Use of Neutrophil-to-Lymphocyte Ratio Combined With CA-125 to Distinguish Endometriomas From Other Benign Ovarian Cysts

Purpose The objective of this study was to evaluate the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR) compared to CA-125 in patients with endometriomas.

This study was designed as a retrospective comparative study. A total of 807 women who underwent surgery due to benign ovarian cysts between January 2008 and January 2013 were included in the study. The NLR and CA-125 levels were assessed separately and together, with a receiver–operating characteristic curve analysis for the diagnosis of endometriomas.

The mean serum levels of NLR, CA-125, and combined markers were significantly higher in the study group (all P < .001). According to the highest Youden index, the cutoff values were found to be 23.7 IU/mL for CA-125 at 75% sensitivity and 81% specificity and 1.89 for NLR at 70% sensitivity and 74% specificity. The cutoff value for the combined marker was 41.0 with 80% sensitivity and 82% specificity. There was a positive correlation between NLR and CA-125 (P < .001). Neutrophil-to-lymphocyte ratio was also positively correlated with the endometriosis score (P < .001).

Although NLR is a simple and easily applicable marker, CA-125 is superior for differentiating endometriomas from other benign ovarian cysts. The combination of these 2 markers improves diagnostic accuracy. Similar content being viewed by others

Witz CA, Burns WN. Endometriosis and infertility: is there a cause and effect relationships? Gynecol Obstet Invest. 2002; 53(suppl 1):2–11. Tokmak A, Ugur M, Tonguc E, Var T, Moraloğlu O, Ozaksit G. The value of urocortin and Ca-125 in the diagnosis of endometrioma. Arch Gynecol Obstet. 2011;283(5):1075–1079. Eskenazi B, Warner M, Bonsignore L, Olive D, Samuels S, Vercellini P. Validation study of nonsurgical diagnosis of endometriosis. Fertil Steril. 2001;76(5):929–935. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674. Hirsch M, Davis CJ. Preoperative assessment and diagnosis of endometriosis: are we any closer? Curr Opin Obstet Gynecol. 2015;27(4):284–290. Nisolle M. Ovarian endometriosis and peritoneal endometriosis: are they different entities from a fertility perspective? Curr Opin Obstet Gynecol. 2002;14(3):283–288. Nisolle M, Casanas-Roux F, Donnez J. Immunohistochemical analysis of proliferative activity and steroid receptor expression in peritoneal and ovarian endometriosis. Fertil Steril. 1997; 68(5):912–919. Redwine DB. Ovarian endometriosis: a marker for more extensive pelvic and intestinal disease. Fertil Steril. 1999;72(2):310–315. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789–1799. Nezhat F, Nezhat C, Allan CJ, Metzger DA, Sears DL. Clinical and histologic classification of endometriomas. Implications for a mechanism of pathogenesis. J Reprod Med. 1992;37(9): 77176. Dupuis CS, Kim YH. Ultrasonography of adnexal causes of acute pelvic pain in pre-menopausal non-pregnant women. Ultrasonography. 2015;34(4):258–267. doi:10.14366/usg.15013. Sanchez AM, Vigano P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M. The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary. Hum Reprod Update. 2014;20(2):217–230. Sayan CD, Özakşit MG, Sarıkaya E, Eryılmaz ÖG, Mollamahmutoğlu L, Deveer R. Serum interleukin-8, CA-125 levels, neutrophil-to-lymphocyte ratios, and combined markers in the diagnosis of endometriosis. Turkish J Med Sci. 2013;43(3): 417–423. Agic A, Xu H, Finas D, Banz C, Diedrich K, Hornung D. Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest. 2006;62(3):139–147. Vodolazkaia A, El-Aalamat Y, Popovic D, et al. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod. 2012;27(9):2698–2711. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637–653. Cho S, Cho H, Nam A, et al. Neutrophil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis. Fertil Steril. 2008;90(6):2073–2079. Mol BW, Bayram N, Lijmer JG, et al. The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril. 1998;70(6):1101–1108. Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002;17(2):42–431. Oosterlynck DJ, Meuleman C, Lacquet FA, Waer M, Koninckx PR. Flow cytometry analysis of lymphocyte subpopulations in peritoneal fluid of women with endometriosis. Am J Reprod Immunol. 1994;31(1):25–31. Klentzeris LD, Bulmer JN, Liu DT, Morrison L. Endometrial leukocyte subpopulations in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 1995;63(1):41–47. Iwasaki K, Makino T, Maruyama T, Matsubayashi H, Nozawa S, Yokokura T. Leukocyte subpopulations and natural killer activity in endometriosis. Int J Fertil Menopausal Stud. 1999;38(4): 229–234. Gómez-Torres MJ, Acién P, Campos A, Velasco I. Embryotoxicity of peritoneal fluid in women with endometriosis. Its relation with cytokines and lymphocyte populations. Hum Reprod. 2002; 17(3):777–781. Gallinelli A, Chiossi G, Giannella L, Marsella T, Genazzani AD, Volpe A. Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets. Gynecol Endocrinol. 2004;18(3):144–151. Gagné D, Rivard M, Pagé M, Shazand K, Hugo P, Gosselin D. Blood leukocyte subsets are modulated in patients with endometriosis. Fertil Steril. 2003;80(1):43–53. D’Hooghe TM, Nugent N, Cuneo S, et al. Recombinant human TNF binding protein (r-hTBP-1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo-and drug-controlled study. Biol Reprod. 2006;74(1):131–136. D’Hooghe TM, Hill JA, Oosterlynck DJ, Koninckx PR, Bambra CS. Effect of endometriosis on white blood cell subpopulations in peripheral blood and peritoneal fluid of baboons. Hum Reprod. 1996;11(8):1736–1740. Kim SK, Park JY, Jee BC, Suh CS, Kim SH. Association of the neutrophil-to-lymphocyte ratio and CA 125 with the endometriosis score. Clin Exp Reprod Med. 2014;41(4):151–157. Yavuzcan A, Çağlar M, Üstün Y, et al. Evaluation of mean platelet volume, neutrophil/ lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma. J Turk Ger Gynecol Assoc. 2013;14(4):210–215. Yang H, Lang JH, Zhu L, Wang S, Sha GH, Zhang Y. Diagnostic value of the neutrophil-to-lymphocyte ratio and the combination of serum CA-125 for stages III and IV endometriosis. Chin Med J (Engl). 2013;126(11):2011–2014. Polak G, Barczynski B, Bednarek W, et al. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis. Ginekol Pol. 2015;86(6):414–418. Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54(2): 82–87. Salmeri FM, Lagana AS, Sofo V, et al. Behavior of tumor necrosis factor-α and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages. Reprod Sci. 2015;22(2):165–172. Xue P, Kanai M, Mori Y, et al. Neutrophil-to-lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients. Cancer Med. 2014;3(2):406–415. Kurdoglu Z, Gursoy R, Kurdoglu M, Erdem M, Erdem O, Erdem A. Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis. Fertil Steril. 2009;92(5):1761–1763. Xavier P, Beires J, Belo L, et al. Are we employing the most effective CA 125 and CA 19-9 cut-off values to detect endometriosis? Eur J Obstet Gynecol Reprod Biol. 2005; 123(2):254–255. Chmaj-Wierzchowska K, Kampioni M, Wilczak M, Opala T. Do inflammatory factors play a significant role in etiopathogenesis of endometrial cysts? Part 1. Ann Agric Environ Med. 2013;20(4): 854–858. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Tokmak, A., Yildirim, G., Öztaş, E. et al. Use of Neutrophil-to-Lymphocyte Ratio Combined With CA-125 to Distinguish Endometriomas From Other Benign Ovarian Cysts. Reprod. Sci. 23, 795–802 (2016). https://doi.org/10.1177/1933719115620494 Published: Issue date: DOI: https://doi.org/10.1177/1933719115620494