affiliation(s)
- Iliana Doycheva
- Division of Gastroenterology and Hepatology, Medical University, Sofia, Bulgaria
| | - Kymberly D Watt
- Gastroenterology and Hepatology Department, Mayo Clinic, Rochester, MN
| | - Naim Alkhouri
- Department of Pediatric Gastroenterology, Cleveland Clinic Children's, Cleveland, OH.,Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH
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Cree-Green M, Rahat H, Newcomer BR, Bergman BC, Brown MS, Coe GV, Newnes L, Garcia-Reyes Y, Bacon S, Thurston JE, Pyle L, Scherzinger A, Nadeau KJ. Insulin Resistance, Hyperinsulinemia, and Mitochondria Dysfunction in Nonobese Girls With Polycystic Ovarian Syndrome. J Endocr Soc 2017; 1:931-944. [PMID: 29264544 PMCID: PMC5686696 DOI: 10.1210/js.2017-00192] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 05/26/2017] [Indexed: 01/28/2023] Open
Abstract
Objective: Obese girls with polycystic ovarian syndrome (PCOS) have decreased insulin sensitivity (IS), muscle mitochondrial dysfunction and increased liver fat, which may contribute to their increased risk for type 2 diabetes. Less is known regarding normal-weight girls with PCOS. Methods: Normal-weight girls with PCOS [n =18, age 15.9 ± 1.8 years, body mass index (BMI) percentile 68 ± 18] and normal-weight controls (NWC; n = 20; age 15.0 ± 2.1 years, BMI percentile 60 ± 21) were studied. Tissue-specific IS was assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers and a 2-hour oral glucose tolerance test (OGTT). Hepatic fat was determined using magnetic resonance imaging. Postexercise muscle mitochondrial function was assessed with 31P MR spectroscopy. Results: Both groups had similar demographics, anthropomorphics, physical attributes, habitual physical activity levels and fasting laboratory values, except for increased total testosterone and DHEAS in PCOS. Clamp-assessed peripheral IS was lower in PCOS (10.4 ± 2.4 mg/kg/min vs 12.7 ± 2.1; P = 0.024). The 120-minute OGTT insulin and glucose concentrations were higher in PCOS (114 IU/mL ± 26 vs 41 ± 25, P = <0.001 and 119 ± 22 mg/dL vs 85 ± 23, P = 0.01, respectively). Muscle mitochondrial ADP and phosphocreatine time constants were slower in PCOS. Despite a higher percentage liver fat in PCOS, hepatic IS was similar between groups, as was adipose IS. Conclusions: Normal-weight girls with PCOS have decreased peripheral IS and muscle mitochondrial dysfunction, abnormal glucose disposal, relative postprandial hyperinsulinemia, and increased hepatic fat compared to NWC. Despite a normal BMI, multiple aspects of metabolism appear altered in normal-weight girls with PCOS.
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Affiliation(s)
- Melanie Cree-Green
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.,Center for Women's Health Research, Aurora, Colorado 80045
| | - Haseeb Rahat
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Bradley R Newcomer
- Deptartment of Physics, James Madison University, Harrisburg, Virginia 22807
| | - Bryan C Bergman
- Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Mark S Brown
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Gregory V Coe
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Lindsey Newnes
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Yesenia Garcia-Reyes
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Samantha Bacon
- Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Jessica E Thurston
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045
| | - Laura Pyle
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado 80045.,Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Ann Scherzinger
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
| | - Kristen J Nadeau
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.,Center for Women's Health Research, Aurora, Colorado 80045
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Belan M, Pelletier C, Baillargeon JP. Alanine Aminotransferase Is a Marker of Lipotoxicity Consequences and Hyperandrogenemia in Women with Polycystic Ovary Syndrome. Metab Syndr Relat Disord 2017; 15:145-152. [DOI: 10.1089/met.2016.0119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Matea Belan
- Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
| | - Chloé Pelletier
- Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
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