Relationships between nonalcoholic fatty liver disease and polycystic ovary syndrome

Literature review

Authors

  • E.H. Manzhalii O.O. Bogomolets National Medical University; Ukrainian Liver Foundation; Global Longevity Institute; Clinic Verum Expert, Kyiv, Ukraine https://orcid.org/0000-0003-0920-4627
  • T.F. Tatarchuk SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”;State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-5498-4143
  • T.M. Tutchenko SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”; “Dila” Medical Laboratory, Kyiv, Ukraine https://orcid.org/0000-0002-3003-3650
  • N.V. Kosei SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0003-3085-3285
  • R.O. Mnevets ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv; SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Kyiv, Ukraine, Ukraine https://orcid.org/0000-0001-9614-5762

DOI:

https://doi.org/10.18370/2309-4117.2023.70.40-45

Keywords:

polycystic ovary syndrome, nonalcoholic fatty liver disease, hyperandrogenism, insulin resistance, sex steroid-binding globulin, fatty liver

Abstract

Polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) are two common non-infectious pathologies. Their frequency and medico-social significance have increased significantly over the past decades and reflect the effects of radical changes in human lifestyle on human health in a transgenerational aspect. Due to absence a complete understanding of the etiology and pathogenesis of PCOS and NAFLD, modern medicine still does not have etiopathogenetic methods of treating these frequent diseases. Considering epidemiological and pathogenetic data PCOS and NAFLD can be regarded as related pathologies, which creates the prospect of improving the effectiveness of their management if the joint approach to scientific research and implementation of their results in medical practice is applied.
The purpose of the review is to summarize the current scientific data on the common pathophysiological and clinical relationships between PCOS and NAFLD, which can contribute to improving the effectiveness management of both diseases.
Pathogenetic relationships between PCOS and NAFLD are bidirectional. According to current data, it seems possible to consider PCOS as a significant risk factor for the development of NAFLD in women of reproductive age both in the presence of excess weight and with normal body weight.
As is known, that liver is involved in the clearance of androgens by the formation of sex steroid-binding globulin, as well as in the inactivation of insulin. Disruption of these metabolic processes due to liver pathology can lead to the development or strengthening of biochemical and clinical hyperandrogenism and the development of hyperinsulinemia and insulin resistance (IR).
Conclusions. The presence of fatty liver and especially steatohepatitis deepens the hormonal disorders inherent in PCOS (primarily, an increase of free androgens, IR and ovulatory dysfunction), as well as potentiates and accelerates the development of cardiometabolic complications, including atherogenic dyslipidemia, dysglycemia, metabolic syndrome and cardiovascular complications. Early detection of NAFLD in women with PCOS, regardless of the presence of obesity, may improve the effectiveness of PCOS management and prevention of its cardiometabolic risks.

Author Biographies

E.H. Manzhalii, O.O. Bogomolets National Medical University; Ukrainian Liver Foundation; Global Longevity Institute; Clinic Verum Expert, Kyiv

Associate professor, Department of Propedeutics of Internal Medicine;

President;

CEO;

Chief of Hepatology department

T.F. Tatarchuk, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”;State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work, head of the Endocrine Gynecology Department;
Chief researcher, Department of Reproductive Health

T.M. Tutchenko, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”; “Dila” Medical Laboratory, Kyiv

PhD, senior researcher of the Endocrine Gynecology Department;
Department of Reproductive Health;
Scientific consultant of Medical Laboratory

N.V. Kosei, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; SSI “Center for Innovative Medical Technologies of the NAS of Ukraine”, Kyiv

MD, professor, chief researcher, Endocrine Gynecology Department;
Head of Department of Reproductive Health

R.O. Mnevets, ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv; SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Kyiv, Ukraine

Assistant, Department of Anatomy and Pathological Physiology;
Intern

References

  1. Bai J, Cui J, Shi F, Yu C. Global Epidemiological Patterns in the Burden of Main Non-Communicable Diseases, 1990–2019: Relationships With Socio-Demographic Index. Int J Public Health. 2023 Jan 16;68:1605502. DOI: 10.3389/ijph.2023.1605502
  2. Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep. 2018 Feb 26;20(2):12. DOI: 10.1007/s11906-018-0812-z
  3. Parker, Jim. Understanding the Pathogenesis of Polycystic Ovary Syndrome: A transgenerational evolutionary adaptation to lifestyle and the environment. J ACNEM. 2020; 39(4):18–26.
  4. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease – Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016 Jul;64(1): 73–84. DOI: 10.1002/hep.28431
  5. Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol. 2020 Apr 5;5:16. DOI: 10.21037/tgh.2019.09.08
  6. Vidal-Cevallos P, Mijangos-Trejo A, Uribe M, Tapia NC. The Interlink Between Metabolic-Associated Fatty Liver Disease and Polycystic Ovary Syndrome. Endocrinol Metab Clin North Am. 2023 Sep;52(3):533–45. DOI: 10.1016/j.ecl.2023.01.005.
  7. Salva-Pastor N, Chávez-Tapia NC, Uribe M, Nuño-Lámbarri N. Understanding the association of polycystic ovary syndrome and non-alcoholic fatty liver disease. J Steroid Biochem Mol Biol. 2019 Nov; 194: 105445. DOI: 10.1016/j.jsbmb.2019.105445
  8. Teede HJ, Tay CT, Laven JJE, et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Eur Journal Endocrinol. 2023 Aug 2;189(2):G43–G64. DOI: 10.1093/ejendo/lvad096.
  9. van der Ham K, Koster MPH, Velthuis BK, et al. Change in Androgenic Status and Cardiometabolic Profile of Middle-Aged Women with Polycystic Ovary Syndrome. J Clin Med. 2023 Aug 11;12(16):5226. DOI: 10.3390/jcm12165226
  10. Diamanti-Kandarakis E, Panidis D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin Endocrinol (Oxf). 2007 Nov;67(5): 735–42. DOI: 10.1111/j.1365-2265.2007.02954.x.
  11. Polak AM, Adamska A, Krentowska A, et al. Body composition, serum concentrations of androgens and insulin resistance in different polycystic ovary syndrome phenotypes. J Clin Med 2020 Mar 9;9(3):732. DOI: 10.3390/jcm9030732
  12. Gupta M, Yadav R, Mahey R, et al. Correlation of body mass index (BMI), anti-mullerian hormone (AMH), and insulin resistance among different polycystic ovary syndrome (PCOS) phenotypes-a cross-sectional study. Gynecol Endocrinol. 2019 Nov;35(11):970–3. DOI: 10.1080/09513590.2019.1613640
  13. Krentowska A, Kowalska I. Metabolic syndrome and its components in different phenotypes of polycystic ovary syndrome. Diabetes Metab Res Rev. 2022 Jan;38(1): e3464. DOI: 10.1002/dmrr.3464
  14. Williams T, Moore JB, Regehr J. Polycystic Ovary Syndrome: Common Questions and Answers. Am Fam Physician 2023 Mar;107(3):264–72.
  15. Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022 Sep;10(9):668–80. DOI: 10.1016/S2213-8587(22)00163-2
  16. Crespo RP, Bachega TASS, Mendonça BB, Gomes LG. An update of genetic basis of PCOS pathogenesis. Arch Endocrinol Metabol. 2018 Jun;62(3):352–361. DOI: 10.20945/2359-3997000000049
  17. Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol. 2023 Feb; 29(Suppl): S5–16. DOI: 10.3350/cmh.2022.0424
  18. Lonardo A, Arab JP, Arrese M. Perspectives on precision medicine approaches to NAFLD diagnosis and management. Adv Ther. 2021 May;38(5):2130–58. DOI: 10.1007/s12325-021-01690-1
  19. Dongiovanni P, Valenti L. Genetics of nonalcoholic fatty liver disease. Metabolism 2016 Aug;65(8): 1026-37. DOI: 10.1016/j.metabol.2015.08.018
  20. Wajsbrot NB, Leite NC, Salles GF, Villela-Nogueira CA. Non-alcoholic fatty liver disease and the impact of genetic, epigenetic and environmental factors in the offspring. World Journal Gastroenterol. 2022 Jul 7;28(25): 2890. DOI: 10.3748/wjg.v28.i25.2890
  21. Xie J, Huang H, Liu Z, et al. The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study. Hepatology. 2023 Mar 1;77(3):949-64. DOI: 10.1002/hep.32728
  22. Long MT, Noureddin M, Lim JK. AGA clinical practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review. Gastroenterology. 2022 Sep;163(3):764-74.e1. DOI: 10.1053/j.gastro.2022.06.023
  23. Patel AH, Peddu D, Amin S, et al. Nonalcoholic Fatty Liver Disease in Lean/Nonobese and Obese Individuals: A Comprehensive Review on Prevalence, Pathogenesis, Clinical Outcomes, and Treatment. J Clin Trans Hepatol 2023 Apr 28;11(2):502-15. DOI: 10.14218/JCTH.2022.00204
  24. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020 Jul;73(1):202-9. DOI: 10.1016/j.jhep.2020.03.039
  25. Eslam M, El-Serag HB, Francque S, et al. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol 2022 Oct;19(10):638-51. DOI: 10.1038/s41575-022-00635-5
  26. Manzhalii EG. Non-alcoholic fatty liver disease. New nomenclature. Review. Modern Gastroenterology. 2023;4(123):91-7. DOI:10.30978/MG-2023-4-91
  27. Lauschke VM. Practice guidance documents for the diagnosis and management of non-alcoholic fatty liver disease – recent updates and open questions. Hepatobiliary Surg Nutr. 2023 Oct 1;12(5):780–4. DOI: 10.21037/hbsn-23-376
  28. Yu O, Christ JP, Schulze-Rath R, et al. Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019. Am J Obstet Gynecol. 2023 Jul;229(1):39.e1–39.e12. DOI: 10.1016/j.ajog.2023.04.010
  29. Teng MLP, Ng CH, Huang DQ, et al. Global incidence and prevalence of nonalcoholic fatty liver disease. Clin Mol Hepatol. 2023 Feb;29(Suppl):S32–S42. DOI: 10.3350/cmh.2022.0365
  30. Huang T, Behary J, Zekry A. Non-alcoholic fatty liver disease: a review of epidemiology, risk factors, diagnosis and management. Intern Med Journal. 2020 Sep;50(9):1038–47. DOI: 10.1111/imj.14709
  31. Ge X, Zheng L, Wang M, et al. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990–2017: a population-based observational study. BMJ Open. 2020 Aug 3;10(8):e036663. DOI: 10.1136/bmjopen-2019-036663
  32. Selvakumar PKC, Kabbany MN, Lopez R, et al. Prevalence of suspected nonalcoholic fatty liver disease in lean adolescents in the United States. J Pediatr Gastroenterol Nutr. 2018 Jul;67(1):75–9. DOI: 10.1097/MPG.0000000000001974
  33. Ito T, Ishigami M, Zou B, et al. The epidemiology of NAFLD and lean NAFLD in Japan: A meta-analysis with individual and forecasting analysis, 1995–2040. Hepatol Int. 2021 Apr;15(2):366–379. DOI: 10.1007/s12072-021-10143-4
  34. Manzano-Nunez R, Santana-Dominguez M, Rivera-Esteban J, et al. Non-alcoholic fatty liver disease in patients with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression. J Clin Med. 2023 Jan 20;12(3):856. DOI: 10.3390/jcm12030856
  35. Cassar S, Misso ML, Hopkins WG, et al. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies. Hum Reprod. 2016 Nov;31(11):2619–31. DOI: 10.1093/humrep/dew243
  36. Stepto NK, Cassar S, Joham AE, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic–hyperinsulaemic clamp. Hum Reprod. 2013 Mar;28(3): 777–84. DOI: 10.1093/humrep/des463
  37. Hernández-Jiménez JL, Barrera D, Espinoza-Simón E, et al. Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance. Gynecol Endocrinol. 2022 Jan;38(1): 2–9. DOI: 10.1080/09513590.2021.2003326
  38. Rudnicka E, Suchta K, Grymowicz M, et al. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7):3789. DOI: 10.3390/ijms22073789
  39. Coskun EI, Omma T, Taskaldiran I, et al. Metabolic role of hepassocin in polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2023 Jun;27(11):5175–83. DOI: 10.26355/eurrev_202306_32635
  40. Genazzani AD, Andrea RG. Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance. touchREV Endocrinol. 2023 May;19(1):71–7. DOI: 10.17925/EE.2023.19.1.71
  41. Chen Y, Ma L, Ge Z, et al. Key genes associated with non-alcoholic fatty liver disease and polycystic ovary syndrome. Frontiers Mol Biosci. 2022 May 25:9:888194. DOI: 10.3389/fmolb.2022.888194
  42. Li M, Reynolds CM, Segovia SA, et al. Developmental programming of nonalcoholic fatty liver disease: the effect of early life nutrition on susceptibility and disease severity in later life. Biomed Res Int. 2015:2015:437107. DOI: 10.1155/2015/437107
  43. Lomas-Soria C, Reyes-Castro LA, Rodríguez-González GL, et al. Maternal obesity has sex-dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring. J Physiol. 2018 Oct;596(19):4611–28. DOI: 10.1113/JP276372.
  44. Ayonrinde OT., Oddy WH, Adams LA, et al. Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents. J Hepatol. 2017 Sep;67(3):568–76.
  45. Simó R, Barbosa-Desongles A, Sáez-Lopez C, et al. Molecular Mechanism of TNFα-Induced Down-Regulation of SHBG Expression. Mol Endocrinol. 2012 Mar;26(3):438–46. DOI: 10.1210/me.2011-1321
  46. Song MJ, Choi JY. Androgen dysfunction in non-alcoholic fatty liver disease: Role of sex hormone binding globulin. Front Endocrinol (Lausanne). 2022 Nov 22;13:1053709. DOI: 10.3389/fendo.2022.1053709.
  47. Qu X, Donnelly R. Sex hormone-binding globulin (SHBG) as an early biomarker and therapeutic target in polycystic ovary syndrome. Int J Mol Sci. 2020 Nov 1;21(21):8191. DOI: 10.3390/ijms21218191
  48. Xing C, Zhang J, Zhao H, He B. Effect of sex hormone-binding globulin on polycystic ovary syndrome: mechanisms, manifestations, genetics, and treatment. Int J Womens Health. 2022 Feb 2;14:91–105.DOI: 10.2147/IJWH.S344542.
  49. Xargay-Torrent S, Carreras-Badosa G, Borrat-Padrosa S, et al. Circulating sex hormone binding globulin: An integrating biomarker for an adverse cardio-metabolic profile in obese pregnant women. PloS One. 2018 Oct 15;13(10):e0205592. DOI: 10.1371/journal.pone.0205592.
  50. Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest. 2000 Feb;105:311–20. DOI: 10.1172/JCI7535.
  51. Rice S, Christoforidis N, Gadd C, et al. Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. Hum Reprod. 2005 Feb;20:373–81. DOI: 10.1093/humrep/deh609
  52. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012 Dec;33(6):981–1030. DOI: 10.1210/er.2011-1034.
  53. Xu F, Liu R, Cao X. Hyperandrogenism stimulates inflammation and promote apoptosis of cumulus cells. Cell Mol Biol (Noisy-le-grand). 2017 Oct 31;63(10):64–8. DOI: 10.14715/cmb/2017.63.10.10
  54. Baranova Ancha, Tran TP, Afendy A, et al. Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS). J Transl Med. 2013 May 31:11:133. DOI: 10.1186/1479-5876-11-133
  55. Sarkar M, Terrault N, Chan W, et al. Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis. Liver Int. 2020 Feb;40(2):355–9. DOI: 10.1111/liv.14279
  56. Fouda S, Jeeyavudeen MS, Pappachan JM, et al. Pathobiology of Metabolic-Associated Fatty Liver Disease. Endocrinol Metab Clin North Am. 2023 Sep;52(3):405–16. DOI: 10.1016/j.ecl.2023.01.001

Published

2023-12-29

How to Cite

Manzhalii, E., Tatarchuk, T., Tutchenko, T., Kosei, N., & Mnevets, R. (2023). Relationships between nonalcoholic fatty liver disease and polycystic ovary syndrome: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (70), 40–45. https://doi.org/10.18370/2309-4117.2023.70.40-45

Issue

Section

Interdisciplinary problems