Skip to main content

Advertisement

SpringerLink
Log in

What Do Higher Alanine Aminotransferase Levels Mean in Premature Ovarian Insufficiency?

  • Reproductive Endocrinology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The objective of this study was to investigate the relationship between alanine aminotransferase and related biochemical parameters and potential risk factors in women with premature ovarian insufficiency (POI). This is a retrospective cohort study with 126 POI patients (including subclinical POI, n= 27) and 130 healthy controls who visited our clinic between April 2021 to November 2022. Associations were investigated by multiple linear regression, Person correlation analysis, the Kruskal-Wallis test, Mann-Whitney U test, and the independent t-test. When compared to controls, analysis of POI patients showed that body mass index (BMI), uric acid (UA) and urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), monocyte/lymphocyte ratio, monocyte count (MONO), neutrophil count (NEUT), follicle-stimulating hormone (FSH), luteinizing hormone, and neutrophil/lymphocyte ratio (NLR) were significantly higher, while estradiol (E2), the lymphocyte count and the AST/ALT ratio were lower (P < 0.05). According to linear correlation, it was clear that BMI, FSH, white blood cell count (WBC), NEUT, MONO, UA, AST, and NLR were positively associated with ALT (r = 0.215, 0.388, 0.195, 0.187, 0.184, 0.605, 0.819, and 0.189, respectively, all P < 0.05) while E2 was negatively associated with ALT (r = −0.278, P < 0.05). In addition, multiple linear regression revealed a significant, independent, and positive correlation between AST, FSH, and ALT (B =1.403 and 0.069, respectively, P < 0.05). Analysis revealed that the levels of ALT were significantly higher in POI patients. In addition, BMI, FSH, UA, AST, MONO, NLR, NEUT, and WBC were positively associated with ALT in POI patients. E2 was negatively associated with ALT. Multiple linear regression revealed an independent and positive correlation between AST, FSH, and ALT. In addition, there was also a risk of liver function damage in women with POI and subclinical POI. If patients were diagnosed with POI, early examination and corresponding intervention will be required to effectively prevent the further development of liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

References

  1. Giri R, Vincent AJ. Prevalence and risk factors of premature ovarian insufficiency/early menopause. Semin Reprod Med. 2020;38(4-05):237–46.

    PubMed  Google Scholar 

  2. Albright F, Smith PH, Fraser R. A syndrome characterized by primary ovarian insufficiency and decreased stature: report of 11 cases with a digression on hormonal control of axillary and pubic hair. Am J Med Sci. 1942;204(5):625–48.

    Article  Google Scholar 

  3. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M, Anderson R, Bartlett J, Braat D, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.

    Article  Google Scholar 

  4. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clin Genet. 2017;91(2):183–98.

    Article  CAS  PubMed  Google Scholar 

  6. Podfigurna A, Stellmach A, Szeliga A, Czyzyk A, Meczekalski B. Metabolic profile of patients with premature ovarian insufficiency. J Clin Med. 2018;7(10):374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kunicki M, Rudnicka E, Skórska J, Calik-Ksepka AI, Smolarczyk R. Insulin resistance indexes in women with premature ovarian insufficiency - a pilot study. Ginekol Pol. 2018;89(7):364–9.

    Article  PubMed  Google Scholar 

  8. Hashimoto E, Taniai M, Tokushige K. Characteristics and diagnosis of NAFLD/NASH. J Gastroenterol Hepatol. 2013;28(Suppl 4):64–70.

    Article  CAS  PubMed  Google Scholar 

  9. Yang H, Li D, Song X, Liu F, Wang X, Ma Q, et al. Joint associations of serum uric acid and ALT with NAFLD in elderly men and women: a Chinese cross-sectional study. J Transl Med. 2018;16(1):285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Goldberg D, Ditah IC, Saeian K, Lalehzari M, Aronsohn A, Gorospe EC, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(5):1090–9.e1.

    Article  PubMed  Google Scholar 

  11. Friedman SL, Ratziu V, Harrison SA, Abdelmalek MF, Aithal GP, Caballeria J, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018;67(5):1754–67.

    Article  CAS  PubMed  Google Scholar 

  12. Fröhlich E, Wahl R. Insight into potential interactions of thyroid hormones, sex hormones and their stimulating hormones in the development of non-alcoholic fatty liver disease. Metabolites. 2022;12(8):718.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Patlolla AK, Kumari SA, Tchounwou PB. A comparison of poly-ethylene-glycol-coated and uncoated gold nanoparticle-mediated hepatotoxicity and oxidative stress in Sprague Dawley rats. Int J Nanomed. 2019;14:639–47.

    Article  CAS  Google Scholar 

  14. Long MT, Pedley A, Colantonio LD, Massaro JM, Hoffmann U, Muntner P, et al. Development and validation of the Framingham steatosis index to identify persons with hepatic steatosis. Clin Gastroenterol Hepatol. 2016;14(8):1172–80.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cho JY, Jeong JY, Sohn W. Risk of metabolic syndrome in participants within the normal range of alanine aminotransferase: a population-based nationwide study. PLoS One. 2020;15(4):e0231485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gawrieh S, Wilson LA, Cummings OW, Clark JM, Loomba R, Hameed B, et al. Histologic findings of advanced fibrosis and cirrhosis in patients with nonalcoholic fatty liver disease who have normal aminotransferase levels. Am J Gastroenterol. 2019;114(10):1626–35.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liu XM, Chan HC, Ding GL, Cai J, Song Y, Wang TT, et al. FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca(2+)/CREB pathway. Aging Cell. 2015;14(3):409–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Song Y, Wang ES, Xing LL, Shi S, Qu F, Zhang D, et al. Follicle-stimulating hormone induces postmenopausal dyslipidemia through inhibiting hepatic cholesterol metabolism. J Clin Endocrinol Metab. 2016;101(1):254–63.

    Article  CAS  PubMed  Google Scholar 

  19. Sun Z, Miller RA, Patel RT, Chen J, Dhir R, Wang H, et al. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med. 2012;18(6):934–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yu YM, Zhou BH, Yang YL, Guo CX, Zhao J, Wang HW. Estrogen deficiency aggravates fluoride-induced liver damage and lipid metabolism disorder in rats. Biol Trace Elem Res. 2022;200(6):2767–76.

    Article  CAS  PubMed  Google Scholar 

  21. Yan H, Yang W, Zhou F, Li X, Pan Q, Shen Z, et al. Estrogen improves insulin sensitivity and suppresses gluconeogenesis via the transcription factor foxo1. Diabetes. 2019;68(2):291–304.

    Article  CAS  PubMed  Google Scholar 

  22. Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv Ther. 2017;34(6):1291–326.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sanverdi I, Kilicci C, Cogendez E, Abide Yayla C, Ozkaya E. Utility of complete blood count parameters to detect premature ovarian insufficiency in cases with oligomenorrhea/amenorrhea. J Clin Lab Anal. 2018;32(5):e22372.

    Article  PubMed  Google Scholar 

  24. Chuang SJ, Sung YC, Chen CY, et al. Can match-mimicking intermittent practice be used as a simulatory training mode of competition using olympic time frame in elite Taekwondo athletes? Front Physiol. 2019 Mar;20(10):244.

    Article  Google Scholar 

  25. Wang SC, Chou JF, Strong VE, Brennan MF, Capanu M, Coit DG. Pretreatment neutrophil to lymphocyte ratio independently predicts disease-specific survival in resectable gastroesophageal junction and gastric adenocarcinoma. Ann Surg. 2016;263(2):292–7.

    Article  PubMed  Google Scholar 

  26. Zavatta A, Parisi F, Mandò C, et al. Role of inflammaging on the reproductive function and pregnancy. Clin Rev Allergy Immunol. 2023;64(2):145–60.

    Article  PubMed  Google Scholar 

  27. Huang Y, Hu C, Ye H, Luo R, Fu X, Li X, et al. Inflamm-aging: a new mechanism affecting premature ovarian insufficiency. J Immunol Res. 2019;2019:8069898.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yan F, Zhao Q, Li Y, Zheng Z, Kong X, Shu C, et al. The role of oxidative stress in ovarian aging: a review. J Ovarian Res. 2022;15(1):100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Xu Z, Mu S, Liao X, Fan R, Gao W, Sun Y, et al. Estrogen protects against liver damage in sepsis through inhibiting oxidative stress mediated activation of pyroptosis signaling pathway. PLoS One. 2020;15(10):e0239659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Robeva R, Mladenović D, Vesković M, Hrnčić D, Bjekić-Macut J, Stanojlović O, et al. The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause. Maturitas. 2021;151:22–30.

    Article  CAS  PubMed  Google Scholar 

  31. Shen HH, Yang CY, Kung CW, et al. Raloxifene inhibits adipose tissue inflammation and adipogenesis through Wnt regulation in ovariectomized rats and 3 T3-L1 cells. J Biomed Sci. 2019;26(1):62.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chen S, Guo X, Yu S, et al. Association between serum uric acid and elevated alanine aminotransferase in the general population. Int J Environ Res Public Health. 2016;13(9):841.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Molla NH, Kathak RR, Sumon AH, Barman Z, Mou AD, Hasan A, et al. Assessment of the relationship between serum uric acid levels and liver enzymes activity in Bangladeshi adults. Sci Rep. 2021;11(1):20114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu HH, Cao YX, Sun D, et al. Impact of non-alcoholic fatty liver disease on cardiovascular outcomes in patients with stable coronary artery disease: a matched case-control study. Clin Transl Gastroenterol. 2019 Feb;10(2):e00011.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ochocki JD, Khare S, Hess M, Ackerman D, Qiu B, Daisak JI, et al. Arginase 2 suppresses renal carcinoma progression via biosynthetic cofactor pyridoxal phosphate depletion and increased polyamine toxicity. Cell Metab. 2018;27(6):1263–80.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Especially, we would like to express our appreciation to professor Yuquan Zhang for his valuable support in designing the study and the medical statistician Hanchun Xue for statistical advice.

Funding

This study is supported by the multi-center clinical collaborative research project of the Affiliated Hospital of Nantong University (No. LCYJ-B09) and the medical research program of Jiangsu Provincial Health Commission, China (No. Z2022069).

Author information

Author notes

  1. Weina Wang, Xi Cheng, and Jinhan Yao contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China

    Weina Wang, Chenglu Li, Xia Wang, You Zhang, Siyi Chen & Yuquan Zhang

  2. Medical School of Nantong University, Nantong, China

    Weina Wang, Xi Cheng, Jinhan Yao, Hanchun Xue, Chenglu Li, You Zhang & Siyi Chen

Authors
  1. Weina Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinhan Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hanchun Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chenglu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. You Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Siyi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuquan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Weina Wang (W-nW) came up with the idea. Data collection was performed by W-nW, Xia Wang (X-W), Chenglu Li (C-lL), You Zhang (Y-Z), and Siyi Chen (S-yC). Hanchun Xue (H-cX) was responsible for the data quality control. Data analysis was done by W-nW and H-cX. The first draft of the manuscript was written by W-nW. Y-qZ, Jinhan Yao (J-hY), and Xi Cheng (X-C) participated in the design of the study and revision of the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuquan Zhang.

Ethics declarations

Ethics Approval

This study was approved by the Ethics Review Board of the Affiliated Hospital of Nantong University, Nantong, Jiangsu, China on October 16, 2018(2018-K057). We passed the amendment ethics review on August 30, 2021 (2018-K057-02). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, W., Cheng, X., Yao, J. et al. What Do Higher Alanine Aminotransferase Levels Mean in Premature Ovarian Insufficiency?. Reprod. Sci. 31, 469–479 (2024). https://doi.org/10.1007/s43032-023-01303-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-023-01303-y

Keywords

Search

Navigation