Endometriosis natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Overview

Endometriosis affects females in the reproductive age group. Endometriosis has a wide spectrum of presentations. It can be asymptomatic, present with premenstrual spotting and cyclical abdominal pain, present with infertility or chronic pelvic pain, or present as deep endometriosis with dyspareunia, dyschezia, and cyclical rectal bleeding. Complications of endometriosis include infertility, fibrosis, chocolate cyst, and rarely, other organs such as the lungs can be affected.

Endometriosis is a chronic, estrogen-dependent inflammatory disease.[1]

The mean time from symptom onset to diagnosis is approximately 7 years.[2]

Pain severity does not reliably correlate with lesion number, location, or subtype (except deep posterior cul-de-sac disease, which correlates with dyspareunia).[3][4]

Natural History, Complications and Prognosis

Natural History

Endometriosis is a condition affecting females in the reproductive age group. Endometriosis has a wide spectrum of presentations; it may be asymptomatic or present with premenstrual spotting and cyclical abdominal pain. Endometriosis may also present with infertility or chronic pelvic pain, or as deep endometriosis presenting with dyspareunia, dyschezia, and cyclical rectal bleeding. The progression of the disease, if left untreated, is variable. It can progress to a severe disease or regress or remain the same. Severe disease is called deep endometriosis. It presents with chronic pelvic pain, infertility, and other complications due to the extensive fibrosis of the pelvic structures.[5][6]

Lesion progression is associated with localized fibrosis, angiogenesis, and coordinated nerve and blood vessel ingrowth, which contribute to structural distortion and chronic pain.[7][8]

Endometriosis demonstrates a heterogeneous clinical course. Some individuals experience stable symptoms, while others develop progressive deep infiltrating disease involving the bowel, bladder, or ureter.[7]

In less than 1% of patients, deep endometriosis may result in bowel obstruction, hydroureter, hematochezia, or hematuria.[9][10]

Pain associated with endometriosis may involve nociceptive, neuropathic, and nociplastic mechanisms.[11][12]

Central sensitization may develop, leading to amplification of pain signals, widespread body pain, fatigue, sleep disturbance, and cognitive symptoms.[11][12]

Pain may persist despite hormonal suppression or surgical excision of lesions.[11][12]

Complications

The major complication of endometriosis is infertility; Endometriosis is identified in approximately 20% to 50% of individuals with infertility.[13]

Infertility may result from impaired ovarian function, adhesions causing tubal obstruction, and dysfunction of the uterine endometrium.[8]

Common Complications

Common complications of endometriosis include:[14][15]

  • Internal abdominal organ scarring
  • Adhesions
  • Pelvic cysts
  • Chocolate cysts
  • Ruptured cyst
  • Endometriosis is also associated with chronic overlapping pain conditions, including irritable bowel syndrome, bladder pain syndrome, and pelvic floor myalgia.[11][12]

Less Common Complications

Less common complications of endometriosis include:

  • Bowel obstruction  
  • Ureteral obstruction or hydroureter  
  • Hematochezia  
  • Hematuria  
  • Thoracic endometriosis presenting with catamenial pneumothorax or hemoptysis[16]

Malignant Transformation

Endometriosis is associated with an increased risk of ovarian cancer.[17][18][19]

Prognosis

Prognosis of endometriosis varies with medical therapy. The majority of patients improve with medical therapy, but symptoms may recur in 30-40% of patients after the completion of treatment.[20]

Pain improvement following surgical excision is variable, and symptom recurrence may occur even in the absence of visible recurrent lesions.[11][12]

Endometriosis is a chronic condition, and long-term management may be required.

References

  1. Tomassetti C, Johnson NP, Petrozza J, et al; InternationalWorking Group of AAGL, ESGE, ESHRE and WES. An international terminology for endometriosis, 2021. Hum Reprod Open. 2021;2021(4):hoab029. doi:10.1093/hropen/hoab029
  2. Allaire C, BedaiwyMA, Yong PJ. Diagnosis and management of endometriosis. CMAJ. 2023;195 (10):E363-E371. doi:10.1503/cmaj.220637
  3. Pashkunova D, Darici E, Senft B, et al. Lesion size and location in deep infiltrating bowel endometriosis: correlation with gastrointestinal dysfunction and pain. Acta Obstet Gynecol Scand.2024;103(9):1764-1770. doi:10.1111/aogs.14921
  4. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266-271. doi:10.1093/humrep/del339
  5. Wenger JM, Loubeyre P, Marci R, Dubuisson JB (2009). "[Endometriosis: review of the literature and clinical management]". Rev Med Suisse. 5 (222): 2085–6, 2088–90. PMID 19947450.
  6. Brawn J, Morotti M, Zondervan KT, Becker CM, Vincent K (2014). "Central changes associated with chronic pelvic pain and endometriosis". Hum Reprod Update. 20 (5): 737–47. doi:10.1093/humupd/dmu025. PMC 4501205. PMID 24920437.
  7. 7.0 7.1 Saunders PTK, Horne AW. Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807-2824. doi:10.1016/j.cell.2021.04.041
  8. 8.0 8.1 Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ.2022;379:e070750. doi:10.1136/bmj-2022-070750
  9. Mușat F, Păduraru DN, Bolocan A, Constantinescu A, Ion D, Andronic O. Endometriosis as an uncommon cause of intestinal obstruction—a comprehensive literature review. J Clin Med.2023;12(19):6376. doi:10.3390/jcm12196376
  10. Leone Roberti Maggiore U, Ferrero S, Candiani M, Somigliana E, Viganò P, Vercellini P. Bladder endometriosis: a systematic review of pathogenesis, diagnosis, treatment, impact on fertility, and risk of malignant transformation. EurUrol. 2017;71(5):790-807. doi:10.1016/j.eururo.2016.12.015
  11. 11.0 11.1 11.2 11.3 11.4 Coxon L, Demetriou L, Vincent K. Current developments in endometriosis-associated pain. Cell Rep Med. 2024;5(10):101769. doi:10.1016/j.xcrm.2024.101769
  12. 12.0 12.1 12.2 12.3 12.4 Kaplan CM, Kelleher E, Irani A, Schrepf A, Clauw DJ, Harte SE. Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms. Nat Rev Neurol. 2024;20(6):347-363. doi:10.1038/s41582-024-00966-8
  13. Hamdan M, Omar SZ, Dunselman G, Cheong Y. Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis. Obstet Gynecol. 2015;125(1):79-88. doi:10.1097/AOG.0000000000000592
  14. Donnez J, Donnez O, Orellana R, Binda MM, Dolmans MM (2016). "Endometriosis and infertility". Panminerva Med. 58 (2): 143–50. PMID 26837776.
  15. Karaman Y, Uslu H (2015). "Complications and their management in endometriosis surgery". Womens Health (Lond). 11 (5): 685–92. doi:10.2217/whe.15.55. PMID 26315050.
  16. AndresMP, Arcoverde FVL, Souza CCC, Fernandes LFC, Abrão MS, Kho RM. Extrapelvic endometriosis: a systematic review. J Minim Invasive Gynecol. 2020;27(2):373-389. doi:10.1016/j.jmig.2019.10.004
  17. Gibbons T, Rahmioglu N, Zondervan KT, Becker CM. Crimson clues: advancing endometriosis detection and management with novel blood biomarkers. Fertil Steril. 2024;121(2):145-163. doi:10.1016/j.fertnstert.2023.12.018
  18. Leyland N, Casper R, Laberge P, Singh SS; SOGC. Endometriosis: diagnosis and management. J Obstet Gynaecol Can. 2010;32(7)(suppl 2):S1-S32. doi:10.1016/S1701-2163(16)34589-3
  19. Brown J, Crawford TJ, Allen C, Hopewell S, Prentice A. Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev. 2017;1(1):CD004753. doi:10.1002/14651858.CD004753.pub4
  20. Leone Roberti Maggiore U, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V; et al. (2016). "A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes". Hum Reprod Update. 22 (1): 70–103. doi:10.1093/humupd/dmv045. PMID 26450609.