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
Cites
Sampson, J. A. (1927) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30003-x · Cited by 2,334 · cited 1×
“In this respect, the signiWcance of menstruation in the disease process [72] should be more precisely deWned.”
BackgroundBulun, S. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804690 · Cited by 1,772
(1927) · PubMed Central · Cited by 1,008
Burney, R. O., Talbi, S., Hamilton, A. E., Vo, K. C., Nyegaard, M., Nezhat, C. R., Lessey, B. A., & Giudice, L. C. (2007) · Endocrinology · doi:10.1210/en.2006-1692 · Cited by 735 · cited 2×
“With respect to the expression of the 17HSD type 2 no data are available that distinguish between functionalis and basalis [ 83 , 85].”
BackgroundAromatase expression in endometriosis.
Noble, L. S., Simpson, E. R., Johns, A., & Bulun, S. E. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.1.8550748 · Cited by 566
Kunz, G., Beil, D., Deininger, H., Wildt, L., & Leyendecker, G. (1996) · Human Reproduction · doi:10.1093/humrep/11.3.627 · Cited by 408
Self-citationProgesterone resistance in endometriosis: link to failure to metabolize estradiol.
Bulun, S. E., Cheng, Y.-H., Yin, P., Imir, G., Utsunomiya, H., Attar, E., Innes, J., & Julie Kim, J. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.11.041 · Cited by 397 · cited 1×
“This might explain at least in part the Wnding of ‘progesterone resistance’ [40, 82 , 83], and an impaired estradiol metabolism in the endometrium of women with endometriosis [41, 80].”
BackgroundGarcía‐Segura, L. M., Wozniak, A., Azcoitia, Í., Rodríguez, J., Hutchison, R. E., & Hutchison, J. B. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00340-6 · Cited by 379 · cited 1×
“This cascade can even be activated in tissue that normally does not express the P450 aromatase indicating the basic physiological signiWcance of the local production of estrogen in tissue injury and repair (TIAR) [ 58 ].”
BackgroundKunz, G., Beil, D., Huppert, P., Noe, M., Kissler, S., & Leyendecker, G. (2005) · Human Reproduction · doi:10.1093/humrep/dei021 · Cited by 377 · cited 1×
“usually present close to the “fundo-cornual raphe” of the archimyometrium [3, 23, 45] (Figs.”
BackgroundSelf-citationSimón, C., Gutiérrez, A., Vidal, A., de los Santos, M. J., Tarín, J. J., Remohí, J., & Pellicer, A. (1994) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a138578 · Cited by 374 · cited 1×
“Moreover, clinical studies with oocyte donation do not support a generally impeded implantation in women with endometriosis [84].”
Background
Flagged first, then by citations
Research works printed but not linked: 4
- Noble LS, Simpson ER, Johns A, Bulun SE (1996) Aromatas expression in endometriosis. J Clin Endocrinol Metab 81:174–179
- 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
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Cited by
Sorted by citations
Items 101–200 of 415
Yıldız, Ş., Kinali, M., Wei, J., Milad, M. P., Yin, P., Adli, M., & Bulun, S. E. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.01.041 · Cited by 46
“Another explanation, proposed by Leyendecker, describes a “tissue injury and repair” mechanism that is activated by hyperestrogenism and hyperperistalsis leading to uterine autotraumatization (6, 7).”
Lymphangiogenesis in deep infiltrating endometriosis
Keichel, S., Barcena de Arellano, M. L., Reichelt, U., Riedlinger, W. F. J., Schneider, A., Kohler, C., & Mechsner, S. (2011) · Human Reproduction · doi:10.1093/humrep/der230 · Cited by 44
“the theory of retrograde transplantation of endometriotic tissue (Sampson, 1927) and currently, the tissue injury and repair (TIAR) concept (Leyendecker et al., 2009).”
Adenomyosis and Infertility: A Literature Review
Pados, G., Gordts, S., Sorrentino, F., Nisolle, M., Nappi, L., & Daniilidis, A. (2023) · Medicina · doi:10.3390/medicina59091551 · Cited by 56
“The TIAR hypothesis has recently been expanded to lump endometriosis and adenomyosis together as one disease, called archimetriosis [15–18].”
BackgroundAdenomyosis: What the Patient Needs
Alabiso, G., ALIO, L., Arena, S., di Prun, A. B., Bergamini, V., Berlanda, N., Busacca, M., Candiani, M., Centini, G., Cello, A. D., et al. (2016) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2015.12.017 · Cited by 43
Does Nutrition Affect Endometriosis?
Helbig, M., Vesper, A.-S., Beyer, I., & Fehm, T. (2021) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-1207-0557 · Cited by 43
“The subsequent repair mechanisms then increase the intrauterine movement, thus creating a vicious circle by which more loose endometrial cells are transported away [14].”
BackgroundStreuli, I., Santulli, P., Chouzenoux, S., Chapron, C., & Batteux, F. (2015) · Reproductive Sciences · doi:10.1177/1933719115589410 · Cited by 43
“Iatrogenic lesions to the uterus caused by interventions such as cesarean section or curettage as well as pregnancy and labor themselves can cause microtraumatizations with a disruption in the endometrium–myometrium interface that activates tissue injury and repair mechanisms that can lead to the development of adenom…”
BackgroundUterine disorders and iron deficiency anemia
Donnez, J., Carmona, F., Maitrot‐Mantelet, L., Dolmans, M., & Chapron, C. (2022) · Fertility and Sterility · doi:10.1016/j.fertnstert.2022.08.011 · Cited by 49
Uterine peristalsis-induced stresses within the uterine wall may sprout adenomyosis
Shaked, S., Jaffa, A. J., Grisaru, D., & Elad, D. (2014) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-014-0614-4 · Cited by 41
“As a result, the structural arrangement of the muscle fibers in the myometrium is disrupted leading to reduction in the contractile ability of the myometrial layer and dysperistalsis of the uterus (Leyeyndecker and Wildt 2011; Leyendecker et al. 2009).”
BackgroundRemodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis
Barcena, M. L., Oldeweme, J., Arnold, J., Schneider, A., & Mechsner, S. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.05.013 · Cited by 40
Endometriosis and Adenomyosis: From Pathogenesis to Follow-Up
Martire, F. G., Costantini, E., d’Abate, C., Schettini, G., Sorrenti, G., Centini, G., Zupi, E., & Lazzeri, L. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47050298 · Cited by 46
“Ectopic basal endometrial debris in the peritoneal cavity can induce chronic local inflammation and activate TIAR mechanisms, promoting a cascade reaction characterized by local estrogen production, proliferation, and infiltrative growth, resulting in endometriotic lesion formation [60,61].”
Liu, J., Liu, X., Duan, K., Zhang, Y., & Guo, S. (2012) · Reproductive Sciences · doi:10.1177/1933719112443876 · Cited by 39
“It has been reported that in women with chronic pain, with or without endometriosis, the uteri endometrium, myometrium, isthmus, cervix, and vagina may all be reinnervated,(6,70-73) which has been theorized to be the consequence of tissue injury resulting from difficult vaginal deliveries and/or straining during defac…”
BackgroundStephens, V. R., Rumph, J. T., Ameli, S., Bruner‐Tran, K. L., & Osteen, K. G. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2021.807685 · Cited by 42
Reproductive outcome in 326 women with unicornuate uterus
Tellum, T., Bracco, B., Braud, L. V. D., Knez, J., Ashton‐Barnett, R., Amin, T., Chaggar, P., & Jurkovic, D. (2022) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.26073 · Cited by 39
Adenomyosis and Adolescence: A Challenging Diagnosis and Complex Management
Martire, F. G., d’Abate, C., Schettini, G., Cimino, G., Ginetti, A., Colombi, I., Cannoni, A., Centini, G., Zupi, E., & Lazzeri, L. (2024) · Diagnostics · doi:10.3390/diagnostics14212344 · Cited by 38
“Since data suggest that ovulation suppression is important for endometriosis regression, some theorize that adenomyosis may respond similarly [13].”
BackgroundHao, M., Liu, X., & Guo, S. (2020) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2020.07.023 · Cited by 40
“The tissue injury and repair theory also attempts to account for the pathogenesis of endometriosis (Leyendecker and Wildt, 2011; Leyendecker et al., 2009; Leyendecker et al., 2015).”
BackgroundMethodInfluentialXia, W., Zhang, D., Ouyang, J., Liang, Y., Zhang, H., Huang, Z., Liang, G., Zhu, Q., Guan, X., & Zhang, J. (2018) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-018-0361-y · Cited by 37
“the same physiological mechanism of “tissue injury and repair” (TIAR) [7] and can be regarded as variants of the”
BackgroundArchimetrosis: the evolution of a disease and its extant presentation
LEYENDECKER, G., Wildt, L., Laschke, M. W., & Mall, G. (2022) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-022-06597-y · Cited by 38
“The activation of the non-organ-specific, but physiological TIAR process for local production of estradiol and formation of the also non-organ-specific basal morphogenetic complex for attraction of mesenchymal stem cells (MSCs) to the site of trauma.”
BackgroundInfluentialSelf-citationStratopoulou, C. A., Cussac, S., d'Argent, M., Donnez, J., & Dolmans, M. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.01.001 · Cited by 37
Endometriosis: the consequence of uterine denervation–reinnervation
Quinn, M. J. (2011) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-011-2063-y · Cited by 35
“nomyosis [37, 38].”
Dueholm, M., & Hjorth, I. M. D. (2016) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2016.09.010 · Cited by 34
Role of Hormones in Common Benign Uterine Lesions: Endometrial Polyps, Leiomyomas, and Adenomyosis
Kossaï, M., & Penault-Llorca, F. M. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-38474-6_3 · Cited by 41
Organoids of the Female Reproductive Tract: Innovative Tools to Study Desired to Unwelcome Processes
Heremans, R., Jan, Ž., Timmerman, D., & Vankelecom, H. E. J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.661472 · Cited by 36
Myostatin, follistatin and activin type II receptors are highly expressed in adenomyosis
Carrarelli, P., Yen, C., Arcuri, F., Funghi, L., Tosti, C., Wang, T., Huang, J. S., & Petraglia, F. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.05.032 · Cited by 34
Guo, J.-B., Gao, J.-M., Yu, X., Luo, H., Xiong, X.-S., & Huang, O. (2015) · Gynecologic and Obstetric Investigation · doi:10.1159/000365569 · Cited by 35
Li, Y., Zhang, S., Shi-en, Z., Xia, X., & Bao, L. (2011) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-9-30 · Cited by 35
“Adenomyosis is associated with recurrent and aggressive pain syndrome, impaired immune status, and also characterized by intensified weighted uterus and a high rate of spontaneous abortion [2-4,29].”
BackgroundBenign and malignant pathology of the uterus
Tanos, V., & Berry, K. E. (2017) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2017.10.004 · Cited by 34
“defined JZ, myometrial cysts and heterogeneous area , myometrial hypoechoic linear striations, diffuse vascularity and asymmetry of the myometrial w l [30,31].”
BackgroundTheories on the Pathogenesis of Endometriosis
Nap, A. W. (2011) · Wiley eBooks · doi:10.1002/9781444398519.ch5 · Cited by 33
Dantas-Vieira, G. C., da Silva, J. A. C., Padilha, R. T., & Magalhães-Padilha, D. M. (2020) · Research Society and Development · doi:10.33448/rsd-v9i10.9128 · Cited by 32
Xue, J., Zhang, H., Liu, W. Y., Liu, M., Shi, M., Wen, Z., & Li, C. (2013) · Reproduction · doi:10.1530/rep-13-0135 · Cited by 31
Ultrasound assessment of the peri‐implantation uterus: a review
Abdallah, Y., Naji, O., Saso, S., Pexsters, A., Stalder, C. M., Sur, S. D., Raine‐Fenning, N., Timmerman, D., Brosens, J. J., & Bourne, T. (2011) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.10098 · Cited by 34
da Silva, C. M., Belo, A. V., Andrade, S. P., Campos, P. P., Ferreira, M. C. F., Filho, A. L. D. S., & Carneiro, M. M. (2014) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2014.08.005 · Cited by 32
How to Evaluate Adenomyosis in Patients Affected by Endometriosis?
Donato, N. D., & Seracchioli, R. (2014) · Minimally Invasive Surgery · doi:10.1155/2014/507230 · Cited by 32
“It is known as a histological diagnosis but it has a clinical dignity showing symptoms (dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility) and sharing some pathogenic mechanisms with endometriosis [1].”
BackgroundZhai, J., Li, S., Sen, S., Vallvé-Juanico, J., Irwin, J. C., Vo, K. C., Wan, J., Du, Y., Chen, Z., & Giudice, L. C. (2022) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2022.05.007 · Cited by 30
“caused by uterine surgery, or physiologic through microtissue injury and repair (TIAR) after each menstrual cycle (Leyendecker et al., 2009).”
BackgroundInfluentialAdenomyosis: A Challenge in Clinical Gynecology
Cockerham, A. Z. (2012) · Journal of Midwifery & Women s Health · doi:10.1111/j.1542-2011.2011.00117.x · Cited by 31
Adenomyosis and female fertility: A critical review of the evidence
Sunkara, S. K., & Khan, K. S. (2012) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443615.2011.624208 · Cited by 30
Habiba, M. A., Benagiano, G., & Guo, S. (2023) · Biomolecules · doi:10.3390/biom13060975 · Cited by 31
“[5,6], who wrote that given the high prevalence of endometriosis and adenomyosis and the apparent lack of a “causal event” leading to hyperperistalsis, “it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life leads to the same extent of micro-traumatization”.”
BackgroundGonadotrophin-releasing hormone analogues and endometriosis: current strategies and new insights
Hashim, H. A. (2012) · Gynecological Endocrinology · doi:10.3109/09513590.2011.650751 · Cited by 29
“impaired endogenous GnRH II-mediated cytostatic regulation leading to an increase in uterine contraction or phases of hyperperistalsis at the endometrial–myometrial interface near the fundo-cornual raphe, inducing microtraumatizations with the activation of the mechanism of “tissue injury and repair” (TIAR) with subse…”
Adenomyosis and its impact on women fertility.
Garavaglia, E., Serafini, A., Inversetti, A., Stefano, F., Tandoi, I., Corti, L., & Candiani, M. (2015) · PubMed Central · Cited by 32
Canis, M. J., Bourdel, N., Houlle, C., Grémeau, A.-S., Botchorishvili, R., & Matsuzaki, S. (2017) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2016.12.008 · Cited by 27
“Two authors previously reported the role of trauma in the etiology of endometriosis [76,79,80,116,156,157].”
BackgroundWölfler, M. M., Küppers, M., Rath, W. H., Buck, V. U., Meinhold-Heerlein, I. M., & Classen-Linke, I. (2016) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2016.03.004 · Cited by 30
Dior, U. P., Nisbet, D., Fung, J. N., Foster, G., Healey, M., Montgomery, G. W., Rogers, P. A. W., Holdsworth‐Carson, S. J., & Girling, J. E. (2018) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2018.09.780 · Cited by 28
HLA-G is upregulated in advanced endometriosis
Rached, M. R., Coelho, V. P. C. V., Marin, M. L. C., Pincerato, K. M., Fujita, A., Kalil, J. E., & Abrão, M. S. (2019) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2019.01.030 · Cited by 27
Rees, C. O., van Vliet, H., Siebers, A. G., Bulten, J., Huppelschoten, A. G., Westerhuis, M. E. M. H., Mischi, M., & Schoot, B. C. (2022) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2022.12.013 · Cited by 27
The human periconceptional maternal-embryonic space in health and disease
Moreno, I., Capalbo, A., Mas, A., Garrido‐Gómez, T., Rosón, B., Poli, M., Dimitriadis, E., Santamaría, X., Vilella, F., & Simón, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00050.2021 · Cited by 32
Donnez, J., Donnez, O., Tourniaire, J., Brethous, M., Bestel, E., Garner, E. I. O., Charpentier, S., Humberstone, A., & Loumaye, E. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10245794 · Cited by 28
“The first and foremost involves invagination of the endometrial basalis, hyperestrogenism, hyperperistalsis, and tissue injury and repair (TIAR) activation [21,22].”
BackgroundUltrastructural features of endometrial-myometrial interface and its alteration in adenomyosis.
Zhang, Y., Zhou, L., Li, T. C., Duan, H., Yu, P., & Wang, H. Y. (2014) · Europe PMC (PubMed Central) · Cited by 27
Interdisciplinary S2k Guidelines for the Diagnosis and Treatment of Endometriosis
Ulrich, U. A., Buchweitz, O., Greb, R. R., Keckstein, J., von Leffern, I., Oppelt, P., Renner, S. P., Sillem, M., Stummvoll, W., & Schweppe, K.-W. (2013) · Geburtshilfe und Frauenheilkunde · doi:10.1055/s-0033-1350810 · Cited by 26
Revisiting the wandering womb: Oxytocin in endometriosis and bipolar disorder
Dinsdale, N. L., & Crespi, B. J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.09.005 · Cited by 27
“…the endometrium, requires a balance between cellular proliferation and apoptosis; this balance is dysregulated in endometriosis uteri, resulting in a state of chronic inflammation that is maintained by estrogen production in endometriosis lesions (Kobayashi et al., 2013; Leyendecker et al., 2009).”
BackgroundInfluentialTetikkurt, S., �elik, E., Solak, H. T., Çay, T., Isık, S., & Usta, A. T. (2018) · Molecular and Clinical Oncology · doi:10.3892/mco.2018.1660 · Cited by 25
“…they suggested that the non-pregnant uterus appear to impose a significant chronic mechanical strain on the subendometrial stromal cells that may lead to local inflammation and proliferation of the basal endometrium into the uterine wall, with the ensuing development of adenomyotic lesions (22,23).”
Kobayashi, H., Imanaka, S., Yoshimoto, C., Matsubara, S., & Shigetomi, H. (2024) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.16089 · Cited by 26
“The initial adhesion of endometrial tissue to the peritoneal surface may induce inflammation and local estrogen production via tissue injury and repair (TIAR) mechanisms 17 (Figure 3).”
Maclean, A., Barzilova, V., Patel, S., Bates, F., & Hapangama, D. K. (2023) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2023.103925 · Cited by 24
Relationship between adenomyosis and uterine polyps
Indraccolo, U., & Barbieri, F. (2011) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2011.02.014 · Cited by 26
“Exaggerating TIAR could lead [37] to the onset of both adenomyosis and endometriosis.”
BackgroundKrüger, K., Gilly, L., Niedobitek-Kreuter, G., Mpinou, L., & Ebert, A. D. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.02.019 · Cited by 21
“Endometriosis is a disease of the uterus in which implants of endometriotic tissue consisting of hormone-dependent glandular formations, stromal cells and smooth muscle are present outside the uterine cavity [1–6].”
BackgroundHuman Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor
Li, Y., Zou, S., Xia, X., & Zhang, S. (2014) · Reproductive Sciences · doi:10.1177/1933719114561559 · Cited by 23
Mansouri, R., Santos, X. M., Bercaw‐Pratt, J. L., & Dietrich, J. E. (2014) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2014.12.009 · Cited by 23
Supporting and Inhibiting Factors When Coping with Endometriosis From the Patientsʼ Perspective
Kundu, S., Wildgrube, J., Schippert, C., Hillemanns, P., & Brandes, I. (2015) · Geburtshilfe und Frauenheilkunde · doi:10.1055/s-0035-1546052 · Cited by 34
Kobayashi, H. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20043762 · Cited by 22
“, showing that inner myometrial injury is a result of repetitive microtrauma induced by estrogen, leading to endometrial invagination and adenomyosis development [9].”
BackgroundAre Adenomyosis and Endometriosis Phenotypes of the Same Disease Process?
Habiba, M. A., Guo, S., & Benagiano, G. (2023) · Biomolecules · doi:10.3390/biom14010032 · Cited by 28
“We also examined the Tissue Injury and Repair (TIAR) theory [4,5], which suggests that adenomyosis and endometriosis are two phenotypes of the same disease, and concluded that the theory is yet to be convincingly articulated [2].”
MethodWang, S., Duan, H., Zhang, Y., & Sun, F. (2015) · Reproductive Sciences · doi:10.1177/1933719115602764 · Cited by 23
“uterine transport capacity.(8,10) However, so far, the specific mechanisms that account for the link between estradiol-related uterine hyperperistalsis and ADS are poorly understood.”
BackgroundRasmussen, C. K., Hansen, E. S., & Dueholm, M. (2018) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13484 · Cited by 23
Clinicopathological features of different subtypes in adenomyosis: Focus on early lesions
Kobayashi, H., Matsubara, S., & Imanaka, S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254147 · Cited by 21
Analysis of in vivo uterine peristalsis in the non-pregnant female mouse
Zhang, Y., Qian, J., Zaltzhendler, O., Bshara, M., Jaffa, A. J., Grisaru, D., Duan, E., & Elad, D. (2019) · Interface Focus · doi:10.1098/rsfs.2018.0082 · Cited by 21
Kay, N., Huang, C., Shiu, L., Yu, Y.-C., Chang, Y., Schatz, F., Suen, J., Tsai, E., & Huang, S.-T. J. (2020) · Reproductive Sciences · doi:10.1007/s43032-020-00308-1 · Cited by 20
Long, X., Weiyuan, Z., Ping, J., Anxia, W., & Zhou, L. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.04.008 · Cited by 20
Alson, S., Jokubkiene, L., Hénic, E., & Sladkevicius, P. (2024) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.14812 · Cited by 20
Valdés‐Bango, M., Ros, C., Daza, M., Rius, M., Gràcia, M., Martínez‐Zamora, M. Á., de Guirior, C., Quintas, L., & Carmona, F. (2024) · Human Reproduction · doi:10.1093/humrep/deae105 · Cited by 19
Altered VEGF, Bcl-2 and IDH1 expression in patients with adenomyosis
Yalaza, C., Canacankatan, N., Gürses, İ., Aytan, H., & Taşdelen, B. (2020) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-020-05742-9 · Cited by 19
Unveiling the Pathogenesis of Adenomyosis through Animal Models
Wang, X., Benagiano, G., Liu, X., & Guo, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11061744 · Cited by 19
Wu, X., Sun, X., Zhao, C., Zhang, J.-Q., Wang, X., Zhang, A.-H., & Wang, X.-J. (2019) · RSC Advances · doi:10.1039/c9ra03525g · Cited by 18
Aas‐Eng, M. K., Montanari, E., Lieng, M., Keckstein, J., & Hudelist, G. (2020) · Seminars in Reproductive Medicine · doi:10.1055/s-0040-1718740 · Cited by 18
The First Lugano Workshop on the role of adenomyosis in ART
Cozzolino, M., Bulun, S. E., de Ziegler, D., Exacoustós, C., Fatemi, H. M., García-Velasco, J. A., Horne, A. W., Petraglia, F., Santulli, P., Somigliana, E., et al. (2024) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2024.104444 · Cited by 17
Obstetric Outcome After Surgical Treatment of Endometriosis: A Review of the Literature
Mooney, S. S., Ross, V., Stern, C. J., Rogers, P. A. W., & Healey, M. (2021) · Frontiers in Reproductive Health · doi:10.3389/frph.2021.750750 · Cited by 18
Molecular Targets for Nonhormonal Treatment Based on a Multistep Process of Adenomyosis Development
Kobayashi, H. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-01036-4 · Cited by 17
“Adenomyosis may develop from tissue injury, inflammation, angiogenesis, or tissue remodeling in the myometrium [8, 15], but the underlying regulatory mechanisms at each step remain unknown.”
BackgroundInfluentialAnemia-Associated Platelets and Plasma Prothrombin Time Increase in Patients with Adenomyosis
Lin, Q., Li, T., Ding, S., Yu, Q., & Zhang, X. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11154382 · Cited by 17
The Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis
Guo, S. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12030842 · Cited by 17
“One important foundation of the invagination theory is the tissue injury and repair (TIAR) hypothesis, proposed by Leyendecker and his associates [61,62], which postulates that injury induced by uterine hyperperistalsis/dysperistalsis causes”
Neurotrophin Expression Is Not Affected in Uteri of Women with Adenomyosis
Barcena, M. L., Wagner, M. F., Oldeweme, J., Arnold, J., Ebert, A. D., Schneider, A., & Mechsner, S. (2012) · Journal of Molecular Neuroscience · doi:10.1007/s12031-012-9757-x · Cited by 17
“The cause of this disease is still unknown, but it can occur after a uterine trauma, breaking through the barrier between the endometrium and myometrium (Leyendecker et al. 2009).”
BackgroundInfluentialAdenomyosis: Disease, uterine aging process leading to symptoms, or both?
Πρωτόπαπας, Α., Grimbizis, G., Athanasiou, S., & Loutradis, D. (2020) · PubMed Central · Cited by 17
L-22 enhances the invasiveness of endometrial stromal cells of adenomyosis in an autocrine manner.
Wang, Q., Wang, L., Shao, J., Wang, Y., Jin, L., Li, D., & Li, M. (2014) · PubMed Central · Cited by 17
Lingegowda, H., Miller, J. E., McCallion, A., Childs, T. J., Lessey, B. A., Koti, M., & Tayade, C. (2021) · F&S Science · doi:10.1016/j.xfss.2021.09.005 · Cited by 16
Harmsen, M. J., Arduç, A., Bleeker, M. C. G., Juffermans, L. J. M., Griffioen, A. W., Jordanova, E. S., & Huirne, J. A. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158434 · Cited by 19
“A theory for the involvement of angiogenesis in the pathogenesis of adenomyosis is that the repetitive nature of the contractions of the menstrual cycle causes tissue injury to the junctional zone, invagination of the endometrium in the myometrium, and leads to angiogenesis in the process of repair and establishment o…”
BackgroundExpression of tyrosine kinase receptor B in eutopic endometrium of women with adenomyosis
Huang, Y., Zheng, W., Mu, L., Ren, Y., Chen, X., & Liu, F. (2010) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-010-1718-4 · Cited by 15
“The theory named ‘‘tissue injury and repair’’ involving local estrogen production explained the physiological mechanism of endometriosis and adenomyosis [23] from a novel aspect.”
BackgroundHysteroscopic excision of symptomatic myometrial adenomyosis: feasibility and effectiveness
Xia, W., Zhang, D., Zhu, Q., et al. (2017) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.14673 · Cited by 16
Prathoomthong, S., Tingthanatikul, Y., Lertvikool, S., Rodratn, N., Waiyaput, W., Dittharot, K., Sroyraya, M., & Sophonsritsuk, A. (2018) · PubMed Central · doi:10.22074/ijfs.2018.5137 · Cited by 16
“These could activate T and B cells to produce antibodies and cytokines that may destroy the EMJZ (5).”
BackgroundInvestigation of the role of platelets in the aetiopathogenesis of adenomyosis
Mosele, S., Stratopoulou, C. A., Camboni, A., Donnez, J., & Dolmans, M. (2021) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2021.01.009 · Cited by 16
The Role of Abnormal Uterine Junction Zone in the Occurrence and Development of Adenomyosis
Xie, T., Xu, X., Yang, Y. L., Wu, C., Liu, X., Zhou, L., & Song, Y. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00684-2 · Cited by 16
Shang, W.-Q., Yu, J., Zhu, L., et al. (2015) · PubMed · Cited by 16
Single-cell RNA sequencing identifies the prolactin receptor as a therapeutic target in adenomyosis
Wang, R., Xu, S., Cui, Q., Chen, X., Wang, X., Liu, J., Liu, J., Xin, Y., Shen, H., Lv, F., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02339-z · Cited by 15
“15,16 Another theory proposes that adenomyosis results from the proliferation and differentiation of residual embryonic Müllerian ducts or adult stem cells within the myometrium.”
Ho, N.-T., Lin, S.-W., Lee, Y.-R., Tzeng, C., & Kao, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315328 · Cited by 16
“[41], in which tissue autotraumatization caused by malfunction of the junctional zone (JZ) initiates the TIAR process through activated estrogen receptors [42].”
BackgroundJin, Z., Wu, X., Liu, H., & Xu, C. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8580 · Cited by 15
“To date, two main theories have been proposed to explain the origin of adenomyosis: i) Invagination of the endometrial basalis as a result of the activation of tissue injury and repair mechanism; and ii) metaplasia of displaced embryonic pluripotent Mullerian remnants or differentiation of adult stem cells (3).”
Endométriose et génétique : les gènes sont-ils responsables de la maladie ?
Borghese, B., Vaiman, D., de Ziegler, D., & Chapron, C. (2010) · Journal de gynécologie, obstétrique et biologie de la reproduction. Supplément/Journal de gynécologie obstétrique et biologie de la reproduction · doi:10.1016/j.jgyn.2010.03.006 · Cited by 15
Zipponi, M., Cacciottola, L., & Dolmans, M. (2024) · Human Reproduction · doi:10.1093/humrep/deae116 · Cited by 14
Adenomyosis-associated infertility: an update of the immunological perspective
Cao, Y., Yang, D., Cai, S., Yang, L., Yu, S., Geng, Q., Mo, M., Li, W., Wei, Y., Li, Y., et al. (2024) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2024.104703 · Cited by 20
Hormonal contraceptives and endometriosis/adenomyosis
Schindler, A. E. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.534612 · Cited by 14
Expression and significance of ERβ and TrkB in endometriosis
Yu, X., Ren, H., Liu, T., Yong, M., & Zhong, H. (2016) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog2027.2016 · Cited by 14
Behavioural and neural responses to aversive visceral stimuli in women with primary dysmenorrhoea
Böttcher, B., Gizewski, E. R., Siedentopf, C., Steiger, R., Verius, M., Riedl, D., Ischebeck, A. K., Schmid, J., Wildt, L., & Elsenbruch, S. (2018) · European Journal of Pain · doi:10.1002/ejp.1302 · Cited by 14
Self-citationBoeer, B., Wallwiener, M., Rom, J., Schoenfisch, B., Brucker, S. Y., & Taran, F. (2014) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-013-3141-0 · Cited by 14
“As a frequently under diagnosed and overlooked problem, clinical symptoms of adenomyosis commonly include menorrhagia, painful menses and chronic pelvic pain [2–5].”
BackgroundDeep pelvic endometriosis: clinical features, diagnosis, and treatment - a comprehensive review
Abıke, F., Tanoğlu, F. B., & Sidar, G. (2025) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-025-08187-0 · Cited by 20
“Leyendecker et al. proposed a unifying theory based on the “tissue injury and repair” (TIAR) mechanism, in which repetitive uterine hyperperistalsis induces micro traumati-zation at the endometrial–myometrial interface, particularly at the fundo-cornual raphe [17].”
Acién, P., Velasco, I., & Acién, M. (2021) · BMC Women s Health · doi:10.1186/s12905-021-01347-9 · Cited by 15
“Dislocated basal endometrial fragments in the peritoneal cavity can now induce chronic inflammation and tissue injury and repair (TIAR) mechanisms, which activate local estrogen production, proliferation, and infiltrative growth leading to endometriosis [28].”
BackgroundSantin, A., Spedicati, B., Morgan, A., Lenarduzzi, S., Tesolin, P., Nardone, G. G., Mazzà, D., Lorenzo, G. D., Romano, F., Buonomo, F., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11082122 · Cited by 14
“extremely distressing symptoms may be overlooked, the disease is probably underdiagnosed, and the current estimates do not reflect the true prevalence of the disorder [3].”
Kato, K., Iriyama, T., Hara, K., Suzuki, K., Hashimoto, A., Sayama, S., Ichinose, M., Toshimitsu, M., Seyama, T., Sone, K., et al. (2023) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.15849 · Cited by 13
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
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