Endometriosis causes
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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]
Causes
The exact cause of endometriosis remains incompletely understood. Current evidence suggests that endometriosis results from a combination of retrograde menstruation, genetic predisposition, hormonal influences, and immune dysregulation.
Retrograde Menstruation and Lesion Formation
Retrograde efflux of endometrial cells through the fallopian tubes into the pelvic cavity during menstruation is widely accepted as a contributor to the origin of endometriosis lesions within the abdominal–pelvic cavity.[1][2][3]
Lymphatic or vascular dissemination has also been proposed and cannot be excluded as a mechanism contributing to extrapelvic lesions.[1][2][3]
However, retrograde menstruation alone does not fully explain why only a subset of individuals develop clinically significant disease.
Genetic Predisposition
Twin studies estimate the heritability of endometriosis to be approximately 50%.[4][5]
A family history of endometriosis is a significant risk factor. Among sisters of affected individuals, the relative risk is 5.2 (95% CI, 3.4–7.2).[6]
Although heritability appears substantial, no single gene has been identified as responsible for the majority of familial cases.[4][5][6]
Early Menarche
Earlier onset of menstruation is associated with increased risk.
Menarche before age 12 years is associated with increased risk of endometriosis.[7]
This may increase cumulative lifetime exposure to retrograde menstrual efflux.
Short Menstrual Cycle Length
Shorter menstrual cycles (<28 days) are associated with increased risk.[8]
More frequent menses may increase the frequency of retrograde efflux and implantation events.
Low Body Mass Index
Lower body mass index has been associated with increased risk of endometriosis.[9]
The mechanism underlying this association remains unclear but may involve hormonal or inflammatory factors.
Nulliparity
Nulliparity is associated with increased risk of endometriosis.[10]
The protective mechanism of pregnancy may involve prolonged anovulation and suppression of menstruation.
Obstructive Müllerian Anomalies
Obstructive Müllerian anomalies are strongly associated with endometriosis.
In individuals with uterine anomalies causing blockage of menstrual outflow, the prevalence of endometriosis is reported as 47% (95% CI, 36%–58%).[11]
Obstruction likely increases retrograde menstrual efflux and promotes implantation of endometrial tissue within the pelvis.
References
- ↑ 1.0 1.1 Saunders PTK, Horne AW. Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807-2824. doi:10.1016/j.cell.2021.04.041
- ↑ 2.0 2.1 Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-1256. doi:10.1056/NEJMra1810764
- ↑ 3.0 3.1 Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379:e070750. doi:10.1136/bmj-2022-070750
- ↑ 4.0 4.1 Saha R, Pettersson HJ, Svedberg P, et al. Heritability of endometriosis. Fertil Steril. 2015;104 (4):947-952. doi:10.1016/j.fertnstert.2015.06.035
- ↑ 5.0 5.1 Treloar SA, O’Connor DT, O’Connor VM, Martin NG. Genetic influences on endometriosis in an Australian twin sample. Fertil Steril. 1999;71(4):701-710. doi:10.1016/S0015-0282(98)00540-8
- ↑ 6.0 6.1 Stefansson H, Geirsson RT, Steinthorsdottir V, et al. Genetic factors contribute to the risk of developing endometriosis. Hum Reprod. 2002;17 (3):555-559. doi:10.1093/humrep/17.3.555
- ↑ LuMY, Niu JL, Liu B. The risk of endometriosis by early menarche is recently increased: ameta-analysis of literature published from 2000 to 2020. Arch Gynecol Obstet. 2023;307(1):59-69. doi:10.1007/s00404-022-06541-0
- ↑ Wei M, Cheng Y, Bu H, Zhao Y, ZhaoW. Length of menstrual cycle and risk of endometriosis: ameta-analysis of 11 case-control studies. Medicine (Baltimore). 2016;95(9):e2922. doi:10.1097/MD.0000000000002922
- ↑ Liu Y, ZhangW. Association between body mass index and endometriosis risk: ameta-analysis. Oncotarget. 2017;8(29):46928-46936. doi:10.18632/oncotarget.14916
- ↑ Missmer SA, Hankinson SE, Spiegelman D, et al. Reproductive history and endometriosis among premenopausal women. Obstet Gynecol. 2004;104 (5 Pt 1):965-974. doi:10.1097/01.AOG.0000142714.54857.f8
- ↑ Vercellini P, Salmeri N, Somigliana E, et al. Müllerian anomalies and endometriosis as potential explanatory models for the retrograde menstruation/implantation and the embryonic remnants/celomic metaplasia pathogenic theories: a systematic review and meta-analysis. Hum Reprod. 2024;39(7):1460-1470. doi:10.1093/humrep/deae086