Features of correction of metabolic disorders in women with polycystic ovary syndrome

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2024.73.60-66

Keywords:

polycystic ovary syndrome, liver dysfunction, hyperandrogenemia, insulin resistance, obesity, liver-ovary axis, metabolic mechanisms, hyperglycemia, infertility

Abstract

Background. A significant proportion of couples worldwide suffer from infertility associated with polycystic ovary syndrome (PCOS). PCOS is characterized by increased androgen synthesis in the theca cells of the ovaries, hyperandrogenemia and ovarian dysfunction in women. Most of the clinical symptoms and altered levels of blood biomarkers in PCOS patients point to metabolic dysregulation and adaptive changes as key underlying mechanisms of disease development. Since the liver is the metabolic center of the body and participates in steroid-hormonal detoxification, pathological changes in it can contribute to endocrine disorders through the liver-ovary axis. Of particular interest is hyperglycemia, changes in secretory proteins of the liver and insulin sensitivity, which affect the maturation of ovarian follicles and can potentially lead to female infertility.
Objective of the review: to provide an understanding of the new metabolic mechanisms underlying PCOS, which lead to the disease and its exacerbation, as well as to summarize therapeutic approaches to the correction of PCOS complications, in particular, liver function disorders using the drug Hepatomunil.
Analysis of literary data. This review presents the relationship and underlying mechanistic basis between PCOS and metabolic disorders in women by summarizing the main pathologic features of the disease. Most symptoms of PCOS are associated with insulin resistance, type II diabetes, decreased levels of sex hormone-binding globulin, increased levels of alanine aminotransferase and aspartate aminotransferase, which may indicate liver dysfunction. The metabolic profile and function of the ovaries can be affected by any pathological changes in the levels of systemic metabolism and/or in peripheral organs, in particular the liver, which serves as the metabolic center of the body, mediating its effects through the liver-ovary axis.
Conclusions. Despite the lack of a clear protocol for the correction of liver function disorders and non-alcoholic fatty liver disease in PCOS patients, lifestyle modification should be the basis. Drugs that improve metabolism, as well as hepatoprotectors with immunomodulatory properties (the drug Hepatomunil) may have positive prospects for use.

Author Biographies

O.V. Bulavenko, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, head of the Department of Obstetrics and Gynecology No. 2

D.G. Konkov, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Department of Obstetrics and Gynecology No. 1

O.A. Taran, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Department of Obstetrics and Gynecology No. 1

O.V. Furman, National Pirogov Memorial Medical University, Vinnytsia

PhD, associate professor, Department of Obstetrics and Gynecology No. 2

V.V. Klivak, National Pirogov Memorial Medical University, Vinnytsia

PhD, associate professor, Department of Obstetrics and Gynecology No. 2

References

  1. Teede HJ, Tay CT, Laven JJE, et al. International PCOS Network. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Eur J Endocrinol. 2023 Sep 18;108(10):43-64. DOI: 10.1093/ejendo/lvad096
  2. Forslund M, Melin J, Piltonen T. New update of the international PCOS guideline-Focus on evidence-based medicine in the treatment of PCOS. Acta Obstet Gynecol Scand. 2024 Aug;103(8):1682. DOI: 10.1111/aogs.14892
  3. Franik G, Bizoń A, Szynkaruk-Matusiak M, et al. The association between 24-hour ambulatory blood pressure measurement and selected biochemical and anthropometric parameters in women with polycystic ovary syndrome. Eur. Rev. Med. Pharmacol. Sci. 2021 Jun;25(11): 3947–3954. DOI: 10.26355/eurrev_202106_26035
  4. Kim JJ, Hwang KR, Oh SH, et al. Prevalence of insulin resistance in Korean women with polycystic ovary syndrome according to various homeostasis model assessment for insulin resistance cutoff values. Fertil. Steril 2019 Nov;112(5): 959–966. DOI: 10.1016/j.fertnstert.2019.06.035
  5. Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics. Metabolism. 2019 Mar;92: 108–120. DOI: 10.1016/j.metabol.2018.11.002
  6. Varma HS, Tirupati S, Pradeep TVS, et al. Insulin resistance and hyperandrogenemia independently predict nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Diabetes Metab Syndr. 2019 Mar-Apr;13(2): 1065–1069. DOI: 10.1016/j.dsx.2018.12.020
  7. Parveen S, Khan S, Ahsan H, et al. Fat mass and Obesity Associated (FTO) gene and polycystic ovary syndrome: Insight into pathogenesis and association with insulin resistance. Human Nutrition & Metabolism. 2022. Dec 30:200174. DOI: 10.1016/j.hnm.2022.200174
  8. Gnanadass AS, Prabhu DY, Gopalakrishnan VA. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): An update. Arch. Gynecol. Obstet 2021. Mar;303(3): 631–643. DOI: 10.1007/s00404-020-05951-2
  9. Rocha ALL, Faria LC, Guimaraes TCM, et al. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: Systematic review and meta-analysis. J. Endocrinol. Investig. 2017. Dec;40(12): 1279–1288. DOI: 10.1007/s40618-017-0708-9
  10. Mehrabian F, Jahanmardi R. Nonalcoholic Fatty Liver Disease in a Sample of Iranian Women with Polycystic Ovary Syndrome. Int J Prev Med. 2017 Oct 5:8:79. DOI: 10.4103/ijpvm.IJPVM_305_16
  11. Velez LM, Seldin M, Motta AB. Inflammation and reproductive function in women with polycystic ovary syndrome. Biol Reprod. 2021 Jun 4;104(6):1205–1217. DOI: 10.1093/biolre/ioab050
  12. Hoeger K.M, Dokras A, Piltonen T. Update on PCOS: Consequences, challenges, and guiding treatment. J. Clin. Endocrinol. Metab. 2021 Mar 8;106(3):1071–1083. DOI: 10.1210/clinem/dgaa839
  13. Dallel S, Tauveron I, Brugnon F, et al. Liver X receptors: A possible link between lipid disorders and female infertility. Int. J. Mol. Sci. 2018 Jul 25;19(8):2177. DOI: 10.3390/ijms19082177
  14. Dybciak P, Humeniuk E, Raczkiewicz et al. Anxiety and Depression in Women with Polycystic Ovary Syndrome. Medicina (Kaunas). 2022 Jul 16;58(7):942. DOI: 10.3390/medicina58070942
  15. McCartney C.R, Campbell R.E. Abnormal GnRH Pulsatility in Polycystic Ovary Syndrome: recent Insights. Curr Opin Endocr Metab Res. 2020 Jun:12:78–84. DOI: 10.1016/j.coemr.2020.04.005
  16. Li T, Zhang T, Cui T, et al. Involvement of endogenous testosterone in hepatic steatosis in women with polycystic ovarian syndrome. J Steroid Biochem Mol Biol. 2020 Nov:204:105752. DOI: 10.1016/j.jsbmb.2020.105752
  17. Seidu T, McWhorter P, Myer J, et al. DHT causes liver steatosis via transcriptional regulation of SCAP in normal weight female mice. J Endocrinol. 2021 28;250(2):49–65. DOI:10.1530/JOE-21-0040
  18. Jahromi BN, Borzou N, Parsanezhad ME, et al. Associations of insulin resistance, sex hormonebinding globulin, triglyceride, and hormonal profiles in polycystic ovary syndrome: a cross-sectional study. Int J Reprod Biomed. 2021 16;19(7):653–662. DOI: 10.18502/ijrm.v19i7.9476
  19. Fujii H, Kawada N, Japan Study Group Of Nafld Jsg-Nafld. The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2020 May 29;21(11):3863. DOI: 10.3390/ijms21113863
  20. Zhang Y, Meng F, Sun X, et al. Hyperandrogenism and insulin resistance contribute to hepatic steatosis and inflammation in female rat liver. Oncotarget. 2018 Feb 9;9(26):18180–18197. DOI: 10.18632/oncotarget.2447
  21. Barber, T.M, Kyrou, I, Randeva, H.S, Weickert, M.O. Mechanisms of Insulin Resistance at the Crossroad of Obesity with Associated Metabolic Abnormalities and Cognitive Dysfunction. Int J Mol Sci. 2021 Jan 7;22(2):546. DOI: 10.3390/ijms22020546
  22. Biernacka-Bartnik, A, Kocełak, P, Owczarek, A.J, et al. Prediction of Insulin Resistance and Impaired Fasting Glucose Based on Sex Hormone-Binding Globulin (SHBG) Levels in Polycystic Ovary Syndrome. Int J Endocrinol. 2022 Jan 31:2022:6498768. DOI: 10.1155/2022/6498768
  23. Song X, Shen Q, Fan L, et al. Dehydroepiandrosterone-induced activation of mTORC1 and inhibition of autophagy contribute to skeletal muscle insulin resistance in a mouse model of polycystic ovary syndrome. Oncotarget. 2018 Jan 12;9(15):11905–11921. DOI: 10.18632/oncotarget.24190
  24. Barber, T.M, Hanson, P, Weickert, M.O, Franks, S. Obesity and Polycystic Ovary Syndrome: implications for Pathogenesis and Novel Management Strategies. Clin Med Insights Reprod Health. 2019 Sep 9:13:1179558119874042. DOI: 10.1177/1179558119874042
  25. Shengir M, Chen T, Guadagno E, et al. Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: a systematic review and meta-analysis. JGH Open. 2021 Feb 25;5(4):434–445. DOI: 10.1002/jgh3.12512
  26. Polyzos SA, Kountouras J, Mantzoros C.S. Adipose tissue, obesity and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017 Jun;42(2):92–108. DOI: 10.23736/S0391-1977.16.02563-3
  27. Khan, M.S, Lee, C, Kim, S.G. Non-alcoholic fatty liver disease and liver secretome. Arch. Pharm. Res. 2022 Dec;45(12):938–963. DOI: 10.1007/s12272-022-01419-w
  28. Appari M, Channon KM, McNeill E. Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes. Antioxid Redox Signal. 2018 Jul 20;29(3):297–312. DOI: 10.1089/ars.2017.7060
  29. Krishnan, A, Muthusami, S, Periyasamy, L, et al. Effect of DHT-Induced Hyperandrogenism on the Pro- Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology. Medicina (Kaunas). 2020 Feb 27;56(3):100. DOI: 10.3390/medicina56030100
  30. Rudnicka E, Kunicki M, Suchta,K, et al. Inflammatory Markers in Women with Polycystic Ovary Syndrome. Biomed Res Int. 2020 Mar 4:2020:4092470. DOI: 10.1155/2020/4092470
  31. Shorakae, S, Ranasinha, S, Abell, S, et al. Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS. Clin Endocrinol. 2018 Nov;89(5):628–633. DOI:10.1111/cen.13808
  32. Rostamtabar, M, Esmaeilzadeh, S, Tourani, M, et al. Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome. J Cell Physiol. 2021 Feb;236(2):824–838. DOI: 10.1002/jcp.29912
  33. Eiras MC, Pinheiro DP, Romcy KAM, et al. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022 Mar;29(3):680-694. DOI: 10.1007/s43032-021-00516-3
  34. Bruni V, Capozzi A, Lello S. The role of genetics, epigenetics and lifestyle in polycystic ovary syndrome development: the state of the art. Reproductive Sciences. 2022 Mar;29(3):668– 679. DOI: 10.1007/s43032-021-00515-4
  35. Duică F, Dănilă CA, Boboc AE, et al. Impact of increased oxidative stress on cardiovascular diseases in women with polycystic ovary syndrome. Frontiers in Endocrinology. 2021 Feb 18:12:614679:614679. DOI: 10.3389/fendo.2021.614679
  36. Abudawood M, Tabassum H, Alanazi AH, et al. Antioxidant status in relation to heavy metals induced oxidative stress in patients with polycystic ovarian syndrome (PCOS). Scientific Reports. 2023 25;11(1):22935. DOI: 10.1038/s41598-021-02120-6
  37. Zainab EM, Sayran SS. Role of Oxidative Strees and Antioxidants in Obese and non-obese women with Polycystic Ovary Syndrome. International Journal of Medical Science and Clinical Research Studies. 2023 3;4:709–712. DOI: 10.47191/ijmscrs/v3-i4-24
  38. Shengir M, Krishnamurthy S, Ghali P, et al. Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome. World J Gastroenterol. 2020 Nov 28;26(44):7046–7060. DOI: 10.3748/wjg.v26.i44.7046
  39. Zhang J, Hu J, Zhang C, et al. Analyses of risk factors for polycystic ovary syndrome complicated with non-alcoholic fatty liver disease. Exp Ther Med. 2018 May;15(5):4259–4264. DOI: 10.3892/etm.2018.5932
  40. Cui P, Hu W, Ma T, et al. Long-term androgen excess induces insulin resistance and non-alcoholic fatty liver disease in PCOS-like rats. J Steroid Biochem Mol Biol. 2021 Apr:208: 105829. DOI: 10.1016/j.jsbmb.2021.105829
  41. Polyzos, S.A, Kountouras, J, Mantzoros, C.S. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019 Mar:92:82–97. DOI: 10.1016/j.metabol.2018.11.014
  42. Cheng X, H, B. Clinical and biochemical potential of antioxidants in treating polycystic ovary syndrome. International Journal of Women’s Health. 2022 Apr 1:14:467–479. DOI: 10.2147/IJWH.S345853
  43. Chen JH, Lin X, Bu C, Zhang X. Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutrition and Metabolism. 2018 Oct 10:72. DOI: 10.1186/s12986-018-0306-7
  44. Podfigurna A, Meczekalski B, Petraglia F, Luisi S. Clinical, hormonal and metabolic parameters in women with PCOS with different combined oral contraceptives (containing chlormadinone acetate versus drospirenone). J Endocrinol Invest. 2020 Apr;43(4):483-492. DOI: 10.1007/s40618-019-01133-3
  45. Guang HJ, Li F, Shi J. Letrozole for patients with polycystic ovary syndrome: A retrospective study. Medicine (Baltimore). 2018 Nov;97(44):e13038. DOI: 10.1097/MD.0000000000013038

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Published

2024-10-18

How to Cite

Bulavenko, O., Konkov, D., Taran, O., Furman, O., & Klivak, V. (2024). Features of correction of metabolic disorders in women with polycystic ovary syndrome: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (73), 60–66. https://doi.org/10.18370/2309-4117.2024.73.60-66

Issue

No. 73 (2024)

Section

Interdisciplinary problems

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