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.
Overview
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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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Claims the paper makes
40 Not checked yet · 23 Own interpretation · 2 No basis given
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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The 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
plain- Asserted: passes — The authors put it forward as true.
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None 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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In 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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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 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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None 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
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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None 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
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- Based: unclear — It is unclear why the paper says it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It 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.”
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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.”
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
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
What we know about primary dysmenorrhea today: a critical review.
Iacovides, S., Avidon, I., & Baker, F. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv039 · Cited by 973
“…have recently proposed that the high intrauterine pressure, peristalsis, and myometrial contractions that account for primary dysmenorrheic pain, result in mechanical strain and injury of the uterus, and ultimately, may drive the development of adenomyosis (Leyendecker et al., 2009, 2015).”
BackgroundEndometriosis and infertility: pathophysiology and management
de Ziegler, D., Borghese, B., & Chapron, C. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60490-4 · Cited by 853
Endometrial stem/progenitor cells: the first 10 years
Gargett, C. E., Schwab, K. E., & Deane, J. A. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv051 · Cited by 561
“Theories suggest that chronic microtrauma to the JZ from chronic peristaltic myometrial contractions causes repeated cycles of tissue injury and repair (Leyendecker et al., 2009).”
BackgroundThe Pathogenesis of Endometriosis: Molecular and Cell Biology Insights
Laganà, A. S., Garzon, S., Götte, M., Viganò, P., Franchi, M. P., Ghezzi, F., & Martin, D. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225615 · Cited by 503
“At the same time, when women with symptomatic endometriosis are compared with women without or minimal disease, the differences were reported not only at the level of endometriosis implants but even at the level of eutopic endometrium [66], uterus [67], and peritoneal environment [68].”
BackgroundPathogenesis of endometriosis: The genetic/epigenetic theory
Koninckx, P. R., Ussia, A., Adamyan, L., Wattiez, A., Gomel, V., & Martin, D. C. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.10.013 · Cited by 427
“Interestingly, microtraumas are also observed in the endometrial-myometrial JZ (239), which is consistent with the Archimetra theory (265, 266).”
Diagnosing adenomyosis: an integrated clinical and imaging approach
Chapron, C., Vannuccini, S., Santulli, P., Abrão, M. S., Carmona, F., Fraser, I. S., Gordts, S., Guo, S., Just, P., Noël, J., et al. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmz049 · Cited by 439
Macrophage and Fibroblast Interactions in Biomaterial‐Mediated Fibrosis
Witherel, C. E., Abebayehu, D., Barker, T. H., & Spiller, K. L. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801451 · Cited by 374
Adult stem cells in the endometrium
Gargett, C. E., & Masuda, H. (2010) · Molecular Human Reproduction · doi:10.1093/molehr/gaq061 · Cited by 361
Pathogenesis of uterine adenomyosis, invagination or metaplasia?
García-Solares, J., Donnez, J., Donnez, O., & Dolmans, M.-M. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.12.030 · Cited by 339
Bazot, M., & Daraï, É. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.01.024 · Cited by 332
Pathogenesis of adenomyosis, an update on molecular mechanisms
Vannuccini, S., Tosti, C., Carmona, F., Huang, S. J., Chapron, C., Guo, S.-W., & Petraglia, F. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2017.06.016 · Cited by 326
“Chronic peristaltic myometrial contractions induce microtrauma to the JZ, causing a vicious cycle in which local oestrogen production, COX-2 mediated (Chen et al., 2010a), promotes uterine peristalsis and further auto-traumatization (Gargett et al., 2016; Leyendecker et al., 2009).”
Chapron, C., Tosti, C., Marcellin, L., Bourdon, M., Lafay-Pillet, M.-C., Millischer, A.-E., Streuli, I., Borghese, B., Petraglia, F., & Santulli, P. (2017) · Human Reproduction · doi:10.1093/humrep/dex088 · Cited by 294
Adenomyosis: Mechanisms and Pathogenesis
Zhai, J., Vannuccini, S., Petraglia, F., & Giudice, L. C. (2020) · Seminars in Reproductive Medicine · doi:10.1055/s-0040-1716687 · Cited by 331
Leyendecker, G., Bilgicyildirim, A., Inacker, M., Stalf, T., Huppert, P., Mall, G., Böttcher, B., & Wildt, L. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-014-3437-8 · Cited by 261
“larly pertain to anovulatory cycles, such as follicular persistency with high estradiol levels in blood and presumably long-lasting hyperperistalsis [7].”
BackgroundMethodInfluentialSelf-citationImaging for the evaluation of endometriosis and adenomyosis
Exacoustós, C., Manganaro, L., & Zupi, E. (2014) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2014.04.010 · Cited by 258
“The cause of adenomyosis is unknown, but interesting theories have considered adenomyosis a pathology of the endo-myometrial junctional zone, and have attempted to explain the association of adenomyosis with subfertility and endometriosis [73,74].”
BackgroundInfluentialStructural and molecular features of the endomyometrium in endometriosis and adenomyosis
Benagiano, G., Brosens, I., & Habiba, M. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmt052 · Cited by 246
“Leyendecker et al. (2009) proposed abnormal peristalsis as a unifyinghypothesis foradenomyosis, aswell asendometriosis.”
BackgroundBiomarkers in endometriosis: Challenges and opportunities
Ahn, S. H., Singh, V., & Tayade, C. (2017) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.01.009 · Cited by 242
Pathogenesis of deep endometriosis
Gordts, S., Koninckx, P., & Brosens, I. (2017) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.08.036 · Cited by 241
Exacoustós, C., Brienza, L., Giovanni, A. D., Szabolcs, B., Romanini, M. E., Zupi, E., & Arduini, D. (2010) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.8900 · Cited by 241
Upson, K., & Missmer, S. A. (2020) · Seminars in Reproductive Medicine · doi:10.1055/s-0040-1718920 · Cited by 264
“2017;96(6):715–726 [PubMed: 28556124] 10.”
InfluentialZhang, Q., Duan, J., Liu, X., & Guo, S.-W. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.015 · Cited by 211
Pathogenesis of Endometriosis: The Origin of Pain and Subfertility
Gruber, T. M., & Mechsner, S. (2021) · Cells · doi:10.3390/cells10061381 · Cited by 237
“Their uterus has up to two decades to turn an inherently good functionality into a self-destructive force before reproduction is aspired to [72].”
BackgroundAdenomyosis pathogenesis: insights from next-generation sequencing
Bulun, S. E., Yıldız, Ş., Adli, M., & Wei, J. (2021) · Human Reproduction Update · doi:10.1093/humupd/dmab017 · Cited by 216
“This view resonates with the involvement of tissue injury and repair as a mechanism for adenomyosis (Leyendecker et al., 2009).”
BackgroundThe pathophysiology of uterine adenomyosis: an update
Benagiano, G., Habiba, M. A., & Brosens, I. A. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.06.044 · Cited by 187
Molecular and Cellular Pathogenesis of Endometriosis
Klemmt, P. A. B., & Starzinski‐Powitz, A. (2017) · Current Women s Health Reviews · doi:10.2174/1573404813666170306163448 · Cited by 182
“Leyendecker and colleagues proposed a new concept of tissue injury and repair mechanism (TIAR) (reviewed in [52, 53]) to explain a common pathophysiology of adenomyosis and endometriosis development.”
BackgroundUterine bleeding: how understanding endometrial physiology underpins menstrual health
Jain, V., Chodankar, R. R., Maybin, J. A., & Critchley, H. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00629-4 · Cited by 206
Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis
Cousins, F. L., O, D. F., & Gargett, C. E. (2018) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2018.01.011 · Cited by 158
The Pathogenesis of Adenomyosis vis-à-vis Endometriosis
Guo, S.-W. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020485 · Cited by 165
“Moreover, there is a remarkable similarity between hyperestrogenism in adenomyosis and the role of estrogen in wound repair [29,30].”
BackgroundInfluentialPrevalence of adenomyosis in women undergoing surgery for endometriosis
Donato, N. D., Montanari, G., Benfenati, A., Leonardi, D., Bertoldo, V., Monti, G., Raimondo, D., & Seracchioli, R. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.08.016 · Cited by 157
Zhang, Q., Duan, J., Olson, M., Fazleabas, A., & Guo, S.-W. (2016) · Reproductive Sciences · doi:10.1177/1933719116641763 · Cited by 149
“The prevailing view appears to be that they originate either from the metaplasia of the ‘‘second Müllerian system’’ or, more likely, from the basal layer of the endometrium with stem cell features that were regurgitated through the fallopian tubes because of dysperistalsis.(20,39,40) Nonetheless, there are no data tha…”
Martínez-Conejero, J. A., Morgan, M., Montesinos, M., Fortuño, S., Meseguer, M., Simón, C., Horcajadas, J. A., & Pellicer, A. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.07.1088 · Cited by 155
A new concept of endometriosis and adenomyosis, tissue injury and repair (TIAR)
Leyendecker, G., & Wildt, L. (2011) · hmbci · doi:10.1515/hmbci.2011.002 · Cited by 147
“(From Leyendecker et al. Arch Gynecol Obstet 2009;280: 529–38, with permission w9x.) cular fibers and fibroblasts.”
BackgroundSelf-citationImpact of endometriosis on quality of life, anxiety, and depression: an Austrian perspective
Friedl, F., Riedl, D., Fessler, S., Wildt, L., Walter, M. H., Richter, R., Schüßler, G., & Böttcher, B. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-015-3789-8 · Cited by 145
“4 years [2]; the etiology is not completely understood [3, 4].”
BackgroundSelf-citationTaniguchi, F. (2011) · Frontiers in Bioscience · doi:10.2741/e277 · Cited by 141
“The tissue injury and repair theory suggests that local production of estrogens by ectopic endometrial tissue results in infiltration of basal endometrium into the myometrium and the peritoneal cavity, and eventually leads to the development of endometriosis (2).”
BackgroundN-cadherin identifies human endometrial epithelial progenitor cells by in vitro stem cell assays
Nguyen, H. P. T., Xiao, L. Y., Deane, J. A., Tan, K.-S., Cousins, F. L., Masuda, H., Sprung, C. N., Rosamilia, A., & Gargett, C. E. (2017) · Human Reproduction · doi:10.1093/humrep/dex289 · Cited by 145
Lazzeri, L., Di Giovanni, A., Exacoustos, C., Tosti, C., Pinzauti, S., Malzoni, M., Petraglia, F., & Zupi, E. (2014) · Reproductive Sciences · doi:10.1177/1933719114522520 · Cited by 137
“Adenomyosis is known as an histological diagnosis but it has a clinical dignity showing symptoms (dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility) and sharing some pathogenic mechanisms with endometriosis.(5) Established imaging criteria may support an accurate diagnosis of adenomyosis.”
BackgroundHarmsen, M. J., Wong, C. F. C., Mijatovic, V., Griffioen, A. W., Groenman, F. A., Hehenkamp, W. J. K., & Huirne, J. A. F. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz024 · Cited by 146
Exacoustós, C., Morosetti, G., Conway, F., Camilli, S., Martire, F. G., Lazzeri, L., Piccione, E., & Zupi, E. (2019) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2019.09.788 · Cited by 135
Risks of adverse pregnancy outcome in endometriosis
Brosens, I., Brosens, J. J., Fusi, L., Al-Sabbagh, M., Kuroda, K., & Benagiano, G. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.02.024 · Cited by 132
Kuijsters, N. P. M., Methorst, W., Kortenhorst, M. S. Q., Rabotti, C., Mischi, M., & Schoot, B. C. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2017.03.019 · Cited by 131
“This rise in oestradiol possibly leads to hypercontractility of the subendometrial myometrium (Leyendecker et al., 2009).”
BackgroundGuo, S.-W. (2018) · Human Reproduction · doi:10.1093/humrep/dey015 · Cited by 116
Conservative Surgery for Adenomyosis and Results: A Systematic Review
Younes, G., & Tulandi, T. (2017) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2017.07.014 · Cited by 116
“The ectopic endometrial tissue induces hypertrophy and hyperplasia of the 52 surrounding myometrium, resulting in a diffusely enlarged uterus (12).”
BackgroundCurrent Medical Therapy for Adenomyosis: From Bench to Bedside
Etrusco, A., Barra, F., Chiàntera, V., Ferrero, S., Bogliolo, S., Evangelisti, G., Oral, E., Pastore, M., Izzotti, A., Venezia, R., et al. (2023) · Drugs · doi:10.1007/s40265-023-01957-7 · Cited by 125
“Adenomyosis is frequently associated with endometriosis [8, 9].”
Endometriosis and pregnancy complications: a Danish cohort study
Glavind, M. T., Forman, A., Arendt, L. H., Nielsen, K. B., & Henriksen, T. B. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.09.020 · Cited by 112
Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†
AlAshqar, A., Reschke, L. D., Kirschen, G. W., & Borahay, M. A. (2021) · Biology of Reproduction · doi:10.1093/biolre/ioab054 · Cited by 127
“Aromatase and StAR upregulation is mediated by COX-2, and the locally overproduced estrogen induces ERβ overexpression, which alongside ERα, stimulates local angiogenesis and endometrial proliferation (Figure 4) [24].”
BackgroundLazzeri, L., Morosetti, G., Centini, G., Monti, G., Zupi, E., Piccione, E., & Exacoustós, C. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.06.031 · Cited by 108
Global Transcriptome Abnormalities of the Eutopic Endometrium from Women with Adenomyosis
Herndon, C. N., Aghajanova, L., Balayan, S., Erikson, D., Barragan, F., Goldfien, G., Vo, K. C., Hawkins, S., & Giudice, L. C. (2016) · Reproductive Sciences · doi:10.1177/1933719116650758 · Cited by 106
“Leyendecker et al postulated that ectopic diseases of the endometrium result in part from the physiological mechanism of ‘‘tissue injury and repair’’ involving local estrogen production in an estrogen-sensitive environment.(25) Activity of aromatase and estrone sulfatase has been identified in both eutopic and ectopic…”
BackgroundBiomechanics of the human uterus
Myers, K. M., & Elad, D. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1388 · Cited by 101
“The new hypothesis of ‘tissue injury and repair’ (TIAR) relates the origin of these diseases to hyperperistaltic activity of the uterus.(87,193,194) It has been assumed that increased and sustained uterine peristalsis during early periods of reproductive life induce IUP waves that result in increased mechanical strain…”
BackgroundTreatment of adenomyomectomy in women with severe uterine adenomyosis using a novel technique
Saremi, A. T., Bahrami, H., Salehian, P., hakak, N., & Pooladi, A. (2014) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2014.02.008 · Cited by 107
“The ectopic endometrial tissue appears to induce hypertrophy and hyperplasia of the surrounding myometrium, resulting in a diffusely enlarged uterus (Leyendecker et al., 2009; Taran et al., 2010).”
BackgroundAdenomyosis and Infertility—Review of Medical and Surgical Approaches
Szubert, M., Koziróg, E., Olszak, O., Krygier-Kurz, K., Kaźmierczak, J., & Wilczyński, J. R. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031235 · Cited by 99
“concerns ’auto-traumatisation’ of the uterus which leads to the TIAR (Tissue Injury And Repair) mechanism as the main cause of adenomyosis [10].”
BackgroundThe uterine junctional zone: a 3-dimensional ultrasound study of patients with endometriosis
Exacoustós, C., Luciano, D. E., Corbett, B., Felice, G. D., Feliciantonio, M. D., Luciano, A. A., & Zupi, E. (2013) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2013.06.006 · Cited by 96
“They have also been linked to dysmenorrhea and menorrhagia and may play a role in the pathogenesis of endometriosis by facilitating retrograde menstruation and implantation of viable endometrial cells into the abdominal cavity.(6,16,17) Pelvic endometriosis,”
BackgroundTargeting oxidative stress to treat endometriosis
Harlev, A., Gupta, S., & Agarwal, A. K. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2015.1077226 · Cited by 92
“This auto-traumatization would enable the implantation of the endometrium in the peritoneal cavity [31].”
BackgroundCharacterization of endometriosis-associated immune cell infiltrates (EMaICI)
Scheerer, C., Bauer, P., Chiàntera, V., Sehouli, J., Kaufmann, A. M., & Mechsner, S. (2016) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-016-4142-6 · Cited by 88
“These theories were followed by the model of ‘‘tissue injury and repair’’ (TIAR) with permanent increased paracrine estrogen action [5].”
MethodMüllerianosis: Four Developmental (Embryonic) Müllerian Diseases
Batt, R. E., & Yeh, J. (2013) · Reproductive Sciences · doi:10.1177/1933719112472736 · Cited by 88
“Leyendecker et al point out that ‘‘the specific orientation of the circular fibers of the archimyometrium results from the fusion of the two paramesonephric ducts forming a fundocornual raphe in the midline,’’ an anatomical observation that supports their TIAR hypothesis for the pathogenesis of acquired adenomyosis.(6…”
BackgroundBernuit, D., Ebert, A. D., Halis, G., Strothmann, A., Gerlinger, C., Geppert, K., & Faustmann, T. (2011) · Journal of Endometriosis · doi:10.5301/je.2011.8525 · Cited by 83
Pathogenesis and malignant transformation of adenomyosis (Review)
Koike, N., Tsunemi, T., Uekuri, C., Akasaka, J., Ito, F., 重光, 愛., & Kobayashi, H. (2012) · Oncology Reports · doi:10.3892/or.2012.2184 · Cited by 81
“These data suggest that myometrial hypertrophy is a response/reaction of the ectopic endometrial cells to the surrounding tissue, which shares characteristics with physiological and pathological mechanisms of wound healing (tissue injury and repair) (1,19,20).”
Contemporary evaluation of women and girls with abnormal uterine bleeding: FIGO Systems 1 and 2
Jain, V., Munro, M. G., & Critchley, H. (2023) · International Journal of Gynecology & Obstetrics · doi:10.1002/ijgo.14946 · Cited by 93
Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology
Guo, S. (2022) · Reproduction · doi:10.1530/rep-22-0224 · Cited by 93
National German Guideline (S2k): Guideline 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., Wilde, R. L. D., et al. (2014) · Geburtshilfe und Frauenheilkunde · doi:10.1055/s-0034-1383187 · Cited by 75
An update on the pharmacological management of adenomyosis
Streuli, I., Dubuisson, J. B., Santulli, P., de Ziegler, D., Batteux, F., & Chapron, C. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.953055 · Cited by 75
“There are few studies suggesting that dysperistaltism could also be implicated in the pathogenesis and symptoms associated with adenomyosis [21].”
BackgroundMetabolomics reveals perturbations in endometrium and serum of minimal and mild endometriosis
Dutta, M., Singh, B. K., Joshi, M. V., Das, D., Subramani, E., Maan, M., Jana, S. K., Sharma, U., Das, S., Dasgupta, S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-23954-7 · Cited by 75
A Look at Uterine Wound Healing Through a Histopathological Study of Uterine Scars
Roeder, H., Cramer, S. F., & Leppert, P. C. (2012) · Reproductive Sciences · doi:10.1177/1933719111426603 · Cited by 74
“For example, it has been suggested that adenomyosis and endometriosis may be initiated by the inflammatory response in healing wounds that occur during the menstrual cycle.(7) Furthermore, of interest, there are molecular similarities between fibroids and keloids.”
BackgroundPhenotypic characterization of adenomyosis occurring at the inner and outer myometrium
Kishi, Y., Shimada, K., Fujii, T., Uchiyama, T., Yoshimoto, C., Konishi, N., Ohbayashi, C., & Kobayashi, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189522 · Cited by 74
Prevalence of adenomyosis in women with subfertility: systematic review and meta‐analysis
Mishra, I., Melo, P., Easter, C., Sephton, V., Dhillon‐Smith, R. K., & Coomarasamy, A. (2023) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.26159 · Cited by 85
A Lifelong Impact on Endometriosis: Pathophysiology and Pharmacological Treatment
Chen, L.-H., Lo, W.-C., Huang, H.-Y., & Wu, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087503 · Cited by 94
The Diagnosis and Treatment of Deep Infiltrating Endometriosis
Halis, G., Mechsner, S., & Ebert, A. D. (2010) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2010.0446 · Cited by 72
Mechsner, S., Grum, B., Gericke, C., Loddenkemper, C., Dudenhausen, J. W., & Ebert, A. D. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.03.015 · Cited by 72
“The OT-OTR system may, therefore, be involved in the process of contractility regulation of the nonpregnant uterus in humans (13, 26, 28, 29, 32), marmoset monkeys (31), and mice (33).”
BackgroundFaserl, K., Golderer, G., Kremser, L., Lindner, H. H., Sarg, B., Wildt, L., & Seeber, B. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1532 · Cited by 71
Self-citationPathogenesis of Human Adenomyosis: Current Understanding and Its Association with Infertility
Khan, K. N., Fujishita, A., & Mori, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144057 · Cited by 77
“In addition, the TIAR mechanism can be activated in response to tissue auto-traumatization [60,67].”
BackgroundInfluentialLiu, X., Nie, J., & Guo, S. (2010) · Human Reproduction · doi:10.1093/humrep/deq311 · Cited by 68
“Indeed, it has been proposed recently that both endometriosis and adenomyosis may result from tissue injury and repair (Leyendecker et al., 2009).”
BackgroundRelationship between adenomyosis and endometriosis; Different phenotypes of a single disease?
Maruyama, S., Imanaka, S., Nagayasu, M., Kimura, M., & Kobayashi, H. (2020) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2020.08.019 · Cited by 67
“If tight physiological regulation fails to clear the prolonged activation of ReTIAR/EMID, a vicious circle is formed between uterine contraction and aberrant estrogen production, promoting the further development of adenomyosis [7,15,35].”
BackgroundBurghaus, S., Schäfer, S. D., Beckmann, M. W., Brandes, I., Brünahl, C., Chvatal, R., Drahoňovský, J., Dudek, W., Ebert, A. D., Fahlbusch, C., et al. (2021) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-1380-3693 · Cited by 69
“, implantation theory [1], coelom metaplasia theory [2], archimetra or “tissue injury and repair concept” [3, 4], but without finding a satisfactory final explanation.”
BackgroundInfluentialEndometriosis, a modern syndrome.
Brosens, I. A., & Benagiano, G. (2011) · PubMed Central · Cited by 68
Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far
Stratopoulou, C. A., Donnez, J., & Dolmans, M. (2020) · Reproductive Sciences · doi:10.1007/s43032-020-00361-w · Cited by 69
Barcena, M. L., Gericke, J., Reichelt, U., Okuducu, A. F., Ebert, A. D., Chiàntera, V., Schneider, A., & Mechsner, S. (2011) · Human Reproduction · doi:10.1093/humrep/der253 · Cited by 69
“…PSMC. ow nloaded from https://academ ic.oup.com /hum rep/article-abstract/26/10/2721/610614 by guest on 20 O ctober 2018 to the peritoneum and differentiate into a ‘miniature-uterus’ by a metaplastic process (De Snoo, 1942; Leyendecker et al., 2002; Mechsner et al., 2005; Leyendecker et al., 2009).”
BackgroundInfluentialUltrasound Findings of Adenomyosis in Adolescents: Type and Grade of the Disease
Exacoustós, C., Lazzeri, L., Martire, F. G., Russo, C., Martone, S., Centini, G., Piccione, E., & Zupi, E. (2021) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2021.08.023 · Cited by 65
Mao, X., Wang, Y., Carter, A. V., Zhen, X., & Guo, S. (2011) · Reproductive Sciences · doi:10.1177/1933719111404610 · Cited by 63
“Leyendecker and his colleagues proposed that uterine dysperistalsis and hyperperistalsis may cause ‘‘microtraumatization’’ that leads to adenomyosis.(13) Indeed, adenomyosis has been shown to have ultrastructural features of altered contractility in myometrium,(14) and oxytocin receptor (OTR) has been shown to be over…”
BackgroundYavuzcan, A., Çağlar, M., Üstün, Y., Dilbaz, S., Özdemir, İ., Yıldız, E., Özkara, A., & Kumru, S. (2013) · Journal of the Turkish-German Gynecological Association · doi:10.5152/jtgga.2013.55452 · Cited by 63
Stejskalová, A., Fincke, V. E., Nowak, M. K., Schmidt, Y., Borrmann, K., von Wahlde, M., Schäfer, S. D., Kiesel, L., Greve, B., & Götte, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-83645-8 · Cited by 58
Yamaguchi, A., Kyozuka, H., Fujimori, K., Hosoya, M., Yasumura, S., Yokoyama, T., Satô, A., Hashimoto, K., & The Japan Environment and Children's Study Group (2018) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13498 · Cited by 60
The known, the unknown and the future of the pathophysiology of endometriosis
Ochoa Bernal, M. A., & Fazleabas, A. T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115815 · Cited by 59
“Estrogen, in addition, could act as positive feedback, causing the self-perpetuation of the disease, allowing the endometrial tissue to implant outside the uterine cavity [34].”
BackgroundGonadotropin-releasing hormone antagonist (linzagolix): A new therapy for uterine adenomyosis
Donnez, O., & Donnez, J. (2020) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.04.017 · Cited by 58
In vitro and in vivo ocular biocompatibility of electrospun poly(ɛ-caprolactone) nanofibers
da Silva, G. R., de Lima, T. H., Oréfice, R. L., Fernandes-Cunha, G. M., Silva‐Cunha, A., Zhao, M., & Béhar‐Cohen, F. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.03.003 · Cited by 58
Endometriosis and adenomyosis: Similarities and differences
Donnez, J., Stratopoulou, C. A., & Dolmans, M.-M. (2024) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2023.102432 · Cited by 57
Location-dependent value of pelvic MRI in the preoperative diagnosis of endometriosis
Krüger, K., Behrendt, K., Niedobitek-Kreuter, G., Koltermann, K. C., & Ebert, A. D. (2013) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2013.02.007 · Cited by 57
Yen, C., Huang, S.-T. J., Lee, C., Wang, H., & Liao, S. (2017) · Reproductive Sciences · doi:10.1177/1933719117691141 · Cited by 57
Tempest, N., Hill, C. J., Maclean, A., Marston, K., Powell, S. G., Al‐Lamee, H., & Hapangama, D. K. (2021) · Human Reproduction Update · doi:10.1093/humupd/dmab039 · Cited by 60
“A number of human and experimental studies support the theory of invagination of the endometrial basalis into the myometrium through a process of tissue injury and repair (Leyendecker et al., 2009; Leyendecker and Wildt, 2011; Vannuccini et al., 2017; Yamaguchi et al., 2021).”
ResultAn update on adenomyosis in the adolescent
Dietrich, J. E. (2010) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e32833cefaf · Cited by 55
Ibrahim, M. G., Chiàntera, V., Frangini, S., Younes, S., Köhler, C., TAUBE, E. T., Plendl, J., & Mechsner, S. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.09.002 · Cited by 52
Guo, J. H., Chen, L., Luo, N., Li, C., Chen, R., Qu, X., Liu, M., Kang, L., & Cheng, Z. (2016) · Scientific Reports · doi:10.1038/srep21416 · Cited by 53
Ibrahim, M. G., Sillem, M., Plendl, J., Chiantera, V., Sehouli, J., & Mechsner, S. (2017) · Reproductive Sciences · doi:10.1177/1933719116687855 · Cited by 52
“All specimens were retrieved from the presumed area of maximal shearing stress at the EMJZ.”
BackgroundMethodInfluentialHong, I. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.89795 · Cited by 58
Qi, S., Ζhao, X., Li, M., Zhang, X., Lu, Z., Yang, C., Zhang, C., Zhang, H., & Zhang, N. (2015) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-015-0084-2 · Cited by 52
“Although adenomyosis is a benign disease, it exhibits a series of biological behaviours that are similar to those of malignant tumours, including adhesion, invasion, and implantation [26].”
BackgroundDevelopment of a clinical prediction model for diagnosing adenomyosis
Tellum, T., Nygaard, S., Skovholt, E. K., Qvigstad, E., & Lieng, M. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.06.009 · Cited by 49
Carbone, M. G., Campo, G., Papaleo, E., Marazziti, D., & Maremmani, I. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081616 · Cited by 53
Vercellini, P., Bandini, V., Viganò, P., Stefano, G. D., Merli, C. E. M., & Somigliana, E. (2023) · Human Reproduction · doi:10.1093/humrep/dead229 · Cited by 50
Qi, S., Yan, L., Liu, Z., et al. (2018) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-018-0375-5 · Cited by 46
“Although endometriosis is a benign disease, it exhibits a series of biological behaviors similar to malignant tumors, including adhesion, invasion, and implantation [28].”
BackgroundGandini, S., Lazzeroni, M., Peccatori, F. A., Bendinelli, B., Saieva, C., Palli, D., Masala, G., & Caini, S. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.12.009 · Cited by 46
Metabolomics in endometriosis: challenges and perspectives for future studies
Ortiz, C. N., Torres-Reverón, A., & Appleyard, C. B. (2021) · Reproduction and Fertility · doi:10.1530/raf-20-0047 · Cited by 50
Distinct types of uterine adenomyosis based on laparoscopic and histopathologic criteria
Pistofidis, G. A., Makrakis, E., Koukoura, O., Bardis, N. S., Balinakos, P. M., & Anaf, V. (2014) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog16152014 · Cited by 44
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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