Pathogenese der Endometriose: Bedeutung für Schmerzentstehung und Subfertilität

Zusammenfassung Endometriose ist ein häufiges Krankheitsbild mit großer Auswirkung auf das gesamte Leben einer Frau. Derzeitig besteht keine Aussicht auf Heilung, es gibt lediglich symptomatische Therapieansätze; umso wichtiger ist es, die Pathogenese und die Auswirkung dieser Erkrankung auf den Organismus besser zu verstehen. Kernproblem der Endometrioseentstehung scheinen gestörte Kontraktionsabläufe in der Gebärmutter zu sein, die zu einer Mikrotraumatisierung der Junktionalzone (Archimetrose) mit Aktivierung von Stammzellen führen, die transloziert werden und dann die Grundlage für ektope Läsionen bilden (Epithel‑, Stroma- und Muskelzellen), entweder in der Gebärmuttermuskelwand (Adenomyose) oder im kleinen Becken (Endometriose) bilden. Andere Faktoren, wie genetische und epigenetische Veränderungen, Immunreaktion und Mesothelveränderungen, können das Geschehen weiter beeinflussen. Die typischen Beschwerden dieser Erkrankung wie schwere Dysmenorrhö, zyklische und azyklische Unterbauchschmerzen (UBS), zyklische Dysurie und Dyschezie, Dyspareunie, sowie Infertilität sind hinlänglich bekannt und trotzdem wird die Erkrankung im Mittel erst 10 Jahre nach Einsetzen der Beschwerden diagnostiziert. Die Schmerzentstehung ist komplex. Sowohl periphere also auch zentrale Sensitivierung von Schmerzmechanismen, aber auch hormonelle, psychische und muskuläre Veränderungen spielen im Schmerzgeschehen eine große Rolle. Bei ausgeprägter Endometriose scheinen vor allem auch die anatomischen Veränderungen zu mechanischen Funktionsstörungen der Genitalorgane zu führen, dennoch gibt es viele Hinweise, dass auch die Inflammation, die ovarielle Funktionseinheit (Eizellreifung und -qualität, sowie die Eizellreserve) und der adenomyotische Uterus multifaktoriell die Fertilität der betroffenen Patientinnen beeinflussen können. Abstract Endometriosis is a common medical condition that has a significant impact on the lives of women suffering from it. Symptomatic therapeutic approaches are currently the only option available since there are no causal treatments for this disease. This makes it all the more important to better understand the pathogenesis and impact of endometriosis on the body in order to develop future treatments. The core problem of endometriosis development appears to be disturbed contraction processes in the uterus, which lead to the microtraumatisation of the junctional zone (archimetrosis) with activation of stem cells that translocate and then form the basis for ectopic lesions (epithelial, stroma and muscle cells) either in the uterine muscle wall (adenomyosis) or in the pelvis (endometriosis). Other factors such as genetic and epigenetic changes, immune response and mesothelial changes can further influence what happens. Typical symptoms of this disease are severe dysmenorrhoea, cyclical and non-cyclical pelvic pain, cyclical diarrhoea and dysuria, dyspareunia as well as infertility. Due to its complex symptoms, endometriosis is usually not diagnosed until on average 10 years after the onset of symptoms. The origin of pain is complex. Both peripheral and central sensitization of pain mechanisms, as well as hormonal, psychological and muscular changes, play a major role in the pain process. In the case of severe endometriosis, it is in particular the anatomical changes that appear to lead to the mechanical functional disorders of the genital organs. Nevertheless, there is much evidence that not only inflammation and the ovarian functional unit (egg cell maturation and quality, as well as the egg cell reserve), but also the adenomyotic uterus can have a multifactorial influence on the fertility of affected patients. Similar content being viewed by others Literatur Abrao MS, Podgaec S, Dias JA Jr et al (2006) Deeply infiltrating endometriosis affecting the rectum and lymph nodes. Fertil Steril 86:543–547 Akande VA, Hunt LP, Cahill DJ et al (2004) Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis. Hum Reprod 19:96–103 Anaf V, Simon P, El Nakadi I et al (2000) Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod 15:1744–1750 Aredo JV, Heyrana KJ, Karp BI et al (2017) Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction. Semin Reprod Med 35:88–97 As-Sanie S, Harris RE, Napadow V et al (2012) Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain 153:1006–1014 Attar E, Tokunaga H, Imir G et al (2009) Prostaglandin E2 via steroidogenic factor‑1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab 94:623–631 Ballweg ML (2004) Impact of endometriosis on women’s health: comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol 18:201–218 Barcena De Arellano ML, Gericke J, Reichelt U et al (2011) Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions. Hum Reprod 26:2721–2730 Barcena De Arellano ML, Mechsner S (2014) The peritoneum—an important factor for pathogenesis and pain generation in endometriosis. J Mol Med (Berl) 92:595–602 Borrelli G, Carvalho K, Kallas E et al (2013) Chemokines in the pathogenesis of endometriosis and infertility. J Reprod Immunol 98:1–9 Campo S, Campo V, Benagiano G (2012) Adenomyosis and infertility. Reprod Biomed Online 24:35–46 Chapron C, Pietin-Vialle C, Borghese B et al (2009) Associated ovarian endometrioma is a marker for greater severity of deeply infiltrating endometriosis. Fertil Steril 92:453–457 Cousins FL, Gargett CE (2018) Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol 50:27–38 De Graaff A, D’hooghe T, Dunselman G et al (2013) The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod 28:2677–2685 De Ziegler D, Borghese B, Chapron C (2010) Endometriosis and infertility: pathophysiology and management. Lancet 376:730–738 Dueholm M, Lundorf E, Hansen ES et al (2001) Magnetic resonance imaging and transvaginal ultrasonography for the diagnosis of adenomyosis. Fertil Steril 76:588–594 Exacoustos C, Luciano D, Corbett B et al (2013) The uterine junctional zone: a 3-dimensional ultrasound study of patients with endometriosis. Am J Obstet Gynecol 209:248.e1–248.e7 Ferrero S, Esposito F, Abbamonte LH et al (2005) Quality of sex life in women with endometriosis and deep dyspareunia. Fertil Steril 83:573–579 Garavaglia E, Sala C, Taccagni G et al (2017) Fertility preservation in endometriosis patients: anti-Müllerian hormone is a reliable marker of the ovarian follicle density. Front Surg 4:40 Garrido N, Navarro J, Garcia-Velasco J et al (2002) The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update 8:95–103 Greene R, Stratton P, Cleary SD et al (2009) Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril 91:32–39 Guo S‑W (2020) The pathogenesis of adenomyosis vis-à-vis endometriosis. J Clin Med 9:485 Halis G, Arici A (2004) Endometriosis and inflammation in infertility. Ann NY Acad Sci 1034:300–315 Hoffman D (2015) Central and peripheral pain generators in women with chronic pelvic pain: patient centered assessment and treatment. Curr Rheumatol Rev 11:146–166 Horikawa T, Nakagawa K, Ohgi S et al (2008) The frequency of ovulation from the affected ovary decreases following laparoscopic cystectomy in infertile women with unilateral endometrioma during a natural cycle. J Assist Reprod Genet 25:239–244 Ibrahim MG, Sillem M, Plendl J et al (2017) Myofibroblasts are evidence of chronic tissue microtrauma at the endometrial–myometrial junctional zone in uteri with adenomyosis. Reprod Sci 24:1410–1418 Ibrahim MG, Sillem M, Plendl J et al (2019) Arrangement of myofibroblastic and smooth muscle-like cells in superficial peritoneal endometriosis and a possible role of transforming growth factor beta 1 (TGFβ1) in myofibroblastic metaplasia. Arch Gynecol Obstet 299:489–499 Karande VC, Pratt DE, Rao R et al (1995) Elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis. Fertil Steril 64:1070–1073 Keckstein J, Ulrich U, Kandolf O et al (2003) Die laparoskopische Therapie der Darmendometriose und der Stellenwert der medikamentösen Therapie. Zentralbl Gynakol 125:259–266 Kissler S, Hamscho N, Zangos S et al (2006) Uterotubal transport disorder in adenomyosis and endometriosis—A cause for infertility. BJOG 113:902–908 Kunz G, Beil D, Huppert P et al (2005) Adenomyosis in endometriosis—prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 20:2309–2316 Lafay Pillet M, Huchon C, Santulli P et al (2014) A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod 29:1666–1676 Leyendecker G, Herbertz M, Kunz G et al (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 Leyendecker G, Wildt L (2019) Evolutionäre Aspekte in der Pathogenese und Pathophysiologie von Adenomyose und Endometriose. J Gynäkol Endokrinol AT 29:110–121 Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280:529–538 Lin Y‑H, Chen Y‑H, Chang H‑Y et al (2018) Chronic niche inflammation in endometriosis-associated infertility: current understanding and future therapeutic strategies. Int J Mol Sci 19:2385 Marcoux S, Maheux R, Berube S et al (1997) Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 337:217–222 Martínez-Conejero JA, Morgan M, Montesinos M et al (2011) Adenomyosis does not affect implantation, but is associated with miscarriage in patients undergoing oocyte donation. Fertil Steril 96:943–950.e1 Mechsner S (2016) Endometriose. Schmerz 30:477–490 Mechsner S, Bartley J, Infanger M et al (2009) Clinical management and immunohistochemical analysis of umbilical endometriosis. Arch Gynecol Obstet 280:235–242 Mechsner S, Weichbrodt M, Riedlinger W et al (2008) Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study. Hum Reprod 23:2202–2209 Medicine PCOTaSFR (2012) Endometriosis and infertility: a committee opinion. Fertil Steril 98:591–598 Meyer R (1930) Adenofibrosis und adenomyosis. In: von Stoeckel W (Hrsg) Veit’s Handbuch der Gynäkologie. Springer, Berlin, S 511–515 Ng N, Wahl K, Orr NL et al (2020) Endometriosis and negative perception of the medical profession. J Obstet Gynaecol Can 42:248–255 Ota H, Igarashi S, Hatazawa J et al (1998) Is adenomyosis an immune disease? Hum Reprod Update 4:360–367 Pellicer A, Oliveira N, Ruiz A et al (1995) Exploring the mechanism (s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. Hum Reprod 10:91–97 Sampson JA (1927) Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 3:93 Sampson JA (1927) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469 Scheerer C, Bauer P, Chiantera V et al (2016) Characterization of endometriosis-associated immune cell infiltrates (EMaICI). Arch Gynecol Obstet 294:657–664 Shebl O, Ebner T, Sommergruber M et al (2009) Anti-Mullerian hormone serum levels in women with endometriosis: a case-control study. Gynecol Endocrinol 25:713–716 Somigliana E, Ragni G, Benedetti F et al (2003) Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles. Hum Reprod 18:2450–2453 Strathy JH, Molgaard CA, Coulam CB et al (1982) Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril 38:667–672 Symons LK, Miller JE, Kay VR et al (2018) The immunopathophysiology of endometriosis. Trends Mol Med 24:748–762 Vercellini P, Somigliana E, Vigano P et al (2009) Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod 24:254–269 Xu B, Guo N, Zhang X‑M et al (2015) Oocyte quality is decreased in women with minimal or mild endometriosis. Sci Rep 5:10779 Youm HS, Choi YS, Han HD (2011) In vitro fertilization and embryo transfer outcomes in relation to myometrial thickness. J Assist Reprod Genet 28:1135–1140 Young VJ, Brown JK, Saunders PT et al (2013) The role of the peritoneum in the pathogenesis of endometriosis. Hum Reprod Update 19:558–569 Stratton P, Berkley KJ (2011) Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update 17(3):327–346. https://doi.org/10.1093/humupd/dmq050 Author information Authors and Affiliations Corresponding author Ethics declarations Interessenkonflikt S. Mechsner gibt an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Additional information Redaktion L. Kiesel, Münster W. Janni, Ulm Rights and permissions About this article Cite this article Mechsner, S. Pathogenese der Endometriose: Bedeutung für Schmerzentstehung und Subfertilität. Gynäkologe 53, 645–657 (2020). https://doi.org/10.1007/s00129-020-04665-5 Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00129-020-04665-5