The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index; none of the 96 sources its claims cite is checked for support yet.
The pathophysiology of endometriosis and adenomyosis, tissue injury and repair
Open accessAbstract
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.
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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).
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In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > The eutopic endometrium in endometriosis and the endometriotic lesions
What the sources say
- Not checked yetcites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > The eutopic endometrium in endometriosis and the endometriotic lesions
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [45] Leyendecker G (2000) Endometriosis is an entity with extreme pleiomorphism. Hum Reprod 15:4–7 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Fragments of basal endometrium were found in the menstrual effluent with a higher prevalence in women with endometriosis than in controls.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [20] Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The local production of estrogen both on the level of the eutopic endometrium in women with endometriosis and of the ectopic lesions is, undoubtedly, central to the understanding of the pathophysiology of the disease.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The enigma of archimetral hyperestrogenism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In comparison to normal controls and in contrast to peripheral blood estradiol levels are elevated in menstrual blood of women with endometriosis and adenomyosis [34].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [34] Takahashi K, Nagata H, Kitao M (1989) Clinical usefulness of determination of estradiol levels in the menstrual blood for patients with endometriosis. Acta Obstet Gynecol Jpn 41:1849–1850
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Recent studies have increasingly shown that estradiol is of utmost importance in the process of wound healing [49–51].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Tissue injury and repair (TIAR)
What the sources say
- Not checked yetcites [49] Ashcroft GS, Ashworth JJ (2003) Potential role of estrogens in wound healing. Am J Clin Dermatol 4:737–743 source
- Not checked yetcites [50] Gilliver SC, Ashworth JJ, Ashcroft GS (2007) The hormonal regulation of cutaneous wound healing. Clin Dermatol 25:56–62 source
- Not checked yetcites [51] Mowa CN, Hoch R, Montavon CL, Jesmin S, Hindman G, Hou G (2008) Estrogen enhances wound healing in the penis of rats. Biomed Res 29:267–270 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“There is a significant association of pelvic endometriosis with uterine adenomyosis in women and in the baboon with life-long infertility.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [22] Kunz G, Beil D, Huppert P, Leyendecker G (2000) Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod 15:76–82 source
- Not checked yetcites [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 yetcites [24] Kunz G, Herbertz M, Beil D, Huppert P, Leyendecker G (2007) Adenomyosis as a disorder of the early and late human reproductive period. Reprod Biomed Online 15:681–685 source
- Not checked yetcites [25] Dueholm M, Lundorf E, Hansen ES, Sørensen JS, Ledertoug S, Olesen F (2001) Magnetic resonance imaging and transvaginal ultrasonography for the diagnosis of adenomyosis. Fertil Steril 76:588–594 source
- Not checked yetcites [26] Barrier BF, Malinowski MJ, Dick EJ Jr, Hubbard GB, Bates GW (2004) Adenomyosis in the baboon is associated with primary infertility. Fertil Steril 82(Suppl 3):1091–1094 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“On the basis of the data presented above we had suggested that auto-traumatization of the uterus would constitute the critical factor in the development of endometriosis and adenomyosis [3, 4, 33].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 5
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [27] Mäkäräinen L (1988) Uterine contractions in endometriosis: effects of operative and danazol treatment. Obstet Gynecol 9:134–138 source
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Abstract > Results and conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [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 yetcites [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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“it was suggested that pelvic endometriosis results from the transtubal dislocation of fragments of basal endometrium [21].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [21] Leyendecker G, Herbertz M, Kunz G, Mall G (2002) Endometriosis results from the dislocation of basal endometrium. Hum Reprod 17:2725–2736 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✗ Asserted: fails✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In late premenopausal adenomyosis, such an event might not have occurred.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Abstract > Results and conclusions
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It was suggested that this uterine dysfunction in women with endometriosis and adenomyosis is a result of archimetral hyperestrogenism [3, 4, 29, 33].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The role of the uterus in the disease process
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Abstract > Results and conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Abstract > Results and conclusions
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinical and experimental evidence do not support these views.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > The enigma of archimetral hyperestrogenism
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > Second step injury: auto-traumatization by hyperperistalsis
What the sources say
- Not checked yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is further magnified in an estrogen-sensitive environment normally controlled by the ovary.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: The uterus is physiologically highly estrogen sensitive.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Tissue injury and repair (TIAR)
What the sources say
- Not checked yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Conclusions
Tests✓ Asserted: passes? Checkable: unclear✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > First step injury: microtraumatization
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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 pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > The eutopic endometrium in endometriosis and the endometriotic lesions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > First step injury: microtraumatization
What the sources say
- Not checked yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Tissue injury and repair (TIAR)
What the sources say
- Not checked yetcites [20] Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712 source
- Not checked yetcites [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 yetcites [53] Lavaque E, Sierra A, Azcoitia I, Garcia-Segura LM (2006) Steroidogenic acute regulatory protein in the brain. Neuroscience 138:741–747 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“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].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > The eutopic endometrium in endometriosis and the endometriotic lesions
What the sources say
- Not checked yetcites [3] Leyendecker G, Kunz G, Kissler S, Wildt L (2006) Adenomyosis and reproduction. Best Pract Res Clin Obstet Gynaecol 20:523–546 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, while in healthy women the endometrial–myometrial lining is smooth and regular it is irregular and sometimes polypoid in affected women [3, 81].”
§ The pathophysiology of endometriosis and adenomyosis: tissue injury and repair > Mechanism of disease: uterine auto-traumatization > The eutopic endometrium in endometriosis and the endometriotic lesions
What the sources say
- Not checked yetcites [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 yetcites [81] McBean JH, Gibson M, Brumsted JR (1996) The association of intrauterine filling defects on hysterosalpingogram with endometriosis. Fertil Steril 66:522–526 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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.”
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?
In the citing paper
“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]
Citations
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BackgroundIatrogenic peritoneal adenomyoma after laparoscopic subtotal hysterectomy and uterine morcellation
Donnez, O., Jadoul, P., Squifflet, J. P., & Donnez, J. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.06.009 · Cited by 43 · cited 1×
“This does, however, not exclude various and diVerent etiologies at the very onset of the disease process including iatrogenic [ 5 ], exogenous [6, 7], and hereditary [8] factors.”
BackgroundThe association of intrauterine filling defects on hysterosalpingogram with endometriosis
McBean, J. H., Gibson, M., & Brumsted, J. R. (1996) · Fertility and Sterility · doi:10.1016/s0015-0282(16)58562-8 · Cited by 40
Ultrastructural epithelial zonation of the primate endometrium (rhesus monkey)
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Self-citationShioyama, R., Aoki, Y., Ito, H., et al. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00788.2007 · Cited by 26 · cited 1×
“53] and urinary bladder tissue as well as studies with isolated connective tissue such as Wbroblasts and cartilage [54–56] have revealed that tissue injury and inXammation with subsequent healing is associated with a speciWc physiological process that involves the local production of estrogen from its precursors.”
BackgroundFriedler, S., Raziel, A., Schachter, M., Strassburger, D., Komarovsky, D., Bern, O., Soffer, Y., Kasterstein, E., & Ron‐El, R. (1999) · Human Reproduction · doi:10.1093/humrep/14.suppl_3.101 · Cited by 26
Uterine contractions in endometriosis: Effects of operative and danazol treatment
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Estrogen enhances wound healing in the penis of rats
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“Recent studies have increasingly shown that estradiol is of utmost importance in the process of wound healing [49– 51].”
BackgroundGene expression of oxytocin receptor in human ectopic endometrial tissues.
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Self-citation
Flagged first, then by citations
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Cited by
Sorted by citations
What we know about primary dysmenorrhea today: a critical review.
Iacovides, S., Avidon, I., & Baker, F. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv039 · Cited by 973
“…have recently proposed that the high intrauterine pressure, peristalsis, and myometrial contractions that account for primary dysmenorrheic pain, result in mechanical strain and injury of the uterus, and ultimately, may drive the development of adenomyosis (Leyendecker et al., 2009, 2015).”
BackgroundEndometriosis and infertility: pathophysiology and management
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Endometrial stem/progenitor cells: the first 10 years
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“Theories suggest that chronic microtrauma to the JZ from chronic peristaltic myometrial contractions causes repeated cycles of tissue injury and repair (Leyendecker et al., 2009).”
BackgroundThe Pathogenesis of Endometriosis: Molecular and Cell Biology Insights
Laganà, A. S., Garzon, S., Götte, M., Viganò, P., Franchi, M. P., Ghezzi, F., & Martin, D. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225615 · Cited by 503
“At the same time, when women with symptomatic endometriosis are compared with women without or minimal disease, the differences were reported not only at the level of endometriosis implants but even at the level of eutopic endometrium [66], uterus [67], and peritoneal environment [68].”
BackgroundPathogenesis of endometriosis: The genetic/epigenetic theory
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“Interestingly, microtraumas are also observed in the endometrial-myometrial JZ (239), which is consistent with the Archimetra theory (265, 266).”
Metadata
- 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
- Published
- 2009-07-31
- Volume
- 280
- Issue
- 4
- Pages
- 529-538
- ISSN
- 0003-9128 (ISSN-L)
- 0932-0067
- 1432-0711
- 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
- hybrid
- doi.org
- 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 › Obstetrics and Gynecology › 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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
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