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Cited by 418Endometriosis Research and TreatmentGynecological conditions and treatmentsEctopic Pregnancy Diagnosis and Management

The pathophysiology of endometriosis and adenomyosis, tissue injury and repair

Open access
Leyendecker, G., Wildt, L., Mall, G.·2009·Archives of Gynecology and Obstetrics
DOI 10.1007/s00404-009-1191-0PMC PMC2730449
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Abstract

INTRODUCTION: This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women affected with the disease. METHODS: In women suffering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology as well as clinical aspects. The relevant molecular biologic aspects were compared to those of tissue injury and repair (TIAR) mechanisms reported in literature. RESULTS AND CONCLUSIONS: Circumstantial evidence suggests that endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatizations with the activation of the mechanism of 'tissue injury and repair' (TIAR). This results in the local production of estrogen. With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with the ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis. In late premenopausal adenomyosis, such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life leads to the same extent of microtraumatization. With the activation of the TIAR mechanism followed by infiltrative growth and chronic inflammation, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principle the same pathophysiology. In conclusion, endometriosis and adenomyosis result from the physiological mechanism of 'tissue injury and repair' (TIAR) involving local estrogen production in an estrogen-sensitive environment normally controlled by the ovary.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper proposes that endometriosis and adenomyosis share a pathophysiology driven by uterine peristalsis-induced tissue injury and repair (TIAR), with local estrogen production causing self-perpetuating hyperperistalsis and auto-traumatization. It integrates prior morphological, imaging, molecular, and clinical evidence into a unifying model rather than reporting a new primary study.

Key findings

  • Endometriosis and adenomyosis are proposed to result from trauma: chronic uterine peristaltic activity or hyperperistalsis induces microtraumatization at the endometrial–myometrial interface near the fundo-cornual raphe, activating TIAR and local estrogen production.
  • Locally produced estrogen acts in a paracrine fashion on the archimyometrium, interfering with ovarian control of uterine peristalsis, leading to permanent hyperperistalsis and self-perpetuation; overt auto-traumatization then dislocates basal endometrium into the peritoneal cavity and infiltrates the myometrium.
  • Iatrogenic uterine trauma (e.g., hysterotomy, curettage) may act as a strong one-time “first-step” injury; in rhesus monkeys, a history of estrogen patches plus hysterotomy trauma showed a significant association with endometriosis.
  • The basal endometrium in women with endometriosis is twice as thick as in healthy women; ER and PR expression declined in the functionalis and rose in the basalis and endometriotic lesions across the secretory phase, suggesting physiological progesterone resistance in basal/ectopic tissue rather than generalized progesterone resistance.

Methods

  • Narrative review/model synthesis: critical analysis of uterine morphology and function in women with endometriosis and adenomyosis and in normal controls using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology, and clinical aspects.
  • Relevant molecular biologic aspects were compared with tissue injury and repair (TIAR) mechanisms reported in the literature.
  • No new primary cohort or trial is described; evidence is drawn from prior studies and clinical/experimental observations.

Limitations

  • Not stated in the paper: no formal limitations section.
  • Evident from the text: conclusions are based on “circumstantial evidence” and a proposed unifying model; causal mechanisms are inferred rather than prospectively tested.
  • Evident from the text: this is a narrative synthesis without systematic search or quantitative meta-analysis, and some elements are explicitly speculative (e.g., “tempting to speculate” about cycle irregularities).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s00404-009-1191-0

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 96 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    As in healthy women, with progression of the secretory phase, ER and PR expression declined in the functionalis and steadily rose in the basalis as well as in the endometriotic lesions.

    “As in healthy women, with the progression of the secretory phase, the ER and PR expression declined in the functionalis and steadily rose in the basalis as well as in the endometriotic lesions [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source

      Not checked in the free run.

  • Findingnone given

    Using immunohistochemistry of estradiol receptor alpha and progesterone receptor, no progesterone resistance could be observed in the late secretory phase of the functional endometrium of affected women.

    “Using immunohistochemistry of estradiol receptor alpha and progesterone receptor no progesterone resistance could be observed in the late secretory phase of the functional endometrium of affected women.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Adenomyotic foci are usually localized in the anterior and/or posterior with preference of the posterior but only rarely in the lateral walls of the uterine corpus.

    “Adenomyotic foci are usually localized in the anterior and/or posterior with preference of the posterior but only rarely in the lateral walls of the uterine corpus.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source

      Not checked in the free run.

    • cites [23] Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G (2005) Adenomyosis in endometriosis—prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod 20:2309–2316 source

      Not checked in the free run.

    • cites [45] Leyendecker G (2000) Endometriosis is an entity with extreme pleiomorphism. Hum Reprod 15:4–7 source

      Not checked in the free run.

  • Premisecitation

    Fragments of basal endometrium are found in the menstrual effluent with a higher prevalence in women with endometriosis than in controls.

    “Fragments of basal endometrium were found in the menstrual effluent with a higher prevalence in women with endometriosis than in controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source

      Not checked in the free run.

  • Premisecitation

    Molecular mechanisms associated with mechanical strain, injury, and repair display a similar pattern in different tissues and involve expression of P450 aromatase and local production of estrogen.

    “Moreover, it became apparent that the molecular mechanisms associated with mechanical strain, injury, and repair displays a pattern that is quite similar in different tissues and involves the expression of the P450 aromatase and the local production of estrogen [20].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712 source

      Not checked in the free run.

  • May combine two claims. 16
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Premisecitation

    Uterine function of rapid and directed sperm transport into the dominant tube is dysfunctional in women with endometriosis and is characterized by hyper- and dysperistalsis.

    “The uterine function of rapid and directed sperm transport into the ‘dominant tube’ is dysfunctional in women with endometriosis and is characterized by hyper- and dysperistalsis [27–32].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [27] Mäkäräinen L (1988) Uterine contractions in endometriosis: effects of operative and danazol treatment. Obstet Gynecol 9:134–138 source

      Not checked in the free run.

    • cites [28] Salamanca A, Beltran E (1995) Subendometrial contractility in menstrual phase visualised by transvaginal sonography in patients with endometriosis. Fertl Steril 64:193–195 source

      Not checked in the free run.

    • cites [29] Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H (1996) Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility. Hum Reprod 11:1542–1551 source

      Not checked in the free run.

    • cites [30] Bulletti C, De Ziegler D, Polli V, Del Ferro E, Palini S, Flamigni C (2002) Characteristics of uterine contractility during menses in women with mild to moderate endometriosis. Fertil Steril 77:1156–1161 source

      Not checked in the free run.

    • cites [31] Kissler S, Hamscho N, Zangos S, Wiegratz I, Schlichter S, Menzel C, Doebert N, Gruenwald F, Vogl TJ, Gaetje R, Rody A, Siebzehnruebl E, Kunz G, Leyendecker G, Kaufmann M (2006) Uterotubal transport disorder in adenomyosis and endometriosis—a cause for infertility. BJOG 113:902–908 source

      Not checked in the free run.

    • cites [32] Kissler S, Zangos S, Wiegratz I, Kohl J, Rody A, Gaetje R, Doebert N, Wildt L, Kunz G, Leyendecker G, Kaufmann M (2007) Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis. Ann N Y Acad Sci 1101:38–48 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and self-perpetuation of the disease process.

    “With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with the ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Hyperperistalsis and increased intrauterine pressure result in myometrial dehiscences that are infiltrated by basal endometrium with secondary development of peristromal muscular tissue.

    “Hyperperistalsis and increased intrauterine pressure would with time, result in myometrial dehiscences that are infiltrated by basal endometrium with the secondary development of peristromal muscular tissue.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Cyr61 is up-regulated in eutopic endometrium in women with endometriosis and also in ectopic lesions as well as in experimental endometriosis.

    “A highly estrogen-dependent gene, Cyr61, is up-regulated in eutopic endometrium in women with endometriosis and also in ectopic lesions as well as in experimental endometriosis [42, 43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Absenger Y, Hess-Stumpp H, Kreft B, Kratzschmar J, Haendler B, Schutze N, Regidor PA, Winterhager E (2004) Cyr61, a deregulated gene in endometriosis. Mol Hum Reprod 10:399–407 source

      Not checked in the free run.

    • cites [43] Gashaw I, Hastings JM, Jackson KS, Winterhager E, Fazleabas AT (2006) Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria. Biol Reprod 74:1060–1066 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Pelvic endometriosis results from transtubal dislocation of fragments of basal endometrium.

    “it was suggested that pelvic endometriosis results from the transtubal dislocation of fragments of basal endometrium [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    In late premenopausal adenomyosis, such a causal event might not have occurred.

    “In late premenopausal adenomyosis, such an event might not have occurred.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Uterine dysfunction in women with endometriosis and adenomyosis is a result of archimetral hyperestrogenism.

    “It was suggested that this uterine dysfunction in women with endometriosis and adenomyosis is a result of archimetral hyperestrogenism [3, 4, 29, 33].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source

      Not checked in the free run.

    • cites [4] Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4:752–762 source

      Not checked in the free run.

    • cites [29] Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H (1996) Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility. Hum Reprod 11:1542–1551 source

      Not checked in the free run.

    • cites [33] Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G, Kissler S, Noe M, Wildt L (2004) Uterine peristaltic activity and the development of endometriosis. Ann NY Acad Sci 1034:338–355 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The non-pregnant uterus is constantly active throughout the reproductive period of life and is subjected to mechanical strain.

    “It became evident that the non-pregnant uterus is constantly active throughout the reproductive period of life and thereby, like other mechanically active organs of the body such as the skeletal and the cardiovascular systems, respectively, rather inevitably subjected to mechanical strain.”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [12] De Vries K, Lyons EA, Ballard G, Levi CS, Lindsay DJ (1990) Contractions of the inner third of the myometrium. Am J Obstet Gynaecol 162:679–682 source

      Not checked in the free run.

    • cites [13] Lyons EA, Taylor PJ, Zheng XH, Ballard G, Levi CS, Kredentser JV (1991) Characterisation of subendometrial myometrial contractions throughout the menstrual cycle in normal fertile women. Fertil Steril 55:771–775 source

      Not checked in the free run.

    • cites [14] Williams M, Hill CJ, Scudamore I, Dunphy B, Cooke ID, Barratt CLR (1993) Sperm numbers and distribution within the human fallopian tube around ovulation. Hum Reprod 8:2019–2026 source

      Not checked in the free run.

    • cites [15] Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G (1996) The dynamics of rapid sperm transport through the female genital tract. Evidence from vaginal sonography of uterine peristalsis (VSUP) and hysterosalpingoscintigraphy (HSSG). Hum Reprod 11:627–632 source

      Not checked in the free run.

    • cites [16] Wildt L, Kissler S, Licht P, Becker W (1998) Sperm transport in the human female genital tract and its modulation by oxitocin as assessed by hystrosalpingography, hysterotonography, electrohysterography and Doppler sonography. Hum Reprod Update 4:655–666 source

      Not checked in the free run.

    • cites [17] Schmiedehausen K, Kat S, Albert N, Platsch G, Wildt L, Kuwert T (2003) Determination of velocity of tubar transport with dynamic hysterosalpingoscintigraphy. Aug Nucl Med Commun 24:865–870

      Not checked in the free run.

    • cites [18] Zervomanolakis I, Ott HW, Hadziomerovic D, Mattle V, Seeber BE, Virgolini I, Heute D, Kissler S, Leyendecker G, Wildt L (2007) Physiology of upward transport in the human female genital tract. Ann N Y Acad Sci 1101:1–20 source

      Not checked in the free run.

    • cites [19] Zervomanolakis I, Ott HW, Müller J, Seeber BE, Friess SC, Mattle V, Virgolini I, Heute D, Wildt L (2009) Uterine mechanisms of ipsilateral directed spermatozoa transport: evidence for a contribution of the utero-ovarian countercurrent system. Eur J Obstet Gynecol Reprod Biol 144(Suppl 1):S45–S49 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues.

    “Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis.

    “In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Clinical and experimental evidence do not support the views that susceptibility to endometriosis is acquired by epigenetic mechanisms during prenatal life or that the endometrium in women with endometriosis is inherently altered.

    “Clinical and experimental evidence do not support these views.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Hyperperistalsis causes overt uterine auto-traumatization, detachment of fragments of basal endometrium, and their transtubal dislocation into the peritoneal cavity as well as infiltrative growth of basal endometrium into the underlying myometrium, resulting in pelvic endometriosis and uterine adenomyosis.

    “As outlined previously, hyperperistalsis causes overt uterine auto-traumatization, detachment of fragments of basal endometrium, and their transtubal dislocation into the peritoneal cavity as well as infiltrative growth of basal endometrium into the underlying myometrium resulting in pelvic endometriosis and uterine adenomyosis, respectively [3, 33].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source

      Not checked in the free run.

    • cites [33] Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G, Kissler S, Noe M, Wildt L (2004) Uterine peristaltic activity and the development of endometriosis. Ann NY Acad Sci 1034:338–355 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    This is further magnified in an estrogen-sensitive environment normally controlled by the ovary.

    “This is further magnified in an estrogen-sensitive environment normally controlled by the ovary.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The uterus is physiologically highly estrogen sensitive.

  • May combine two claims.

    Premisecitation

    Following termination of unphysiological strain and healing, this process is down-regulated and local production of estrogen or up-regulation of estrogen-dependent genes ceases.

    “Following termination of unphysiological strain and healing, this process is down-regulated and the local production of estrogen or up-regulation of estrogen-dependent genes ceases [54, 57].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [54] Yang G, Im HJ, Wang JH (2005) Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene 363:166–172 source

      Not checked in the free run.

    • cites [57] Hadjiargyrou M, Ahrens W, Rubin CT (2000) Temporal expression of the chondrogenic and angiogenic growth factor CYR61 during fracture repair. J Bone Miner Res 15:1014–1023 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Both endometriosis and adenomyosis may be integrated into the physiological mechanism and new nosological concept of TIAR and may represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ.

    “Both, endometriosis and adenomyosis may now be integrated into the physiological mechanism and new nosological concept of “tissue injury and repair” (TIAR) and may, in this context, represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive, reproductive organ.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: All phenotypes of endometriosis share in principle the same pathophysiology and no parallel and separate mechanisms of their development exist.
    • Rests on an assumption: The uterus is physiologically highly estrogen sensitive.

  • May combine two claims.

    Interpretationreasoning

    With continuing hyperperistaltic activity and sustained injury, healing at the fundo-cornual raphe will not ensue and an increasing number of foci are involved in chronic injury, proliferation, and inflammation.

    “With continuing hyperperistaltic activity and sustained injury, however, healing at the fundo-cornual raphe will not ensue and an increasing number of foci are involved in this process of chronic injury, proliferation, and inflammation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The latter findings suggest physiological progesterone resistance in the basal endometrium and also in the endometriotic lesions as they are derived from implanted fragments of basal endometrium.

    “The latter findings suggest physiological progesterone resistance in the basal endometrium and also in the endometriotic lesions as they are derived from implanted fragments of basal endometrium.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Even minor increments in mechanical strain result in activation of COX-2 and production of PGE2, the basic biochemical mechanisms underlying tissue injury, and also in production of interleukin-8.

    “However, even minor increments in mechanical strain resulted and the activation of COX-2 and the production of PGE2, the basic biochemical mechanisms underlying tissue injury [54], and also in the production of interleukin-8 [65].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [54] Yang G, Im HJ, Wang JH (2005) Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene 363:166–172 source

      Not checked in the free run.

    • cites [65] Harada M, Osuga Y, Hirota Y, Koga K, Morimoto C, Hirata T, Yoshino O, Tsutsumi O, Yano T, Taketani Y (2005) Mechanical stretch stimulates interleukin-8 production in endometrial stromal cells: possible implications in endometrium-related events. J Clin Endocrinol Metab 90(2):1144–1148 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Interleukin-1-induced activation of COX-2 results in production of PGE2, which in turn activates STAR and P450 aromatase.

    “Interleukin-1-induced activation of the cyclooxygenase-2 enzyme (COX-2) results in the production of prostaglandin E2 (PGE2), which in turn activates STAR (steroidogenic acute regulatory protein) and the P450 aromatase.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [20] Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712 source

      Not checked in the free run.

    • cites [52] Sierra A, Lavaque E, Perez-Martin M, Azcoitia I, Hales DB, Garcia-Segura LM (2003) Steroidogenic acute regulatory protein in the rat brain: cellular distribution, developmental regulation and overexpression after injury. Eur J Neurosci 18:1458–1467 source

      Not checked in the free run.

    • cites [53] Lavaque E, Sierra A, Azcoitia I, Garcia-Segura LM (2006) Steroidogenic acute regulatory protein in the brain. Neuroscience 138:741–747 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Chronic trauma to ectopic lesions maintains the inflammatory process and results in the same tissue response as seen in uterine adenomyosis.

    “It appears that chronic trauma to the ectopic lesions maintains the inflammatory process and results in the same tissue response as seen in uterine adenomyosis [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While in healthy women the endometrial-myometrial lining is smooth and regular, it is irregular and sometimes polypoid in affected women.

    “Moreover, while in healthy women the endometrial–myometrial lining is smooth and regular it is irregular and sometimes polypoid in affected women [3, 81].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source

      Not checked in the free run.

    • cites [81] McBean JH, Gibson M, Brumsted JR (1996) The association of intrauterine filling defects on hysterosalpingogram with endometriosis. Fertil Steril 66:522–526 source

      Not checked in the free run.

21 of 21

  • The authors state this as an assumption.

    All phenotypes of endometriosis share in principle the same pathophysiology and no parallel and separate mechanisms of their development exist.

    “This endeavor is undertaken with the premise that all phenotypes of endometriosis share in principal the same pathophysiology and that no parallel and separate mechanisms of their development do exist.”

  • The paper relies on this without support.

    The uterus is physiologically highly estrogen sensitive.

    “when the tissue, as it is the case with the uterus, is physiologically highly estrogen sensitive and when injury is chronic in character.”

  • The paper relies on this without support.

    Abdominal wall endometriosis following cesarean section develops in presumably primarily healthy subjects.

    “Moreover, abdominal wall endometriosis following cesarean section develops in presumably primarily healthy subjects.”

  • The paper relies on this without support.

    During menstruation the basal endometrium is maximally exposed.

    “During menstruation the basal endometrium is maximally exposed.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Even within the TIAR framework, the pathogenesis of adenomyosis differs from that of endometriosis.

    “Regardless, even within the TIAR framework it seems evident that the pathogenesis of adenomyosis differs from that of endometriosis [28,29,30].”

    From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [30]

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Noble LS, Simpson ER, Johns A, Bulun SE (1996) Aromatas expression in endometriosis. J Clin Endocrinol Metab 81:174–179
  2. Kunz G, Kissler S, Wildt L, Leyendecker G (2000) Uterine peristalsis: directed sperm transport and fundal implantation of the blastocyst. In: Filicori M (ed) Endocrine basis of reproductive function. Monduzzi Editore, Bologna, Italy
  3. Peters H (1977) The human ovary in childhood and early maturity. Eur J Obstet Gynec Reprod Biol 9:137–144
  4. Meyer R (1919) Über den Stand der Frage der Adenomyositis und Adenome im allgemeinen und insbesondere über Adenomyositis seroepithelialis und Adenomyometritis sarcomatosa. Zbl Gynäkol 43:745–750

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Authors
Leyendecker, G., Wildt, L., & Mall, G.
Affiliations
  • Innsbruck Medical University (AT)
  • Klinikum Darmstadt (DE)
Corresponding author
Leyendecker, G.
ORCID
Wildt, L.
Venue
Archives of Gynecology and Obstetrics
Publisher
Springer Science and Business Media LLC
Published
2009-07-31
Volume
280
Issue
4
Pages
529-538
ISSN
  • 0003-9128 (ISSN-L)
  • 0932-0067
  • 1432-0711
DOI
10.1007/s00404-009-1191-0
PMC
PMC2730449
OpenAlex
W2148139435
Semantic Scholar
57846a48eac1d41e879291de7b663af3ae367596
Cited by
418
References
88
Citations by year
2026: 30 · 2025: 17 · 2024: 22 · 2023: 28 · 2022: 31 · 2021: 40 · 2020: 30 · 2019: 19 · 2018: 25 · 2017: 30 · 2016: 22 · 2015: 23 · 2014: 26 · 2013: 20 · 2012: 12
FWCI
20.80
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Archives of Gynecology and Obstetrics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
Keywords
endometriosis, adenomyosis, pathophysiology, tissue injury and repair, uterine peristalsis, local estrogen production, ectopic endometrial lesions, endometrium, chronic inflammation, paracrine signaling, uterine injury
MeSH terms
Adult, Endometriosis, Estrogens, Female, Humans, Iatrogenic Disease, Stress, Mechanical, Uterus, Wound Healing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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