Biomarkers in Endometriosis

In: How to Perform Ultrasonography in Endometriosis · 2018 · pp. 169–183 · doi:10.1007/978-3-319-71138-6_16 · W2897802217
book-chapter OA: closed CC0 ⤵ 1 in-corpus citation
Full text JSON View on OpenAlex View at publisher
AI-generated summary by claude@2026-06+body, 2026-06-12

Untreated endometriosis reduces quality of life and leads to depression, inability to work, sexual dysfunction, and missed motherhood opportunities.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-06 · read from full text

This paper reviews the role of biomarkers for noninvasive diagnosis of endometriosis, drawing on studies of blood and urinary markers (including CA-125, proteins, metabolomic profiles, microRNAs, and peptide patterns) as well as diagnostic test performance concepts and relevant systematic reviews/meta-analyses. It reports that numerous biomarker candidates have been explored across symptomatic populations, including analyses of diagnostic accuracy and the clinical utility framework for evaluating tests, while a major caveat is that there is still limited evidence supporting early treatment to prevent disease progression. The review also highlights unresolved issues in diagnosis and management, reflecting variability across marker types and study designs. This paper is centrally about endometriosis — it focuses specifically on biomarkers for the noninvasive diagnosis and diagnostic evaluation of endometriosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 16,191 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Although there are no data to show that early treatment of endometriosis prevents progression of the disease, untreated endometriosis is linked with reduced quality of life and outcomes such as depression, inability to work, sexual dysfunction, and missed opportunity for motherhood [1, 2]. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

References

Matsuzaki S, Canis M, Pouly JL, Rabischong B, Botchorishvili R, Mage G. Relationship between delay of surgical diagnosis and severity of disease in patients with symptomatic deep infiltrating endometriosis. Fertil Steril. 2006;86:1314–6. Gao X, Yeh YC, Outley J, Simon J, Botteman M, Spalding J. Health-related quality of life burden of women with endometriosis: a literature review. Curr Med Res Opin. 2006;22:1787–97. Ballard KD, Seaman HE, de Vries CS, Wright JT. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study - Part 1. BJOG. 2008;115(11):1382–91. Nnoaham KE, Hummelshoj L, Kennedy SH, Jenkinson C, Zondervan KT, World Endometriosis Research Foundation Women’s Health Symptom Survey Consortium. Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study. Fertil Steril. 2012;98:692–701. Eskenazi B, Warner M, Bonsignore L, Olive D, Samuels S, Vercellini P. Validation study of nonsurgical diagnosis of endometriosis. Fertil Steril. 2001;76(5):929–35. Wykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: a systematic quantitative review. BJOG. 2004;111:1204–12. Johnson NP, Hummelshoj L, Consortium WESM. Consensus on current management of endometriosis. Hum Reprod. 2013;28:1552–68. Vercellini P, Giudice LC, Evers JL, Abrao M. Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal. Hum Reprod. 2015;30:1996–2004. Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, Bush D, Kiesel L, Tamimi R, Sharpe-Timms KL, Rombauts L. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32:315–24. Nisenblat V, Bossuyt PMM, Shaikh R, Arora D, Farquhar C, Jordan V, Scheffers CS, Mol BWJ, Johnson N, Hull ML. Blood biomarkers for the non invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;(5):CD012179. doi:https://doi.org/10.1002/14651858. Bossuyt PMM, Reitsma JB, Linnet K, Moons KGM. Beyond diagnostic accuracy: the clinical utility of diagnostic tests. Clin Chem. 2012;58(12):1636–43. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364:1789–99. Burney RO. The genetics and biochemistry of endometriosis. Curr Opin Obstet Gynecol. 2013;25(4):280–6. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16:651–74. Liu E, Nisenblat V, Farquhar C, Fraser I, Bossuyt PMM, Johnson N, Hull ML. Urinary biomarkers for the non invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2015;(12):CD012019. doi: https://doi.org/10.1002/14651858. Mol BW, Bayram N, Lijmer JG, Wiegerinck MA, Bongers MY, van der Veen F, Bossuyt PM. The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril. 1998;70(6):1101–8. Hirsch M, Duffy J, Davis CJ, Nieves Plana M, Khan KS. Diagnostic accuracy of cancer antigen 125 for endometriosis: a systematic review and meta-analysis. BJOG. 2016;123(11):1761–8. Hirsch M, Duffy JMN, Deguara CS, Davis CJ, Khan KS. Diagnostic accuracy of Cancer Antigen 125 (CA125) for endometriosis in symptomatic women: a multi-center study. Eur J Obstet Gynecol Reprod Biol. 2017;210:102–7. Chen FP, Soong YK, Lee N, Lo SK. The use of serum CA-125 as a marker for endometriosis in patients with dysmenorrhea for monitoring therapy and for recurrence of endometriosis. Acta Obstet Gynecol Scand. 1998;77(6):665–70. Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K, Hornung D. Combination of CCR1 mRNA, MCP1, and CA125 measurements in peripheral blood as a diagnostic test for endometriosis. Reprod Sci. 2008;15(9):906–11. Lanzone A, Marana R, Muscatello R, Fulghesu AM, Dellacqua S, Caruso A, Mancuso S. Serum Ca-125 levels in the diagnosis and management of endometriosis. J Reprod Med. 1991;36(8):603–7. Vouk K, Hevir N, Ribic-Pucelj M, Haarpaintner G, Scherb H, Osredkar J, et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum Reprod. 2012;27(10):2955–65. Koninckx PR, Meuleman C, Oosterlynck D, Cornillie FJ. Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration. Fertil Steril. 1996;65(2):280–7. Vicente-Muñoz S, Morcillo I, Puchades-Carrasco L, Payá V, Pellicer A, Pineda-Lucena A. Pathophysiologic processes have an impact on the plasma metabolomic signature of endometriosis patients. Fertil Steril. 2016;106(7):1733–41. Letsiou S, Peterse DP, Fassbender A, Hendriks MM, van den Broek NJ, Berger R, O DF, Vanhie A, Vodolazkaia A, Van Langendonckt A, Donnez J, Harms AC, Vreeken RJ, Groothuis PG, Dolmans MM, Brenkman AB, D’Hooghe TM. Endometriosis is associated with aberrant metabolite profiles in plasma. Fertil Steril. 2017;107(3):699–706. Liu HY, Zheng YH, Zhang JZ, Leng JH, Sun DW, Liu ZF, et al. Establishment of endometriosis diagnostic model using plasma protein profiling. Chung-Hua Fu Chan Ko Tsa Chih [Chinese J Obstet Gynecol]. 2009;44(8):601–4. Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik A, Chittams J, et al. Proteomic analysis of serum yields six candidate proteins that are differentially regulated in a subset of women with endometriosis. Fertil Steril. 2010;93(7):2137–44. Fassbender A, Waelkens E, Verbeeck N, Kyama CM, Bokor A, Vodolazkaia A, et al. Proteomics analysis of plasma for early diagnosis of endometriosis. Obstet Gynecol. 2012;119(2 Pt 1):276–85. Wolfler MM, Schwamborn K, Otten D, Hornung D, Liu HY, Rath W. Mass spectrometry and serum pattern profiling for analyzing the individual risk for endometriosis: promising insights? Fertil Steril. 2009;91(6):2331–7. Jia SZ, Yang Y, Lang J, Sun P, Leng J. Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. 2013;28(2):322–30. Wang WT, Zhao YN, Han BW, Hong SJ, Chen YQ, Wang X, et al. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis [Study on polymorphism of human leukocyte antigen I in patients with endometriosis]. J Clin Endocrinol Metab. 2013;98(1):281–9. Cosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS. Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis. Fertil Steril. 2016;106(2):402–9. Cho S, Mutlu L, Grechukhina O, Taylor HS. Circulating microRNAs as potential biomarkers for endometriosis. Fertil Steril. 2015;103(5):1252–60. Wang L, Liu HY, Shi HH, Lang JH, Sun W. Urine peptide patterns for non-invasive diagnosis of endometriosis:a preliminary prospective study. Eur J Obstet Gynecol Reprod Biol. 2014;177:23–8. Vicente-Muñoz S, Morcillo I, Puchades-Carrasco L, Payá V, Pellicer A, Pineda-Lucena A. Nuclear magnetic resonance metabolomic profiling of urine provides a noninvasive alternative to the identification of biomarkers associated with endometriosis. Fertil Steril. 2015;104(5):1202–9. Burney RO, Talbi S, Hamilton AE, Kim CV, Nyegaard M, Nezhat CR, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148:3814–26. Kim JJ, Taylor HS, Lu Z, Ladhani O, Hastings JM, Jackson KS, et al. Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007;13:323–32. Brosens I, Brosens JJ, Benagiano G. The eutopic endometrium in endometriosis: are the changes of clinical significance? Reprod Biomed Online. 2012;24:496–502. Guo SW. Epigenetics of endometriosis. Mol Hum Reprod. 2009;15:587–607. Houshdaran S, Nezhat CR, Vo KC, Zelenko Z, Irwin JC, Giudice LC. Aberrant endometrial DNA methylome and associated gene expression in endometriosis. Biol Reprod. 2016;95(5):93. Bhusane K, Bhutada S, Chaudhari U, Savardekar L, Katkam R, Sachdeva G. Secrets of endometrial receptivity: some are hidden in uterine secretome. Am J Reprod Immunol. 2016;75:226–36. Gupta D, Hull ML, Fraser I, Miller L, Bossuyt PMM, Johnson N, Farquhar C, Nisenblat V. Endometrial biomarkers for the non invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;(4):CD012165. doi:https://doi.org/10.1002/14651858. Leslie C, Ma T, McElhinney B, Leake R, Stewart CJ. Is the detection of endometrial nerve fibers useful in the diagnosis of endometriosis? Int J Gynecol Pathol. 2013;32(2):149–55. Cetin C, Serdaroglu H, Tuzali S. The importance of endometrial nerve fibres and macrophage cell count in the diagnosis of endometriosis. Iran J Reprod Med. 2013;11(5):405–14. Nisenblat V, Bossuyt PMM, Farquhar C, Johnson N, Hull ML. Imaging modalities for the non invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;4:CD009591. doi:https://doi.org/10.1002/14651858. Marasinghe J, Senanayake H, Saravanabhava N, Arambepola C, Condous G, Greenwood P. History, pelvic examination findings and mobility of ovaries as a sonographic marker to detect pelvic adhesions with fixed ovaries. J Obstet Gynaecol Res. 2014;40(3):785–90. Guerriero S, Ajossa S, Paoletti AM, Mais V, Angiolucci M, Melis GB. Tumour marker and transvaginal ultrasonography in the diagnosis of endometrioma. Obstet Gynaecol. 1996;88(3):403–7. Bazot M, Lafont C, Rouzier R, Roseau G, Thomassin-Naggara I, Darai E. Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis. Fertil Steril. 2009;92(6):1825–33. Grasso RF, Di Giacomo V, Sedati P, Sizzi O, Florio G, Faiella E, et al. Diagnosis of deep infiltrating endometriosis: accuracy of magnetic resonance imaging and transvaginal 3D ultrasonography. Abdom Imaging. 2010;35(6):716–25. Guerriero S, Ajossa S, Gerada M, D'Aquila M, Piras B, Melis GB. “Tenderness-guided” transvaginal ultrasonography: a new method for the detection of deep endometriosis in patients with chronic pelvic pain. Fertil Steril. 2007;88:1293–7. Scarella AC, Devoto LC, Villarroel CQ, Inzunza NP, Quilodrán FR, Sovino HS. Transvaginal ultrasound for preoperative detection of deep endometriosis in patients with chronic pelvic pain [Ultrasonido transvaginal para la detección preoperatoria de endometriosis profunda en pacientes con dolor pélvico crónico]. Rev Chil Obstet Ginecol. 2013;78(2):114–8. Piessens S, Healey M, Maher P, Tsaltas J, Rombauts L. Can anyone screen for deep infiltrating endometriosis with transvaginal ultrasound? Aust N Z J Obstet Gynaecol. 2014;54(5):462–8. Hudelist G, English J, Thomas AE, Tinelli A, Singer CF, Keckstein J. Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2011;37(3):257–63. Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, Melis GB, Alcazar JL. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;46:534–45. Guerriero S, Ajossa S, Orozco R, Perniciano M, Jurado M, Melis GB, Alcazar JL. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2016;47(3):281–9. Hudelist G, Oberwinkler KH, Singer CF, Tuttlies F, Rauter G, Ritter O, et al. Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis. Hum Reprod. 2009;24(5):1018–24. Medeiros LR, Rosa MI, Silva BR, Reis ME, Simon CS, Dondossola ER, da Cunha Filho JS. Accuracy of magnetic resonance in deeply infiltrating endometriosis: a systematic review and meta-analysis. Arch Gynecol Obstet. 2015;291(3):611–21. Saba L, Sulcis R, Melis GB, de Cecco CN, Laghi A, Piga M, et al. Endometriosis: the role of magnetic resonance imaging. Acta Radiol. 2014, 56(3):355–67. Moore J, Copley S, Morris J, LIndsell D, Golding S, Kennedy S. A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol. 2002;20:630–4. Tammaa A, Fritzer N, Strunk G, Krell A, Salzer H, Hudelist G. Learning curve for the detection of pouch of Douglas obliteration and deep infiltrating endometriosis of the rectum. Hum Reprod. 2014;29(6):1199–204. Rutjes AWS, Reitsma JB, Vandenbroucke JP, Glas AS, Bossuyt PMM. Case–control and two-gate designs in diagnostic accuracy studies. Clin Chem. 2005;51(8):1335–41. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ. 2003;326(7379):41–4. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al., the QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529–36. Fassbender A, Rahmioglu N, Vitonis AF, Vigano P, Giudice LC, D’Hooghe TM, Hummelshoj L, Adamson GD, Becker CM, Missmer SA, Zondervan KT. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: IV. Tissue collection, processing, and storage in endometriosis research. Fertil Steril. 2014;102(5):1244–53. Rahmioglu N, Fassbender A, Vitonis AF, Tworoger SS, Hummelshoj L, D’Hooghe TM, Adamson GD, Giudice LC, Becker CM, Zondervan KR, Missmer SA. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil Steril. 2014;102(5):1233–43. Becker CM, Laufer MR, Stratton P, Hummelshoj L, Missmer SA, Zondervan KT, Adamson GD. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: I. Surgical phenotype data collection in endometriosis research. Fertil Steril. 2014;102(5):1213–22. Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis G, Hummelshoj L, Giudice L, Stratton P, Adamson GD, Becker CM, Zondervan KR, Missmer SA. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research. Fertil Steril. 2014;102(5):1223–32. Ahn SH, Singh V, Tayade C. Biomarkers in endometriosis: challenges and opportunities. Fertil Steril. 2017;107(3):523–32. Nisenblat V, Prentice L, Bossuyt PMM, Farquhar C, Hull ML, Johnson N. Combination of the non-invasive tests for the diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;7:CD012281.doi:https://doi.org/10.1002/14651858. Pusztai L, Hatzis C, Andre F. Nat Rev Clin Oncol. 2013;10:720–4. Horvath AR, Lord SJ, StJohn A, Sandberg S, Cobbaert CM, Lorenz S, Monaghan PJ, Verhagen-Kamerbeek WD, Ebert C, Bossuyt PM, Test Evaluation Working Group of the European Federation of Clinical Chemistry Laboratory Medicine. From biomarkers to medical tests: the changing landscape of test evaluation. Clin Chim Acta. 2014;427:49–57. Author information Authors and Affiliations Editor information Editors and Affiliations Rights and permissions Copyright information © 2018 Springer International Publishing AG, part of Springer Nature About this chapter Cite this chapter Nisenblat, V., Hull, M.L. (2018). Biomarkers in Endometriosis. In: Guerriero, S., Condous, G., Alcázar, J.L. (eds) How to Perform Ultrasonography in Endometriosis. Springer, Cham. https://doi.org/10.1007/978-3-319-71138-6_16 Download citation DOI: https://doi.org/10.1007/978-3-319-71138-6_16 Published: Publisher Name: Springer, Cham Print ISBN: 978-3-319-71137-9 Online ISBN: 978-3-319-71138-6 eBook Packages: MedicineMedicine (R0)

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (69)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK