Could ELABELA be a Protective Biomarker in Patients with Abnormal Uterine Bleeding?

Abstract

Aim: Abnormal uterine bleeding (AUB) is a health problem characterized by various symptoms such as heavy and prolonged menstrual bleeding, affecting approximately 30% of female patients both physiologically and psychologically. The objective of this study was to assess serum Elabela (ELA) concentrations in women aged 18 and above diagnosed with functional AUB, and to compare these concentrations with those of healthy women. Material and Method: This prospective case-control study was performed from August 18, 2022 to December 30, 2022. This was a cross-sectional study including 50 women who applied to the gynecology service of Malatya Turgut Özal Training and Research Hospital with complaints of AUB and 50 women without AUB who underwent gynecological examination. The presence of AUB in patients was determined based on clinical examination conducted by a gynecologist and medical records. Demographic and clinical characteristics were recorded. Serum ELA levels were determined by commercial ELISA kit. Results: Serum ELA levels was significantly lower in patients with AUB (581.54±272.25 pg/mL) compared to the healthy group (744.55±300.31 pg/mL, p=0.005). In this study, ELA in patients with AUB showed 98% sensitivity and 80% specificity with a cut off value of 411.41 pg/mL (area under the curve [AUC], 68.1%; p=0.002). Conclusion: Serum ELA levels in patients with AUB were significantly lower than in healthy women. These results show that ELA is a good predictor of the pathophysiological process of AUB.

Keywords

• Elabela
• abnormal uterine bleeding
• PALM-COEIN

Kaynakça

1. Mutakha GS, Mwaliko E, Kirwa P. Clinical bleeding patterns and management techniques of abnormal uterine bleeding at a teaching and referral hospital in Western Kenya. Plos One. 2020;15:e0243166.
2. Livingstone M, Frase IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update. 2002;8:60-7.
3. Whitaker L, Critchley HOD. Abnormal uterine bleeding. Best Pract & Res Clin Obstet and Gynaecol. 2016; 34:54-65.
4. Matteson KA, Boardman LA, Munro MG, Clark MA. Abnormal uterine bleeding: a review of patient-based outcome measures. Fertil and Steril. 2009;92:205-16.
5. Crawford NM, Pritchard DA, Herring AH, Steiner AZ. Prospective evaluation of the impact of intermenstrual bleeding on natural fertility. Fertil and Steril. 2016;105:1294-300.
6. Albers JR, Hull SK, Wesley RM. Anormal uterine bleeding. Am Fam Physician. 2004;69:1915-26.
7. Wouk N, Helton M. Abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2019;99:435-43.
8. Marnach ML, Laughlin-Tammaso SK. Evaluation and management of abnormal uterine bleeding. Mayo Clin Proc. 2019;94:326-35.

9. Lebduska E, Beshear D, Spataro BM. Abnormal uterine bleeding. Med Clin Of North Am. 2023;107:235-46.
10. Chodankar R, Critchley HOD. Biomarkers in abnormal uterine bleeding. Biol Reprod. 2019;101:1155-66.
11. Wang Z, Yu D, Wang MQ, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems. Sci Rep. 2015;5:8170.
12. Hanssens S, Marousez L, Pecheux O, et al. Maternal obesity reduces apelin level in cord blood without altering the placental apelin/elabela-APJ system. Placenta. 2022;128:112-5.
13. Xu J, Chen L, Jiang Z, et al. Biological functions of elabela, a novel endogeneous ligand of APJ reseptor. J Cell Physiol. 2018;233:6472-82.
14. Chen Z, Luo X, Liu M, et al. Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway. J Cell Biochem. 2023;124:586-605.
15. Mansour D, Hofmann A, Gemzell-Danielsson K. A review of clinical guidelines on the management of iron deficiency and iron-deficiency anemia in women with heavy menstrual bleeding. Adv Ther. 2021;38:201-25.
16. Munro MG, Mast AE, Powers JM, et al. The relationship between heavy menstrual bleeding, iron deficiency, and iron deficiency anemia. Am J Obstet Gynecol. 2023;229:1-9.
17. Karatoprak C, Sekerci A, Karaaslan T, et al. Could vitamin K1 defiency be the problem in iron deficiency and/or anemia in premenopausal women?. Bezmialem Sci. 2022;10:139-43.
18. Sowers MR, Zheng H, Jannausch ML, et al. Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause. J Clin Endocrinol Metab. 2010;95:2155-62.
19. Guo Y, Zhao M, Bo T, et al. Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol. Cell Res. 2019;29:151-66.
20. Serana M, Tagliazucchi D. Bioactive peptides in human health and disease. Int J Mol Sci. 2023;24:5837.
21. Respekta N, Pich K, Dawid M, et al. The apelinergic system: apelin, elabela, and APJ action on cell apoptosis: anti-apoptotic or pro-apoptotic effect?. Cells. 2023;12:150.
22. Xu P, Kong L, Tao C, et al. Elabela-APJ axis attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal ferroptosis. Free Radic Biol Med. 2023;196:171-86.
23. Monastero R, Magro D, Venezia M, et al. A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: the elabela/apela/toddler peptide. Ageing Res Rev. 2023;91:102076.
24. Masoumi J, Jafarzadeh A, Khorramdelazad H, et al. Role of Apelin/APJ axis in cancer development and progression. Adv Med Sci. 2020;65:202-13.
25. Bongrani A, Mellouk N, Rame C, et al. Ovarian expression of adipokines in polycystic ovary syndrome: a role for chemerin, omentin, and apelin in follicular growth arrest and ovulatory dysfunction?. Int J Mol Sci. 2019;20:3778.
26. Coquerel D, Chagnon F, Sainsily X, et al. Elabela improves cardio-renal outcome in fatal experimental septic shock. Crit Care Med. 2017;45:1139-48.
27. Critchley HOD, Maybin JA. Molecular and cellular causes of abnormal uterine bleeding of endometrial origin. Semin Reprod Med. 2011;29:400-9.
28. Kacar E, Ercan Z, Serhatlioglu I, et al. The effects of apelin on myometrium contractions in pregnant rats. Cell Mol Biol. 2018;64:74-9.
29. Hehir MP, Morrison JJ. The adipokine apelin and human uterine contractility. Am J Obstet Gynecol. 2012;206:359.e1-359.e3595.
30. Mercati F, Scocco P, Maranesi M, et al. Apelin system detection in the reproductive apparatus of ewes grazing on semi-natural pasture. Theriogenology. 2019;139:156-66.