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Copeptin is associated with the severity of endometriosis

Archives of Gynecology and Obstetrics volume 290, pages 75–82 (2014)Cite this article

Abstract

Purpose

Endometriosis is defined as the presence of endometrial glands and stroma in ectopic locations and may be associated with local and systemic inflammatory processes. Copeptin is elevated in acute and chronic inflammation conditions. The aim of the present study was to determine whether serum copeptin levels were altered in women with endometriosis and played a role in the pathophysiology of the disease.

Methods

A total of 86 women were recruited for this case–control study. 50 patients with surgically proven endometriosis were included, while 36 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with American Society of Reproductive Medicine revised classification. Two subgroups were formed by combining patients with minimal and mild disease and with moderate and severe disease (Stage 1–2, stage 3–4; respectively). Levels of copeptin, tumor markers (CA-125, CA-19-9, CA-15-3) and C-reactive protein in serum were measured.

Results

Serum copeptin, CA-125, CA-15-3 and CA-19-9 levels were higher in the endometriosis group (p: 0.002; 0.001; 0.017; 0.015; respectively). Copeptin and CA-19-9 levels were significantly higher in stage 3–4 group as compared to stage 1–2 group (p: 0.004; 0.036 respectively). Serum copeptin levels were positively correlated with stage of the disease and size of endometriomas. ROC analysis revealed that CA-125 had the highest AUC for predicting endometriosis (0.938; 95 % confidence interval 0.882–0.993; p: 0.001).

Conclusions

Serum copeptin levels were significantly higher in patients with endometriosis as compared to healthy controls. Moreover, severity of the disease was correlated with serum copeptin levels.

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References

  1. Eskenazi B, Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin N Am 24(2):235–258

    Article  CAS  Google Scholar 

  2. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A (2002) Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 17(2):426–431

    Article  CAS  PubMed  Google Scholar 

  3. Cho SH, Oh YJ, Nam A, Kim HY, Park JH, Kim JH, Park KH, Cho DJ, Lee BS (2007) Evaluation of serum and urinary angiogenic factors in patients with endometriosis. Am J Reprod Immunol 58(6):497–504. doi:10.1111/j.1600-0897.2007.00535.x

    Article  CAS  PubMed  Google Scholar 

  4. Darai E, Detchev R, Hugol D, Quang NT (2003) Serum and cyst fluid levels of interleukin (IL)-6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumours. Hum Reprod 18(8):1681–1685

    Article  CAS  PubMed  Google Scholar 

  5. Ulukus M, Ulukus EC, Seval Y, Zheng W, Arici A (2005) Expression of interleukin-8 receptors in endometriosis. Hum Reprod 20(3):794–801. doi:10.1093/humrep/deh675

    Article  CAS  PubMed  Google Scholar 

  6. Potocki M, Reichlin T, Thalmann S, Zellweger C, Twerenbold R, Reiter M, Steuer S, Bassetti S, Drexler B, Stelzig C, Freese M, Winkler K, Haaf P, Balmelli C, Hochholzer W, Osswald S, Mueller C (2012) Diagnostic and prognostic impact of copeptin and high-sensitivity cardiac troponin T in patients with pre-existing coronary artery disease and suspected acute myocardial infarction. Heart 98(7):558–565. doi:10.1136/heartjnl-2011-301269

    Article  CAS  PubMed  Google Scholar 

  7. Tentzeris I, Jarai R, Farhan S, Perkmann T, Schwarz MA, Jakl G, Wojta J, Huber K (2011) Complementary role of copeptin and high-sensitivity troponin in predicting outcome in patients with stable chronic heart failure. Eur J Heart Fail 13(7):726–733. doi:10.1093/eurjhf/hfr049

    Article  CAS  PubMed  Google Scholar 

  8. Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, Muller K, Meckel S, Gass A, Kappos L, Steck AJ, Engelter ST, Muller B, Christ-Crain M (2009) Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol 66(6):799–808. doi:10.1002/ana.21783

    Article  CAS  PubMed  Google Scholar 

  9. Enhorning S, Wang TJ, Nilsson PM, Almgren P, Hedblad B, Berglund G, Struck J, Morgenthaler NG, Bergmann A, Lindholm E, Groop L, Lyssenko V, Orho-Melander M, Newton-Cheh C, Melander O (2010) Plasma copeptin and the risk of diabetes mellitus. Circulation 121(19):2102–2108. doi:10.1161/CIRCULATIONAHA.109.909663

    Article  PubMed Central  PubMed  Google Scholar 

  10. Zhu XD, Chen JS, Zhou F, Liu QC, Chen G, Zhang JM (2011) Detection of copeptin in peripheral blood of patients with aneurysmal subarachnoid hemorrhage. Crit Care 15(6):R288. doi:10.1186/cc10575

    Article  PubMed Central  PubMed  Google Scholar 

  11. Morgenthaler NG, Struck J, Alonso C, Bergmann A (2006) Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52(1):112–119. doi:10.1373/clinchem.2005.060038

    Article  CAS  PubMed  Google Scholar 

  12. Chapron C, Souza C, Borghese B, Lafay-Pillet MC, Santulli P, Bijaoui G, Goffinet F, de Ziegler D (2011) Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis. Hum Reprod 26(8):2028–2035. doi:10.1093/humrep/der156

    Article  CAS  PubMed  Google Scholar 

  13. Chapron C, Lafay-Pillet MC, Monceau E, Borghese B, Ngo C, Souza C, de Ziegler D (2011) Questioning patients about their adolescent history can identify markers associated with deep infiltrating endometriosis. Fertil Steril 95(3):877–881. doi:10.1016/j.fertnstert.2010.10.027

    Article  PubMed  Google Scholar 

  14. (1997) Revised American Society for reproductive medicine classification of endometriosis: 1996. Fertil Steril 67(5):817-821

  15. Dousset B, Leconte M, Borghese B, Millischer AE, Roseau G, Arkwright S, Chapron C (2010) Complete surgery for low rectal endometriosis: long-term results of a 100-case prospective study. Ann Surg 251(5):887–895. doi:10.1097/SLA.0b013e3181d9722d

    Article  PubMed  Google Scholar 

  16. Fauconnier A, Chapron C, Dubuisson JB, Vieira M, Dousset B, Breart G (2002) Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil Steril 78(4):719–726

    Article  PubMed  Google Scholar 

  17. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J (2005) Fertility, family planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth. Vital Health Stat 23(25):1–160

    Google Scholar 

  18. Gazvani R, Templeton A (2002) Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 123(2):217–226

    Article  CAS  PubMed  Google Scholar 

  19. Harada T, Iwabe T, Terakawa N (2001) Role of cytokines in endometriosis. Fertil Steril 76(1):1–10

    Article  CAS  PubMed  Google Scholar 

  20. Oral E, Olive DL, Arici A (1996) The peritoneal environment in endometriosis. Hum Reprod Update 2(5):385–398

    Article  CAS  PubMed  Google Scholar 

  21. Matarese G, De Placido G, Nikas Y, Alviggi C (2003) Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med 9(5):223–228

    Article  CAS  PubMed  Google Scholar 

  22. Ramadori G, VanDamme J, Rieder H, Meyer zum Buschenfelde KH (1988) Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. Eur J Immunol 18(8):1259–1264. doi:10.1002/eji.1830180817

    Article  CAS  PubMed  Google Scholar 

  23. Chikanza IC, Grossman AB (1996) Neuroendocrine immune responses to inflammation: the concept of the neuroendocrine immune loop. Baillieres Clin Rheumatol 10(2):199–225

    Article  CAS  PubMed  Google Scholar 

  24. Tsagarakis S, Holly JM, Rees LH, Besser GM, Grossman A (1988) Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor-41 from the rat hypothalamus in vitro. Endocrinology 123(4):1962–1969

    Article  CAS  PubMed  Google Scholar 

  25. Fontano A, Weber E, Dayer J (1984) Synthesis of interleukin-l/endogenous pyrogen in the brain of endotoxin-treated mice: a step in fever induction. J Immunol 133:1696–1701

    Google Scholar 

  26. Krueger JM, Walter J, Dinarello CA, Wolff SM, Chedid L (1984) Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol 246(6 Pt 2):R994–R999

    CAS  PubMed  Google Scholar 

  27. Chikanza IC, Chrousos G, Panayi GS (1992) Abnormal neuroendocrine immune communications in patients with rheumatoid arthritis. Eur J Clin Invest 22(10):635–637

    Article  CAS  PubMed  Google Scholar 

  28. Morgenthaler NG, Struck J, Jochberger S, Dunser MW (2008) Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab 19(2):43–49. doi:10.1016/j.tem.2007.11.001

    Article  CAS  PubMed  Google Scholar 

  29. Szinnai G, Morgenthaler NG, Berneis K, Struck J, Muller B, Keller U, Christ-Crain M (2007) Changes in plasma copeptin, the c-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects. J Clin Endocrinol Metab 92(10):3973–3978. doi:10.1210/jc.2007-0232

    Article  CAS  PubMed  Google Scholar 

  30. Katan M, Morgenthaler N, Widmer I, Puder JJ, Konig C, Muller B, Christ-Crain M (2008) Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuro Endocrinol Lett 29(3):341–346

    CAS  PubMed  Google Scholar 

  31. Lima AP, Moura MD, Rosa e Silva AA (2006) Prolactin and cortisol levels in women with endometriosis. Braz J Med Biol Res 39(8):1121–1127

    Article  CAS  PubMed  Google Scholar 

  32. Monsivais D, Bray JD, Su E, Pavone ME, Dyson MT, Navarro A, Kakinuma T, Bulun SE (2012) Activated glucocorticoid and eicosanoid pathways in endometriosis. Fertil Steril 98(1):117–125. doi:10.1016/j.fertnstert.2012.03.030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Stolz D, Christ-Crain M, Morgenthaler NG, Leuppi J, Miedinger D, Bingisser R, Muller C, Struck J, Muller B, Tamm M (2007) Copeptin, C-reactive protein, and procalcitonin as prognostic biomarkers in acute exacerbation of COPD. Chest 131(4):1058–1067. doi:10.1378/chest.06-2336

    Article  CAS  PubMed  Google Scholar 

  34. Zulfikaroglu E, Islimye M, Tonguc EA, Payasli A, Isman F, Var T, Danisman N (2011) Circulating levels of copeptin, a novel biomarker in pre-eclampsia. J Obstet Gynaecol Res 37(9):1198–1202. doi:10.1111/j.1447-0756.2010.01498.x

    Article  CAS  PubMed  Google Scholar 

  35. Abrao MS, Podgaec S, Filho BM, Ramos LO, Pinotti JA, de Oliveira RM (1997) The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod 12(11):2523–2527

    Article  CAS  PubMed  Google Scholar 

  36. Xavier P, Belo L, Beires J, Rebelo I, Martinez-de-Oliveira J, Lunet N, Barros H (2006) Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet 273(4):227–231. doi:10.1007/s00404-005-0080-4

    Article  CAS  PubMed  Google Scholar 

  37. Lermann J, Mueller A, Korber F, Oppelt P, Beckmann MW, Dittrich R, Renner SP (2010) Evaluation of high-sensitivity C-reactive protein in comparison with C-reactive protein as biochemical serum markers in women with endometriosis. Fertil Steril 93(7):2125–2129. doi:10.1016/j.fertnstert.2009.01.072

    Article  CAS  PubMed  Google Scholar 

  38. Mihalyi A, Gevaert O, Kyama CM, Simsa P, Pochet N, De Smet F, De Moor B, Meuleman C, Billen J, Blanckaert N, Vodolazkaia A, Fulop V, D’Hooghe TM (2010) Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod 25(3):654–664. doi:10.1093/humrep/dep425

    Article  CAS  PubMed  Google Scholar 

  39. Somigliana E, Vigano P, Tirelli AS, Felicetta I, Torresani E, Vignali M, Di Blasio AM (2004) Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. Hum Reprod 19(8):1871–1876. doi:10.1093/humrep/deh312

    Article  CAS  PubMed  Google Scholar 

  40. Kurdoglu Z, Gursoy R, Kurdoglu M, Erdem M, Erdem O, Erdem A (2009) Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis. Fertil Steril 92(5):1761–1763. doi:10.1016/j.fertnstert.2009.05.022

    Article  CAS  PubMed  Google Scholar 

  41. Mol BW, Bayram N, Lijmer JG, Wiegerinck MA, Bongers MY, van der Veen F, Bossuyt PM (1998) The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril 70(6):1101–1108

    Article  CAS  PubMed  Google Scholar 

  42. Matalliotakis IM, Goumenou AG, Mulayim N, Karkavitsas N, Koumantakis EE (2005) High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid between patients with and without endometriosis. Arch Gynecol Obstet 271(1):40–45. doi:10.1007/s00404-004-0645-7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey

    Abdullah Tuten, Metehan Imamoglu, Abdullah Serdar Acikgoz, Nevin Yilmaz & Mahmut Oncul

  2. Department of Biochemistry, Istanbul University Cerrahpasa School of Medicine, Fatih, Istanbul, 34015, Turkey

    Mine Kucur & Zeynep Ozturk

  3. Department of Obstetrics and Gynecology, Near East University School of Medicine, Nicosia, Cyprus

    Baris Kaya

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  1. Abdullah Tuten
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Tuten, A., Kucur, M., Imamoglu, M. et al. Copeptin is associated with the severity of endometriosis. Arch Gynecol Obstet 290, 75–82 (2014). https://doi.org/10.1007/s00404-014-3163-2

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  • DOI: https://doi.org/10.1007/s00404-014-3163-2

Keywords

  • Copeptin
  • Endometriosis
  • Inflammation
  • Stage