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
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“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
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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.”
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“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 201–300 of 415
Yahagi, N., Kobayashi, Y., Ohara, T., et al. (2011) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2010.01341.x · Cited by 13
“In endometriosis, tissue injury and repair occur, followed by infiltrative growth and chronic inflammation.(14) Although we could not find endometriosis tissue pathologically in the specimen because of heavy necrosis, in laparotomy, ovarian tumor was firmly attached to neighboring tissues that suggested endometriosis…”
BackgroundKissler, S., Marx, K., Scholtes, M. C. W., Pfeiffer, S., Meier, W., & Neulen, J. (2011) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2011.04.044 · Cited by 13
“The permanent hyperperistalsis continues like a selfperpetuation of the disease process [5].”
BackgroundMifepristone inhibited the expression of B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis
Qin, X., Sun, W., Wang, C., Li, M., Ζhao, X., Li, C., & Zhang, H. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00800-6 · Cited by 13
Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis
Shi, J., Jin, L., Leng, J., & Lang, J. (2016) · Chinese Medical Journal · doi:10.4103/0366-6999.173491 · Cited by 13
“Leyendecker et al.[9] suggested that such permanent hyperperistalsis might lead to microtraumatization with activation of mechanisms of tissue injury and repair in the local and basal endometrial layers resulting in AM.”
BackgroundThe role of nuclear factor-kappa-B p50 subunit in the development of endometriosis
Guo, S. (2010) · Frontiers in Bioscience-Elite · doi:10.2741/e272 · Cited by 12
Li, X., Gong, X., Zhu, L., Leng, J., Fan, Q., Sun, D., Lang, J., & Fan, Y. (2012) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.012060 · Cited by 12
Tanos, V., Balami, S., & Lingwood, L. (2019) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000572 · Cited by 12
Deep Infiltrating Endometriosis and Adenomyosis: Implications on Pregnancy and Outcome
Gruber, T. M., Ortlieb, L., Henrich, W., & Mechsner, S. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm11010157 · Cited by 11
“defined the concept of archimetrosis [7].”
BackgroundElsherbini, M., Koga, K., Hiraoka, T., Kumasawa, K., Maki, E., Satake, E., Taguchi, A., Makabe, T., Takeuchi, A., Izumi, G., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-22413-8 · Cited by 11
Prager, M., Wilson, T., Krüger, K., et al. (2011) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2011.08.723 · Cited by 11
Diagnostic Value of Circulating MicroRNAs for Endometriosis: a Meta-analysis
Zhou, L., Chen, Y., Gao, J., Shankar, S., & Zhang, G. (2020) · Reproductive Sciences · doi:10.1007/s43032-019-00024-5 · Cited by 10
Exosomes: potential diagnostic markers and drug carriers for adenomyosis
Cheng, W.-X., Wei, S., Zhou, Y., Shao, Y., & Li, M.-Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1216149 · Cited by 11
“Excessive peristalsis of the uterus causes destruction of the myometrium and facilitates invasion of the endometrial basalis cells, resulting in the formation of AM (Leyendecker et al., 2009; Leyendecker and Wildt, 2011) (Figure 3A).”
BackgroundSerum differential proteomic analysis of endometriosis and adenomyosis by iTRAQ technique
Long, X., Weiyuan, Z., Ping, J., Anxia, W., & Zhou, L. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.08.034 · Cited by 11
“Consequently, it may be contribute to the mechanism of pathology of endometriosis that hypoxia conditioning facilitates a large number of angiogenesis [10].”
BackgroundHuang, J., Duan, H., Wang, S., & Wang, Y. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.11976 · Cited by 11
In the mouse, prostaglandin D2 signalling protects the endometrium against adenomyosis
Philibert, P., Déjardin, S., Pirot, N., Pruvost, A., Nguyen, A. L., Bernex, F., Poulat, F., & Boizet‐Bonhoure, B. (2021) · Molecular Human Reproduction · doi:10.1093/molehr/gaab029 · Cited by 11
Co-expression of bone morphogenetic protein 6 with estrogen receptor a in endometriosis
Farfaras, A., Nonni, A., Effstratios, P., & Kassanos, D. P. (2011) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-011-2082-8 · Cited by 11
Adenomyosis and IVF/ICSI treatment: clinical considerations and recommendations
Dueholm, M., & Aagaard, J. (2018) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2018.1493923 · Cited by 11
Inflammatory Bowel Disease and Endometriosis: Diagnosis and Clinical Characteristics
Fiorillo, M., Neri, B., Mancone, R., Russo, C., Iacobini, F., Schiavone, S. C., Cristofaro, E. D., Migliozzi, S., Exacoustós, C., & Biancone, L. (2024) · Biomedicines · doi:10.3390/biomedicines12112521 · Cited by 10
“In a retrospective cross-sectional study including 781,571 adult women of which 6647 were diagnosed with endometriosis, 25,425 with fibromyalgia and 401 with both conditions, the association between endometriosis, fibromyalgia and IBD was assessed [86].”
Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk
Joachim, G. E., Bohnert, K. M., As‐Sanie, S., Harris, H. R., & Upson, K. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.01.035 · Cited by 9
Epithelial-to-mesenchymal transition in the development of adenomyosis
Huang, B., Tsai, H., Wang, P., Twu, N.-F., Yen, M., & Chen, Y. (2015) · Gynecology and Minimally Invasive Therapy · doi:10.1016/j.gmit.2015.05.002 · Cited by 10
Is adenomyosis a problem in reproduction and fertility?
Korzekwa, A. J., Łupicka, M., Socha, B. M., Mannelli, C., & Skarzynski, D. J. (2014) · Polish Journal of Veterinary Sciences · doi:10.2478/pjvs-2014-0028 · Cited by 12
“Leyendecker et al. (2009) hypothesized that adenomyosis may arise spontaneously from chronic peristaltic activity of the uterus or hyperperistalsis.”
Blood tests for prediction of deep endometriosis: A case-control study
Chen, Z., Zhang, L., Zhang, Y., Zhou, Y., Li, X., & Huang, X. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i35.10805 · Cited by 10
Chen, H., Wang, W., Wang, H., & Wang, X. (2022) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-022-04529-x · Cited by 10
The effect of unicornuate uterus on reproductive outcomes in infertile patients
Şımşek, E., Durdağ, G. D., Yağınç, D. A., et al. (2024) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2024.08.040 · Cited by 9
The effects of prolactin receptor blockade in a murine endometriosis interna model
Otto, C., Ulbrich, H., & Freiberg, C. (2022) · Pharmacology Research & Perspectives · doi:10.1002/prp2.916 · Cited by 9
Witkowski, M., Duliban, M., Rak, A., Profaska, M., Gurgul, A., Arent, Z., Gałuszka, A., & Kotula‐Balak, M. (2022) · Theriogenology · doi:10.1016/j.theriogenology.2022.06.015 · Cited by 9
Guo, Z., Duan, H., Wang, S., Wang, S., Lin, Q., & Li, Y. (2022) · BMC Women s Health · doi:10.1186/s12905-022-01871-2 · Cited by 9
“According to the theory of invagination, the local hyperestrogenic environment of the uterus leads to abnormal contraction of the myometrium and subsequent trauma to the endometrial–myometrial interface (EMI), which is also known as the uterine junction zone [8].”
BackgroundImproved nude mouse models for green fluorescence human endometriosis
Liu, B., Wang, N., Wang, Z., Hong, S., Li, J.-G., Ding, H., Pan, Q., Dong, Y., Zhou, C., & Zhuang, G. (2010) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2010.01345.x · Cited by 10
Benign Gynecologic Conditions of the Uterus
Kassam, Z., Petkovska, I., Wang, C. L., Trinh, A. M., & Kamaya, A. (2017) · Magnetic Resonance Imaging Clinics of North America · doi:10.1016/j.mric.2017.03.005 · Cited by 8
Is adenomyosis associated with the risk of endometrial cancer?
Gün, İ., Öner, Ö., Bodur, S., Özdamar, Ö., & Atay, V. (2012) · PubMed · Cited by 9
Evolutionäre Aspekte in der Pathogenese und Pathophysiologie von Adenomyose und Endometriose
LEYENDECKER, G., & Wildt, L. (2019) · Journal für Gynäkologische Endokrinologie/Österreich · doi:10.1007/s41974-019-00112-z · Cited by 9
Self-citationMatot, R., Blickstein, O., Leibner, G., Bar-Peled, U., Borovich, A., Geron, Y., Gilboa, Y., Krissi, H., & Perlman, S. (2025) · Journal of Ultrasound in Medicine · doi:10.1002/jum.16667 · Cited by 8
Li, Z., Li, X., Lin, M., Qiu, S., Wang, L., Lai, L., Luo, X., Mo, Z., Dong, G., Lyu, G., et al. (2022) · International Journal of Hyperthermia · doi:10.1080/02656736.2022.2131001 · Cited by 8
“Since the endometrium at the uterine fundus was more likely to invade the myometrium [24], one-third of the endometrium near the uterine fundus was selected for ablation in this study.”
MethodHuang, C.-Y., Wang, H.-I., Wang, P., et al. (2011) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2011.01.015 · Cited by 8
“Through decades of research, it has been suggested that there are multiple mechanisms, including an inflammatory process involving macrophages, several growth factors, cytokines,(22) thrombin,(23) and a circle of tissue injury and repair.(24) Despite not being a malignant disorder, endometriosis exhibits cellular prol…”
BackgroundMadendağ, Y., Şahin, E., Aydin, E., et al. (2017) · Gynecology Obstetrics and Reproductive Medicine · doi:10.21613/gorm.2017.716 · Cited by 8
“Either chronic uterine peristaltic activity or local micro- trauma caused by hyper peristaltic phase in the endometrial-myometrial interface activates the mechanism of tissue injury and repair (TIAR) (2).”
BackgroundInfluentialMelatonin: The First Noninvasive Causal Therapy for Both Endometriosis and Adenomyosis?
Tesařík, J. (2018) · Journal of Gynecology and Womens Health · doi:10.19080/jgwh.2018.12.555829 · Cited by 8
“In fact, the similarity of the respective pathophysiological mechanisms of endometriosis and adenomyosis [2] suggests that melatonin may also be useful to treat adenomyosis, another disease caused by aberrant behaviour of endometrial epithelial cells in response to 17β-estradiol.”
BackgroundJunctional zone thickening: an endo-myometrial unit disorder
Gordts, S., Grimbizis, G., Tanos, V., Koninckx, P. R., & Campo, R. (2023) · Facts Views and Vision in ObGyn · doi:10.52054/fvvo.15.4.109 · Cited by 8
Otto, C., Schkoldow, J., Krahl, E., Fuchs, I., & Ulbrich, H. (2011) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2011.425 · Cited by 8
“The tissue-injury and repair theory suggests that local hyperestrogenism in response to microtrau-matization at the endometrial-myometrial interface leads to enhanced uterine peristaltic activity within the endomyome-trial junctional zone (6).”
The clinical significance of classical and new emerging determinants of adenomyosis.
Bodur, S., Dündar, Ö., Pektas, M. K., et al. (2015) · PubMed · Cited by 8
Gora, S., Elad, D., & Jaffa, A. J. (2017) · Reproductive Sciences · doi:10.1177/1933719117697256 · Cited by 8
“It has been reported that any change in the rate and direction of uterine peristalsis compared to its typical characteristics may reduce the rate of take-home baby and even lead to infertility.(10,11) Objective methods to analyze TVUS video clips employed image processing methods to extract time changes in the boundar…”
MethodSun, T., Li, X., Shi, J., Wu, Y., Gu, Z., & Leng, J. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.696374 · Cited by 8
Hormonal Treatment for Severe Hydronephrosis Caused by Bladder Endometriosis
Efe, E., Bakacak, M., Serin, S., Koluş, E., Ercan, Ö., & Resim, S. (2014) · Case Reports in Urology · doi:10.1155/2014/891295 · Cited by 7
“Since the cells of endometriosis include estrogen and progesterone receptors, the disease responds to hormonal treatment [29, 30].”
Expression of CXCL12 and its receptor CXCR4 in patients with adenomyosis
Li, J., Yin, G., Chen, M., Yang, S., Wu, A., Liang, J., & Yuan, Z. (2017) · Oncology Letters · doi:10.3892/ol.2017.5762 · Cited by 7
“Although AD is a benign disease, the pathological progression, including cell adhesion, invasion, metastasis and recurrence, is similar to that in malignant tumors (14,15).”
Cao, Y., Wang, X., Liu, X., Harada, T., & Guo, S. (2022) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000012 · Cited by 7
“One important building block within the invagination theory hinges on the TIAR hypothesis, proposed by Leyendecker et al[12] and Leyendecker andWildt[13].”
BackgroundOppelt, P. G., Weber, M., Mueller, A., Boosz, A. S., Hoffmann, I., Raffel, N., Lotz, L., Beckmann, M. W., & Dittrich, R. (2018) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13428 · Cited by 7
Feng, D., Menger, M. D., Wang, H., & Laschke, M. W. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.013664 · Cited by 7
“Various theories have been postulated during the last decades (Viganò et al., 2004; Leyendecker et al., 2009; Maruyama and Yoshimura, 2012).”
BackgroundWang, S., Duan, H., Wang, S., Guo, Z., & Lin, Q. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10508-4 · Cited by 6
“EMI SMCs have reactive hyperplasia and hypertrophy, excessive proliferation, and disorder of cell arrangement, further enhancing the mechanical strain of the myometrium (Leyendecker et al. 2009; Leyendecker and Wildt 2011).”
Xholli, A., Molinari, F., Scovazzi, U., Londero, A. P., Perugi, I., Kratochwila, C., Cremonini, F., & Cagnacci, A. (2024) · ULTRASONOGRAPHY · doi:10.14366/usg.24117 · Cited by 8
“Such pain has also been linked to cervical stenosis [11] and an unfavorable uterine flexion angle [14-16], likely requiring stronger uterine contractions to overcome the obstruction of menstrual blood flow [17].”
BackgroundRamos, I. S., Caldeira, M. O., Poock, S. E., et al. (2024) · JDS Communications · doi:10.3168/jdsc.2024-0633 · Cited by 6
Anti-angiogenic therapy as potential treatment for adenomyosis
Harmsen, M. J., Juffermans, L. J. M., Kroon, M. O., Griffioen, A. W., & Huirne, J. A. F. (2025) · Angiogenesis · doi:10.1007/s10456-024-09960-6 · Cited by 7
“Theoretically, in humans each menstrual cycle induces tissue injury and repair, which together with elevated paracrine estrogen exposure, might lead to invagination of ectopic endometrium [38, 39].”
Vandermeulen, L., Cornelis, A., Rasmussen, C. K., et al. (2017) · PubMed · Cited by 6
Zhang, A., Liu, X., Wang, J., Deng, K., & Wang, J. (2021) · Twin Research and Human Genetics · doi:10.1017/thg.2021.11 · Cited by 6
“…epithelial cells (Received 20 November 2020; accepted 13 January 2021; First Published online 29 March 2021) Adenomyosis is regarded as one of most common gynecological disorders, which has a morbidity of 8–27% in women with reproductive age (Huang et al., 2015; Leyendecker et al., 2009).”
BackgroundCardiometabolic profiles in women with adenomyosis
Ateş, S., Aydın, S., & Özcan, P. (2022) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2022.2099256 · Cited by 6
“Since inflammation was also suggested to be implicated in the pathogenesis of adenomyosis (Leyendecker et al. 2009), it may be a possible factor in the elevated BP in patients with adenomyosis.”
BackgroundOta, Y., Ota, K., Takahashi, T., Morimoto, Y., SUZUKI, S., Sano, R., & Shiota, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11226707 · Cited by 6
“Ectopic endometrial tissue induces hypertrophy and hyperplasia of the surrounding myometrium, resulting in a diffusely enlarged uterus [2].”
BackgroundCould the Uterine Junctional Zone be Used to Identify Early-Stage Endometriosis in Women?
Tosti, C., Zupi, E., & Exacoustós, C. (2014) · Women s Health · doi:10.2217/whe.14.20 · Cited by 6
Biomarkers of endometriosis - current trends
Adamyan, L. V., & Aznaurova, Y. B. (2018) · Russian Journal of Human Reproduction · doi:10.17116/repro201824157-62 · Cited by 7
Ayas, S., Bayraktar, M., Gürbüz, A., Alkan, A., & Eren, S. (2012) · Balkan Medical Journal · doi:10.5152/balkanmedj.2012.042 · Cited by 6
Clinical and ultrasonological features of adenomyosis and its histopathological correlation
Gupta, S., Goel, G., Agrawal, S., Garg, P., & Khanuja, E. (2016) · International Journal of Reproduction Contraception Obstetrics and Gynecology · doi:10.18203/2320-1770.ijrcog20163158 · Cited by 5
Physiopathologie et anatomopathologie de l’endométriose
Petit, É. (2017) · Imagerie de la Femme · doi:10.1016/j.femme.2017.01.001 · Cited by 6
Khandeparkar, M. S., Jalkote, S., Panpalia, M. M., Nellore, S., Mehta, T., Ganesan, K., & Parikh, F. R. (2018) · Global Reproductive Health · doi:10.1097/grh.0000000000000014 · Cited by 6
“Alternative hypotheses include abnormal migration of the basal layer of the endometrium along the intramyometrial lymphatic channels or the presence of ectopic intramyomterial endometrial tissue which initiates a de novo metaplastic process in the uterine wall([8,9]).”
Correlation between Cyr61 expression and clinicopathologic parameters in adenomyosis
Zhang, D., Xia, W., Tong, T., Li, C., Shi, W., Yan, M., Xue, R., Guan, X., & Zhang, J. (2016) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2016.08.004 · Cited by 6
Smoking and endometriosis: A narrative review
Vallée, A., Féki, A., Josseran, L., & Ayoubi, J.-M. (2025) · Tobacco Induced Diseases · doi:10.18332/tid/203429 · Cited by 6
The Pathophysiology of Adenomyosis
Habiba, M. A., Benagiano, G., & Brosens, I. A. (2015) · Springer eBooks · doi:10.1007/978-3-319-13012-5_3 · Cited by 5
den Bosch, T. V., Votino, A., Cornelis, A., et al. (2016) · Gynecologic and Obstetric Investigation · doi:10.1159/000445072 · Cited by 5
Jin, T., Kyozuka, H., Fujimori, M., Nomura, S., Hakozaki, Y., Suzuki, D., & Nomura, Y. (2020) · FUKUSHIMA JOURNAL OF MEDICAL SCIENCE · doi:10.5387/fms.2021-02 · Cited by 5
“Adenomyosis is defined as the ectopic proliferation of endometrial glands and stroma within the myometrium of the uterus, which causes the uterus to become edematous and enlarged 1,2) .”
BackgroundRectal endometriosis presenting as toxic megacolon
Alvarado, L. E. R., Bahmad, H. F., Mejia, O., et al. (2021) · Autopsy and Case Reports · doi:10.4322/acr.2021.319 · Cited by 5
Guo, Z., Lin, Q., Chang, Y., et al. (2024) · Genomics · doi:10.1016/j.ygeno.2024.110877 · Cited by 5
Endometriosis – Pathogenesis, Diagnosis, and Therapeutic Options for Clinical and Ambulatory Care
Schweppe, K.-W., Rabe, T., Langhardt, M. A., Woziwodzki, J., Petraglia, F., & Kiesel, L. (2013) · Florence Research (University of Florence) · Cited by 6
Adenomyosis and Ultrasound: The Role of Ultrasound and Its Impact on Understanding the Disease
Exacoustós, C. (2015) · Springer eBooks · doi:10.1007/978-3-319-13012-5_9 · Cited by 5
Marzhevskay, V. V., Prisyazhnaya, T. S., Zhamoydik, V. I., Берлев, И. В., & Malek, A. V. (2018) · Journal of obstetrics and women s diseases · doi:10.17816/jowd67364-73 · Cited by 5
“[3], представляют веские аргументы в пользу имплан тационной теории.”
Endometriosezentren und Qualitätsmanagement
Schweppe, K.-W., Ebert, A. D., & Kiesel, L. (2010) · Der Gynäkologe · doi:10.1007/s00129-009-2484-x · Cited by 5
Adenomyotic glands are highly related to endometrial glands
Maier, V., Höll, M., Dietze, R., Mecha, E. O., Omwandho, C. O. A., Tinneberg, H., Meinhold-Heerlein, I. M., & Konrad, L. (2019) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2019.11.007 · Cited by 5
Yang, J., Li, X., Yu, P. E. N. G., Sun, Z., Zhang, L., Duan, J., & Zhong, N. A. (2026) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.71129 · Cited by 4
“While historically described as ‘endometriosis in-terna’ [2], adenomyosis is now recognised as a distinct entity originating from the dysfunction of the endometrial–myome-trial interface (EMI), also known as the archimetra or junctional zone (JZ) [3, 4].”
InfluentialDemirtaş, G. S., & Uyar, İ. (2021) · Archives of Iranian Medicine · doi:10.34172/aim.2021.54 · Cited by 4
Organoids as a model to study the human endometrium
Li, J., Lin, L., Zhong, J., Li, X., Lee, C., & Chiu, P. C. N. (2022) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000040 · Cited by 5
Wu, R., Zeng, L., Hu, Q., Qu, X., He, F., Bao, J., Wei, W., Zhang, W., Dai, W., Li, H., et al. (2023) · Human Fertility · doi:10.1080/14647273.2023.2260102 · Cited by 5
“…refers to a situation where the lesion invades the myometrium extensively and results in diffusive enlargement of the uterus with histological features demonstrating that the ectopic endometrial tissue induces hypertrophy and hyperplasia of the surrounding myometrium (Leyendecker et al., 2009).”
BackgroundEstablishment of an immortalized cell line derived from human adenomyosis ectopic lesions
Wang, Z., Cui, F., Chen, Y., Liu, H., Zhang, Y., Shi, Y., Zhang, Y., Wang, Y., Liang, N., Xu, L., et al. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102284 · Cited by 4
Gupta, S., Harlev, A., Agarwal, A. K., & Pandithurai, E. (2015) · SpringerBriefs in reproductive biology · doi:10.1007/978-3-319-18308-4_3 · Cited by 5
Otsubo, Y., Nishida, M., Arai, Y., et al. (2016) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443615.2016.1157685 · Cited by 4
“Affected patients can be classified into two categories; focal adenomyosis, with lesions localised in a specific uterine wall, and diffuse adenomyosis, with lesions involving the entire uterus (Leyendecker et al. 2009).”
BackgroundUterine Peristalsis and the Development of Endometriosis and Adenomyosis
LEYENDECKER, G., & Wildt, L. (2011) · Wiley eBooks · doi:10.1002/9781444398519.ch20 · Cited by 4
Self-citationMagnetic resonance imaging presentation of diffuse and focal adenomyosis before and after pregnancy
Marcellin, L., LEGAY, L., Santulli, P., Millischer, A., Bordonné, C., Maitrot‐Mantelet, L., Maignien, C., Bourdon, M., Gaudet-Chardonnet, A., Borghese, B., et al. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.02.008 · Cited by 3
Updates on adenomyosis and fertility
Shats, M., Zajicek, M., Siedhoff, M. T., & Meyer, R. (2025) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000001039 · Cited by 3
Medical Treatment for Endometriosis: One Size Does Not Fit All
Vercellini, P., Salmeri, N., Bandini, V., Conca, B., Viganò, P., Somigliana, E., & Vignali, M. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15062408 · Cited by 3
“Leyendecker et al. stated that “the aetiology of endometriosis is primarily the aetiology of adenomyosis” [51].”
Che, J., Gao, Y., Sun, M., Zhou, S., Lu, P., & Zhao, T. (2022) · Journal of Ultrasound in Medicine · doi:10.1002/jum.16168 · Cited by 3
Role of benign ovarian cysts in the development of adenomyosis
Alam, S., Ahmad, S., Khan, M. M., Nasir, S., Sharif, N., Ziaullah, S., Khalid, A., & Rauf, F. (2016) · Saudi Medical Journal · doi:10.15537/smj.2016.9.13599 · Cited by 3
Ryntz, T., & Lobo, R. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-65399-2.00035-8 · Cited by 3
Endometriose: Pathogenese, Symptome und Diagnostik
Mechsner, S. (2015) · Springer eBooks · doi:10.1007/978-3-662-43669-1_5 · Cited by 3
Mulyantoro, I., Indrapraja, O., Widjiati, W., & Noerpramana, N. P. (2020) · Journal of Biomedicine and Translational Research · doi:10.14710/jbtr.v6i2.8113 · Cited by 3
“Oestrogen is thought to function through the MAPK and PI3K/AKT/mTOR pathways, thus, increasing the likelihood of targeting the PI3K pathway is likely to be a new approach for the treatment of endometriosis.(14,15) Metformin (1,1-dimethylbiguanide hydrochepatic lipaseoride) is an oral anti-diabetic drug that has been r…”
MethodEndometriosis-associated Pain in Patients with and without Hormone Therapy
Brandes, I., Neuser, M., Köpf, A., Chiàntera, V., Sehouli, J., & Mechsner, S. (2017) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/jeppd.5000286 · Cited by 3
“The leading symptom of endometriosis is dysmenorrhea, which generally has a very early onset – often before a girl’s first period (8, 9).”
BackgroundExploring endometriosis through 3D in vitro models: A narrative review
Juli, C., Nyang’au, E. M., Götte, M., & von Versen‐Höynck, F. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103032 · Cited by 3
“…routes of pathogenesis linked to aberrant cell differentiation [7,8], the tissue injury and repair hypothesis and the denervation-reinnervation theory are based on tissue damage and subsequent endometrial tissue release linked to mechanical activity such as hyperperistalsis of the uterus [9,10].”
Maclean, A., Johnson, E., Rushworth, C., Hill, C. J., Caamaño‐Gutiérrez, E., & Hapangama, D. K. (2026) · Science Advances · doi:10.1126/sciadv.aea6379 · Cited by 4
Infiltrating Adenomyosis of the Cervix With Features of a Low-grade Stromal Sarcoma
Chen, X., Hamele‐Bena, D., Galic, V., et al. (2014) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0b013e31829673bf · Cited by 2
“At present, the most commonly accepted theory for adenomyosis is the invasion of endometrial glands and stroma into the myometrium resulting from fissures formed during tissue injury and repair (9).”
BackgroundCharacteristic and Regenerative Potential of Human Endometrial Stem Cells and Progenitors
Ghamari, A., Daghigh, F., Mohebbi, A., Rahimi, Y., Shojaie, L., & Zolbin, M. M. (2021) · Springer eBooks · doi:10.1007/978-981-16-0301-3_3 · Cited by 2
Physiopathologie de l’adénomyose : une énigme non résolue
Bourdon, M., Santulli, P., Marcellin, L., Maignien, C., Maitrot‐Mantelet, L., & Chapron, C. (2021) · Gynécologie Obstétrique Fertilité & Sénologie · doi:10.1016/j.gofs.2021.10.005 · Cited by 2
Boizet‐Bonhoure, B., Déjardin, S., Girard, M., Durix, Q., Poulat, F., & Philibert, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042003 · Cited by 2
“Their etiology remains uncertain; however, both have similar symptoms (pelvic pain, heavy menstrual bleeding, and dysmenorrhea) and contribute to fertility disorders [4].”
BackgroundOccult clear cell carcinoma arising from oxidative stress‑exposed cystic adenomyosis: A case report
Hoshiba, N., Kayahashi, K., Hayashi, S., Nomura, S., Nakayama, M., Iizuka, T., & Fujiwara, H. (2024) · Molecular and Clinical Oncology · doi:10.3892/mco.2024.2748 · Cited by 2
“In adenomyosis, high levels of estrogen can stimulate peristalsis of the muscle fibers of the myometrium, causing stress in the endometrial‑myometrial junctional zone (9,10).”
BackgroundEndometriosis and adenomyosis – a shared pathophysiology
LEYENDECKER, G., Wildt, L., & Mall, G. (2010) · CNR Solar (Scientific Open-access Literature Archive and Repository) (Consiglio Nazionale delle Ricerche) · Cited by 2
Self-citationImagerie des pathologies gynécologiques de l’adolescente
Bazot, M., Jarboui, L., Dechoux, S., Morel, A., & Thomassin‐Naggara, I. (2013) · Imagerie de la Femme · doi:10.1016/j.femme.2013.02.008 · Cited by 2
LEYENDECKER, G., & Wildt, L. (2011) · Springer eBooks · doi:10.1007/978-3-642-15012-8_9 · Cited by 2
Self-citationInteraktion in der Arzt-Patientinnen-Beziehung beim Krankheitsbild Endometriose
Esterl, M. (2016) · Psychotherapie Forum · doi:10.1007/s00729-015-0058-z · Cited by 2
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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