Gastroenterologist Primer: Endometriosis for Gastroenterologists

Background and Aim A comprehensive understanding of endometriosis and its common gastrointestinal presentations are critical for gastroenterologists to ensure appropriate and timely screening and diagnosis. Endometriosis is a common inflammatory disease that frequently presents with gastrointestinal symptoms overlapping with irritable bowel syndrome (IBS) and other gastrointestinal disorders. Many endometriosis patients first present to a gastroenterologist or generalist, which may prolong the time to diagnosis and appropriate care.

and Results This review describes the current literature on endometriosis presentation, overlap with gastrointestinal conditions, and standard diagnostic and treatment options for gastroenterologists to consider. For appropriate and swift treatment, gastroenterologists must consider an endometriosis diagnosis in females of menstruating age presenting with pain, bloating, altered stools, and non-gastrointestinal symptoms and refer patients for further evaluation. Similar content being viewed by others

Sinaii N, Plumb K, Cotton L et al. Differences in characteristics among 1,000 women with endometriosis based on extent of disease. Fertil Steril. 2008;89:538–545. https://doi.org/10.1016/j.fertnstert.2007.03.069. Ek M, Roth B, Ekström P, Valentin L, Bengtsson M, Ohlsson B. Gastrointestinal symptoms among endometriosis patients—A case-cohort study. BMC Womens Health. 2015;15:59. https://doi.org/10.1186/s12905-015-0213-2. Fuldeore MJ, Soliman AM. Prevalence and Symptomatic Burden of Diagnosed Endometriosis in the United States: National Estimates from a Cross-Sectional Survey of 59,411 Women. Gynecol Obstet Invest. 2017;82:453–461. https://doi.org/10.1159/000452660. Luscombe GM, Markham R, Judio M, Grigoriu A, Fraser IS. Abdominal bloating: an under-recognized endometriosis symptom. J Obstet Gynaecol Can JOGC J Obstet Gynecol Can JOGC. 2009;31:1159–1171. https://doi.org/10.1016/s1701-2163(16)34377-8. Pugsley Z, Ballard K. Management of endometriosis in general practice: the pathway to diagnosis. Br J Gen Pract. 2007;57:470–476. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382:1244–1256. https://doi.org/10.1056/NEJMra1810764. Ballard KD, Seaman HE, Vries CD, Wright JT. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case–control study—Part 1. BJOG Int J Obstet Gynaecol. 2008;115:1382–1391. https://doi.org/10.1111/j.1471-0528.2008.01878.x. Shafrir AL, Farland LV, Shah DK et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1–15. https://doi.org/10.1016/j.bpobgyn.2018.06.001. Ghiasi M, Kulkarni MT, Missmer SA. Is Endometriosis More Common and More Severe Than It Was 30 Years Ago? J Minim Invasive Gynecol. 2020;27:452–461. https://doi.org/10.1016/j.jmig.2019.11.018. Soliman AM, Yang H, Du EX, Kelley C, Winkel C. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod. 2016;31:712–722. https://doi.org/10.1093/humrep/dev335. Nezhat C, Li A, Falik R et al. Bowel endometriosis: diagnosis and management. Am J Obstet Gynecol. 2018;218:549–562. https://doi.org/10.1016/j.ajog.2017.09.023. Schink M, Konturek PC, Herbert SL, et al. Different nutrient intake and prevalence of gastrointestinal comorbidities in women with endometriosis. J Physiol Pharmacol Off J Pol Physiol Soc. 2019;70(2). https://doi.org/10.26402/jpp.2019.2.09 Maroun P, Cooper MJW, Reid GD, Keirse MJNC. Relevance of gastrointestinal symptoms in endometriosis. Aust N Z J Obstet Gynaecol. 2009;49:411–414. https://doi.org/10.1111/j.1479-828X.2009.01030.x. Greene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril. 2009;91:32–39. https://doi.org/10.1016/j.fertnstert.2007.11.020. Schliep KC, Mumford SL, Peterson CM et al. Pain typology and incident endometriosis. Hum Reprod Oxf Engl. 2015;30:2427–2438. https://doi.org/10.1093/humrep/dev147. Jess T, Frisch M, Jørgensen KT, Pedersen BV, Nielsen NM. Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study. Gut. 2012;61:1279–1283. https://doi.org/10.1136/gutjnl-2011-301095. de Silva PS, Hansen HH, Wehberg S, Friedman S, Nørgård BM. Risk of Ectopic Pregnancy in Women With Inflammatory Bowel Disease: A 22-Year Nationwide Cohort Study. Clin Gastroenterol Hepatol. 2018;16:83-89.e1. https://doi.org/10.1016/j.cgh.2017.06.054. Stephansson O, Falconer H, Ludvigsson JF. Risk of endometriosis in 11,000 women with celiac disease. Hum Reprod Oxf Engl. 2011;26:2896–2901. https://doi.org/10.1093/humrep/der263. Aguiar FM, Melo SBC, Galvão LC, Rosa-e-Silva JC, dos Reis RM, Ferriani RA. Serological testing for celiac disease in women with endometriosis. A pilot study. Clin Exp Obstet Gynecol. 2009;36(1):23–25. Lacy BE, Mearin F, Chang L et al. Bowel Disorders. Gastroenterology. 2016;150:1393-1407.e5. https://doi.org/10.1053/j.gastro.2016.02.031. Schomacker ML, Hansen KE, Ramlau-Hansen CH, Forman A. Is endometriosis associated with irritable bowel syndrome? A cross-sectional study. Eur J Obstet Gynecol Reprod Biol. 2018;231:65–69. https://doi.org/10.1016/j.ejogrb.2018.10.023. Remorgida V, Ragni N, Ferrero S, Anserini P, Torelli P, Fulcheri E. The involvement of the interstitial Cajal cells and the enteric nervous system in bowel endometriosis. Hum Reprod Oxf Engl. 2005;20:264–271. https://doi.org/10.1093/humrep/deh568. Moore JS, Gibson PR, Perry RE, Burgell RE. Endometriosis in patients with irritable bowel syndrome: Specific symptomatic and demographic profile, and response to the low FODMAP diet. Aust N Z J Obstet Gynaecol. 2017;57:201–205. https://doi.org/10.1111/ajo.12594. Meurs-Szojda MM, Mijatovic V, Felt-Bersma RJF, Hompes PGA. Irritable bowel syndrome and chronic constipation in patients with endometriosis. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2011;13:67–71. https://doi.org/10.1111/j.1463-1318.2009.02055.x. Lee CE, Yong PJ, Williams C, Allaire C. Factors Associated with Severity of Irritable Bowel Syndrome Symptoms in Patients with Endometriosis. J Obstet Gynaecol Can JOGC J Obstet Gynecol Can JOGC. 2018;40:158–164. https://doi.org/10.1016/j.jogc.2017.06.025. Lea R a, Bancroft K b, Whorwell PJ a. Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology. J Gastroenterol. 2004;16(12):1269–1272. Issa B, Onon TS, Agrawal A et al. Visceral hypersensitivity in endometriosis: a new target for treatment? Gut. 2012;61:367–372. https://doi.org/10.1136/gutjnl-2011-300306. Droz J, Howard FM. Use of the Short-Form McGill Pain Questionnaire as a diagnostic tool in women with chronic pelvic pain. J Minim Invasive Gynecol. 2011;18:211–217. https://doi.org/10.1016/j.jmig.2010.12.009. Saidi K, Sharma S, Ohlsson B. A systematic review and meta-analysis of the associations between endometriosis and irritable bowel syndrome. Eur J Obstet Gynecol Reprod Biol. 2020;246:99–105. https://doi.org/10.1016/j.ejogrb.2020.01.031. Zondervan KT, Cardon LR, Kennedy SH. The genetic basis of endometriosis. Curr Opin Obstet Gynecol. 2001;13:309–314. Falcone T, Flyckt R. Clinical Management of Endometriosis. Obstet Gynecol. 2018;131:557–571. https://doi.org/10.1097/AOG.0000000000002469. Zhang T, De Carolis C, Man GCW, Wang CC. The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmun Rev. 2018;17:945–955. https://doi.org/10.1016/j.autrev.2018.03.017. Zhang RJ, Wild RA, Ojago JM. Effect of tumor necrosis factor-alpha on adhesion of human endometrial stromal cells to peritoneal mesothelial cells: an in vitro system. Fertil Steril. 1993;59:1196–1201. https://doi.org/10.1016/s0015-0282(16)55976-7. Iwabe T, Harada T, Tsudo T et al. Tumor necrosis factor-alpha promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression. J Clin Endocrinol Metab. 2000;85:824–829. https://doi.org/10.1210/jcem.85.2.6335. Viganò D, Zara F, Usai P. Irritable bowel syndrome and Endometriosis: new insights for old diseases. Dig Liver Dis. 2017;50. https://doi.org/10.1016/j.dld.2017.12.017 Anaf V, Chapron C, El Nakadi I, De Moor V, Simonart T, Noël JC. Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril. 2006;86:1336–1343. https://doi.org/10.1016/j.fertnstert.2006.03.057. Robles A, Perez Ingles D, Myneedu K et al. Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta-analysis. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2019;31:e13718. https://doi.org/10.1111/nmo.13718. Bashashati M, Moossavi S, Cremon C, et al. Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2018;30(1). https://doi.org/10.1111/nmo.13192 Barbara G, Wang B, Stanghellini V et al. Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome. Gastroenterology. 2007;132:26–37. https://doi.org/10.1053/j.gastro.2006.11.039. Pacchiarotti A, Milazzo GN, Biasiotta A et al. Pain in the upper anterior-lateral part of the thigh in women affected by endometriosis: study of sensitive neuropathy. Fertil Steril. 2013;100:122–126. https://doi.org/10.1016/j.fertnstert.2013.02.045. Abd El-Kader AI, Gonied AS, Lotfy Mohamed M, Lotfy Mohamed S. Impact of Endometriosis-Related Adhesions on Quality of Life among Infertile Women. Int J Fertil Steril. 2019;13:72–76. https://doi.org/10.22074/ijfs.2019.5572. Tabibian N, Swehli E, Boyd A, Umbreen A, Tabibian JH. Abdominal adhesions: A practical review of an often overlooked entity. Ann Med Surg. 2017;15:9–13. https://doi.org/10.1016/j.amsu.2017.01.021. Pichetshote N, Pimentel M. An Approach to the Patient With Chronic Undiagnosed Abdominal Pain. Off J Am Coll Gastroenterol ACG. 2019;114:726–732. https://doi.org/10.14309/ajg.0000000000000130. Tornblom H, Drossman D. Centrally targeted pharmacotherapy for chronic abdominal pain. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2015;27. https://doi.org/10.1111/nmo.12509 Grundström H, Gerdle B, Alehagen S, Berterö C, Arendt-Nielsen L, Kjølhede P. Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis. Acta Obstet Gynecol Scand. 2019;98:327–336. https://doi.org/10.1111/aogs.13508. Van Oudenhove L, Demyttenaere K, Tack J, Aziz Q. Central nervous system involvement in functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2004;18:663–680. https://doi.org/10.1016/j.bpg.2004.04.010. Hall GBC, Kamath MV, Collins S et al. Heightened central affective response to visceral sensations of pain and discomfort in IBS. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2010;22:276-e80. https://doi.org/10.1111/j.1365-2982.2009.01436.x. Klem F, Wadhwa A, Prokop LJ et al. Prevalence, Risk Factors, and Outcomes of Irritable Bowel Syndrome After Infectious Enteritis: A Systematic Review and Meta-analysis. Gastroenterology. 2017;152:1042-1054.e1. https://doi.org/10.1053/j.gastro.2016.12.039. Pimentel M, Lembo A. Microbiome and Its Role in Irritable Bowel Syndrome. Dig Dis Sci. 2020;65:829–839. https://doi.org/10.1007/s10620-020-06109-5. Leonardi M, Hicks C, El-Assaad F, El-Omar E, Condous G. Endometriosis and the microbiome: a systematic review. BJOG Int J Obstet Gynaecol. 2020;127:239–249. https://doi.org/10.1111/1471-0528.15916. Jenkins S, Olive DL, Haney AF. Endometriosis: pathogenetic implications of the anatomic distribution. Obstet Gynecol. 1986;67:335–338. Audebert A, Petousis S, Margioula-Siarkou C, Ravanos K, Prapas N, Prapas Y. Anatomic distribution of endometriosis: A reappraisal based on series of 1101 patients. Eur J Obstet Gynecol Reprod Biol. 2018;230:36–40. https://doi.org/10.1016/j.ejogrb.2018.09.001. Alborzi S, Hosseini-Nohadani A, Poordast T, Shomali Z. Surgical outcomes of laparoscopic endometriosis surgery: a 6 year experience. Curr Med Res Opin. 2017;33:2229–2234. https://doi.org/10.1080/03007995.2017.1362377. Zwas FR, Lyon DT. Endometriosis. An important condition in clinical gastroenterology. Dig Dis Sci. 1991;36(3):353–364. https://doi.org/10.1007/BF01318209 DiVasta AD, Vitonis AF, Laufer MR, Missmer SA. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood. Am J Obstet Gynecol. 2018;218:324.e1-324.e11. https://doi.org/10.1016/j.ajog.2017.12.007. Roman H, Ness J, Suciu N et al. Are digestive symptoms in women presenting with pelvic endometriosis specific to lesion localizations? A preliminary prospective study†. Hum Reprod. 2012;27:3440–3449. https://doi.org/10.1093/humrep/des322. Bharadwaj S, Barber MD, Graff LA, Shen B. Symptomatology of irritable bowel syndrome and inflammatory bowel disease during the menstrual cycle. Gastroenterol Rep. 2015;3:185–193. https://doi.org/10.1093/gastro/gov010. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39:535–549. https://doi.org/10.1016/j.ogc.2012.10.002. Hickey M, Ballard K, Farquhar C. Endometriosis. BMJ 2014;348:g1752. https://doi.org/10.1136/bmj.g1752. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod Oxf Engl. 2002;17:2715–2724. https://doi.org/10.1093/humrep/17.10.2715. Yang MH, Wang PH, Wang SJ, Sun WZ, Oyang YJ, Fuh JL. Women with Endometriosis Are More Likely to Suffer from Migraines: A Population-Based Study. PLOS ONE. 2012;7:e33941. https://doi.org/10.1371/journal.pone.0033941. Laganà AS, La Rosa VL, Rapisarda AMC et al. Anxiety and depression in patients with endometriosis: impact and management challenges. Int J Womens Health. 2017;9:323–330. https://doi.org/10.2147/IJWH.S119729. Lermann J, Mueller A, Körber F et al. Evaluation of high-sensitivity C-reactive protein in comparison with C-reactive protein as biochemical serum markers in women with endometriosis. Fertil Steril. 2010;93:2125–2129. https://doi.org/10.1016/j.fertnstert.2009.01.072. Liu E, Nisenblat V, Farquhar C, et al. Urinary biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2015;(12):CD012019. https://doi.org/10.1002/14651858.CD012019 Gupta D, Hull ML, Fraser I, et al. Endometrial biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;4:CD012165. https://doi.org/10.1002/14651858.CD012165 May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16:651–674. https://doi.org/10.1093/humupd/dmq009. 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;37:257–263. https://doi.org/10.1002/uog.8858. Hsu AL, Khachikyan I, Stratton P. Invasive and non-invasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol. 2010;53:413–419. https://doi.org/10.1097/GRF.0b013e3181db7ce8. Foti PV, Farina R, Palmucci S et al. Endometriosis: clinical features, MR imaging findings and pathologic correlation. Insights Imaging. 2018;9:149–172. https://doi.org/10.1007/s13244-017-0591-0. Saccardi C, Cosmi E, Borghero A, Tregnaghi A, Dessole S, Litta P. Comparison between transvaginal sonography, saline contrast sonovaginography and magnetic resonance imaging in the diagnosis of posterior deep infiltrating endometriosis. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2012;40:464–469. https://doi.org/10.1002/uog.11102. Walter AJ, Hentz JG, Magtibay PM, Cornella JL, Magrina JF. Endometriosis: correlation between histologic and visual findings at laparoscopy. Am J Obstet Gynecol. 2001;184(7):1407–1411; discussion 1411–1413. https://doi.org/10.1067/mob.2001.115747 Gubbels AL, Li R, Kreher D et al. Prevalence of occult microscopic endometriosis in clinically negative peritoneum during laparoscopy for chronic pelvic pain. Int J Gynecol Obstet. 2020;151:260–266. https://doi.org/10.1002/ijgo.13303. Grandi G, Toss A, Cortesi L, Botticelli L, Volpe A, Cagnacci A. The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life. BioMed Res Int. 2015;2015:751571. https://doi.org/10.1155/2015/751571. Agarwal SK, Chapron C, Giudice LC et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019;220:354.e1-354.e12. https://doi.org/10.1016/j.ajog.2018.12.039. Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: Endometriosis. Accessed August 4, 2022. https://academic.oup.com/hropen/article/2022/2/hoac009/6537540 Practice bulletin no. 114: management of endometriosis. Obstet Gynecol. 2010;116:223–236. https://doi.org/10.1097/AOG.0b013e3181e8b073. Nezhat C, Vang N, Tanaka PP, Nezhat C. Optimal Management of Endometriosis and Pain. Obstet Gynecol. 2019;134:834–839. https://doi.org/10.1097/AOG.0000000000003461. Yantiss RK, Clement PB, Young RH. Endometriosis of the intestinal tract: a study of 44 cases of a disease that may cause diverse challenges in clinical and pathologic evaluation. Am J Surg Pathol. 2001;25:445–454. https://doi.org/10.1097/00000478-200104000-00003. Wu CY, Chang WP, Chang YH, Li CP, Chuang CM. The risk of irritable bowel syndrome in patients with endometriosis during a 5-year follow-up: a nationwide population-based cohort study. Int J Colorectal Dis. 2015;30:907–912. https://doi.org/10.1007/s00384-015-2218-6. Seaman HE, Ballard KD, Wright JT, de Vries CS. Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case–control study—Part 2. BJOG. 2008;115:1392–1396. https://doi.org/10.1111/j.1471-0528.2008.01879.x. Smorgick N, Marsh CA, As-Sanie S, Smith YR, Quint EH. Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis. J Pediatr Adolesc Gynecol. 2013;26:171–175. https://doi.org/10.1016/j.jpag.2012.12.006. Surrey ES, Soliman AM, Johnson SJ, Davis M, Castelli-Haley J, Snabes MC. Risk of developing comorbidities among women with endometriosis: a retrospective matched cohort study. J Womens Health (Larchmt). 2018;27:1114–1123. https://doi.org/10.1089/jwh.2017.6432 Funding None to report. Author information Authors and Affiliations Contributions VY, NM, and SP inception of the work, drafting of the work, analysis, and revision. JN and JW introduced key content, generated key concepts, and performed critical review. All coauthors have approved the final version as submitted. Corresponding author Ethics declarations Conflict of interest None to report. 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. About this article Cite this article Yu, V., McHenry, N., Proctor, S. et al. Gastroenterologist Primer: Endometriosis for Gastroenterologists. Dig Dis Sci 68, 2482–2492 (2023). https://doi.org/10.1007/s10620-022-07674-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10620-022-07674-7