Editing Endometriosis (section)

====Retrograde menstruation theory====
The theory of retrograde menstruation (also called the ''implantation theory'' or ''transplantation theory'') is the most commonly accepted theory for the dissemination and transformation of ectopic endometrium into endometriosis. It suggests that during a woman's [[menstruation|menstrual flow]], some of the endometrial debris flow backward through the fallopian tubes and into the peritoneal cavity, attaching itself to the [[peritoneum|peritoneal surface]] (the lining of the abdominal cavity) where it can proceed to invade the tissue as or transform into endometriosis. It is unclear at what stage the transformation of endometrium, or any cell of origin such as stem cells or coelomic cells (see those theories below), to endometriosis begins.<ref name="Fauser2011">{{cite journal | vauthors = Fauser BC, Diedrich K, Bouchard P, Domínguez F, Matzuk M, Franks S, Hamamah S, Simón C, Devroey P, Ezcurra D, Howles CM | title = Contemporary genetic technologies and female reproduction | journal = Human Reproduction Update | volume = 17 | issue = 6 | pages = 829–47 | year = 2011 | pmid = 21896560 | pmc = 3191938 | doi = 10.1093/humupd/dmr033 }}</ref><ref name="vanderLinden1996"/><ref name="koninckx1999">{{cite journal | vauthors = Koninckx PR, Barlow D, Kennedy S | title = Implantation versus infiltration: the Sampson versus the endometriotic disease theory | journal = Gynecologic and Obstetric Investigation | volume = 47 | issue = Supplement 1 | pages = 3–9; discussion 9–10 | date = 1999 | pmid = 10087422 | doi = 10.1159/000052853 | s2cid = 29718095 }}</ref>

Proofs in support of the theory are based on retrospective epidemiological studies that an association with endometrial implants attached to the peritoneal cavity, which would develop into endometrial lesions and retrograde menstruation; and the fact that animals like rodents and non-human primates whose endometrium is not shed during the estrous cycle don't develop naturally endometriosis contrary to animals that have a natural menstrual cycle like rhesus monkeys and baboons.<ref name="Malvezzi Marengo Podgaec Piccinato p. ">{{cite journal | vauthors = Malvezzi H, Marengo EB, Podgaec S, Piccinato CA | title = Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology | journal = Journal of Translational Medicine | volume = 18 | issue = 1 | page = 311 | date = August 2020 | pmid = 32787880 | pmc = 7425005 | doi = 10.1186/s12967-020-02471-0 | publisher = Springer Science and Business Media LLC | doi-access = free | title-link = doi }}</ref>

Retrograde menstruation alone is not able to explain all instances of endometriosis, and additional factors such as genetics, immunology, stem cell migration, and coelomic metaplasia (see "Other theories" on this page) are needed to account for disseminated disease and why many individuals with retrograde menstruation are not diagnosed with endometriosis. In addition, endometriosis has shown up in people who have never experienced menstruation including cisgender men,<ref name="pmid445352">{{cite journal | vauthors = Pinkert TC, Catlow CE, Straus R | title = Endometriosis of the urinary bladder in a man with prostatic carcinoma | journal = Cancer | volume = 43 | issue = 4 | pages = 1562–7 | date = April 1979 | pmid = 445352 | doi = 10.1002/1097-0142(197904)43:4<1562::aid-cncr2820430451>3.0.co;2-w | doi-access = free | title-link = doi }}</ref> fetuses,<ref name="signorile2009"/> and prepubescent girls.<ref>{{cite journal | vauthors = Mok-Lin EY, Wolfberg A, Hollinquist H, Laufer MR | title = Endometriosis in a patient with Mayer-Rokitansky-Küster-Hauser syndrome and complete uterine agenesis: evidence to support the theory of coelomic metaplasia | journal = Journal of Pediatric and Adolescent Gynecology | volume = 23 | issue = 1 | pages = e35-7 | date = February 2010 | pmid = 19589710 | doi = 10.1016/j.jpag.2009.02.010 }}</ref><ref name="Marsh EE 2004">{{cite journal | vauthors = Marsh EE, Laufer MR | title = Endometriosis in premenarcheal girls who do not have an associated obstructive anomaly | journal = Fertility and Sterility | volume = 83 | issue = 3 | pages = 758–60 | date = March 2005 | pmid = 15749511 | doi = 10.1016/j.fertnstert.2004.08.025 | doi-access = free | title-link = doi }}</ref> Further theoretical additions are needed to complement the retrograde menstruation theory to explain why cases of endometriosis show up in the [[brain]]<ref>{{cite journal | vauthors = Thibodeau LL, Prioleau GR, Manuelidis EE, Merino MJ, Heafner MD | title = Cerebral endometriosis. Case report | journal = Journal of Neurosurgery | volume = 66 | issue = 4 | pages = 609–10 | date = April 1987 | pmid = 3559727 | doi = 10.3171/jns.1987.66.4.0609 | doi-access = free | title-link = doi }}</ref> and lungs.<ref>{{cite journal | vauthors = Rodman MH, Jones CW | title = Catamenial hemoptysis due to bronchial endometriosis | journal = The New England Journal of Medicine | volume = 266 | issue = 16 | pages = 805–8 | date = April 1962 | pmid = 14493132 | doi = 10.1056/nejm196204192661604 }}</ref>

Researchers are investigating the possibility that the immune system may be unable to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to [[autoimmune disease]], [[allergy|allergic]] reactions, and the impact of toxic materials.<ref name="Lino">{{cite journal|author-link1=Norbert Gleicher | vauthors = Gleicher N, el-Roeiy A, Confino E, Friberg J | title = Is endometriosis an autoimmune disease? | journal = Obstetrics and Gynecology | volume = 70 | issue = 1 | pages = 115–22 | date = July 1987 | pmid = 3110710 }}</ref><ref>{{cite journal | vauthors = Capellino S, Montagna P, Villaggio B, Sulli A, Soldano S, Ferrero S, Remorgida V, Cutolo M | title = Role of estrogens in inflammatory response: expression of estrogen receptors in peritoneal fluid macrophages from endometriosis | journal = Annals of the New York Academy of Sciences | volume = 1069 | pages = 263–7 | date = June 2006 | issue = 1 | pmid = 16855153 | doi = 10.1196/annals.1351.024 | bibcode = 2006NYASA1069..263C | s2cid = 35601442 }}</ref> It is still unclear what, if any, causal relationship exists between toxic materials or autoimmune disease and endometriosis. There are immune system changes in people with endometriosis, such as an increase in macrophage-derived secretion products, but it is unknown if these contribute to the disorder or are reactions to it.<ref name="Young2013">{{cite journal | vauthors = Young VJ, Brown JK, Saunders PT, Horne AW | title = The role of the peritoneum in the pathogenesis of endometriosis | journal = Human Reproduction Update | volume = 19 | issue = 5 | pages = 558–69 | year = 2013 | pmid = 23720497 | doi = 10.1093/humupd/dmt024 | doi-access = free | title-link = doi }}</ref>

Endometriotic lesions differ in their biochemistry, hormonal response, immunology, and inflammatory response compared to the endometrium.<ref name=zondervan32212520/><ref name="pmid12372441">{{cite journal |vauthors=Redwine DB |title=Was Sampson wrong? |journal=Fertility and Sterility |volume=78 |issue=4 |pages=686–93 |date=October 2002 |pmid=12372441 |doi=10.1016/S0015-0282(02)03329-0 |doi-access=free |title-link=doi}}</ref> This is likely because the cells that give rise to endometriosis are a side population of cells.<ref name=Fauser2011/> Similarly, there are changes in, for example, the [[mesothelium]] of the peritoneum in people with endometriosis, such as loss of [[tight junction]]s. It is unknown if these are causes or effects of the disorder.<ref name=Young2013/>

In rare cases where [[imperforate hymen]] does not resolve itself before the first menstrual cycle and goes undetected, blood and endometrium are trapped within the uterus until the problem is resolved by surgical incision. Many health care practitioners never encounter this defect, and due to the [[flu-like symptoms]], it is often misdiagnosed or overlooked until multiple menstrual cycles have passed. By the time a correct diagnosis has been made, endometrium and other fluids have filled the uterus and Fallopian tubes with results similar to retrograde menstruation, resulting in endometriosis. The initial stage of endometriosis may vary based on the time elapsed between onset and surgical procedure.{{citation needed|date=March 2016}}

The theory of retrograde menstruation as a cause of endometriosis was first proposed by [[John A. Sampson]].<ref name="vanderLinden1996"/><ref name=sampson27ajppmcid>{{cite journal |vauthors=Sampson JA |title=Metastatic or Embolic Endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation |journal=Am. J. Pathol. |volume=3 |issue=2 |pages=93–110.43 |date=March 1927 |pmid=19969738 |pmc=1931779 }}</ref>