The DOI matches its Crossref record; 267 of the 290 references it cites were found in a registry or an index; none of the 83 sources its claims cite is checked for support yet.
Pathogenesis of endometriosis: the genetic/epigenetic theory
Open accessAbstract
OBJECTIVE To study the pathophysiology of endometriosis. DESIGN Overview of observations on endometriosis. SETTING Not applicable. PATIENT(S) None. INTERVENTIONS(S) None. MAIN OUTCOME MEASURE(S) The hypothesis is compatible with all observations. RESULT(S) Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases. CONCLUSION(S) The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Koninckx proposes a polygenetic/polyepigenetic theory in which inherited and acquired genetic/epigenetic incidents explain endometriosis predisposition, heterogeneity, and progression from subtle lesions to typical, cystic, or deep disease. The theory is argued to be compatible with all observations, but it remains speculative and untested.
Key findings
- Endometriosis is hereditary: risk is 6%–9% higher in first-degree relatives and 15% higher when relatives had severe disease; hereditary factors are estimated to account for 50% of endometriosis. GWAS identified 10 or 15 loci, and a meta-analysis identified five loci regulating sex steroid hormone pathways, five secondary signals, and 19 SNPs robustly associated with endometriosis.
- The genetic/epigenetic theory holds that genetic and epigenetic incidents transmitted at birth explain predisposition and endometriosis-associated changes in endometrium, immunology, and placentation; additional transmissible incidents in a cell—ranging from endometrial to stem cells—are required for typical, cystic ovarian, or deep lesions. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur.
- Typical cystic ovarian and deep endometriosis lesions are heterogeneous and represent three different diseases; lesions are clonal in origin. Deep endometriosis lesions are generally unique, larger than 1 cm, with some 20% lymph node involvement; depth distribution shows two populations overlapping at 6 mm, and a >5 mm definition was later suggested.
- Natural history is described as mostly non-progressive: most subtle lesions do not progress, most typical/cystic/deep lesions are not progressive after diagnosis, and most are not recurrent after surgery. Cystic ovarian endometriosis recurrence after stripping is less than 20% within 6 months; recurrence of deep endometriosis after complete excision is rare.
Methods
- Design: overview of observations on endometriosis; setting not applicable; no patients and no interventions. Main outcome measure: the hypothesis is compatible with all observations.
- Data: clinical, histologic, and biochemical observations and research on endometriotic tissues; the paper notes there is no nonhuman animal model with sufficient similarity to human myometrium, junctional zone, endometrium, placentation, and pregnancy disorders.
- Analysis: narrative synthesis of observations and historical theories—Sampson’s retrograde menstruation/implantation, metaplasia, and the endometriotic disease theory—into a polygenetic/polyepigenetic mechanism, with figures and a table summarizing clinical observations.
Limitations
- The paper states the theory “will remain a theory until disproven by new observations”; it can only speculate what combination of genetic and epigenetic incidents leads to typical, cystic, deep, or extragenital endometriosis, and redundancy of biologic processes can mask phenotypic effects.
- The paper states that absence of experimentation limits views to clinical, histologic, and biochemical observations; natural history is unclear, progression of subtle lesions or from typical to cystic/deep lesions has not been observed directly, epidemiology is unclear, and recurrence data are limited. Some cited observations are personal or unpublished.
- Evident from the text: this is a narrative hypothesis paper with no new primary data, no systematic review or meta-analysis, and no formal experimental test of the proposed mechanism.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 83 cited sources checked · 0 supported · 0 flagged
In the paper
“Recurrence rates of deep endometriosis lesions after complete excision are rare (personal observations) (60).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [60] Ianieri, 2018, Recurrence in deep infiltrating endometriosis: a systematic review of the literature, J Minim Invasive Gynecol source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The risk of developing endometriosis is 6%-9% higher in first-degree relatives of women with endometriosis (34,35)”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“A recent meta-analysis identified five loci regulating sex steroid hormone pathways, five secondary signals, and 19 single-nucleotide polymorphisms robustly associated with endometriosis (54)”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [54] Sapkota, 2017, Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism, Nat Commun source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis lesions are clonal, as demonstrated for typical (149), deep (150), and cystic ovarian (151-153) endometriosis.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [149] Wu, 2003, Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay, Fertil Steril source
- Not checked yetcites [150] Mayr, 2003, Does endometriosis really have premalignant potential? A clonal analysis of laser-microdissected tissue, FASEB J source
- Not checked yetcites [151] Tamura, 1998, Analysis of clonality in human endometriotic cysts based on evaluation of X chromosome inactivation in archival formalin-fixed, paraffin-embedded tissue, Lab Invest
- Not checked yetcites [152] Yano, 1999, Molecular analysis of clonality in ovarian endometrial cysts, Gynecol Obstet Invest source
- Not checked yetcites [153] Jimbo, 1997, Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts, Am J Pathol
Load-bearingStrength:boosted· 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
“Endometriosis is a hereditary disease.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“and 15% higher when they had severe disease (36,37).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [36] Kennedy, 1998, The genetics of endometriosis, J Reprod Med
- Not checked yetcites [37] Kennedy, 1998, Magnetic resonance imaging to assess familial risk in relatives of women with endometriosis, Lancet source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In the endometrium of women with endometriosis several hundred minor biochemical changes have been described (124-128).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [124] Carvalho, 2011, Role of eutopic endometrium in pelvic endometriosis, J Minim Invasive Gynecol source
- Not checked yetcites [125] Lessey, 2013, Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects, Semin Reprod Med source
- Not checked yetcites [126] Herndon, 2016, Global transcriptome abnormalities of the eutopic endometrium from women with adenomyosis, Reprod Sci source
- Not checked yetcites [127] Lagana, 2016, Natural killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner, Arch Gynecol Obstet source
- Not checked yetcites [128] da Costa e Silva Rde, 2016, Estrogen signaling in the proliferative endometrium: implications in endometriosis, Rev Assoc Med Bras (1992) source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“More recently, hereditary factors were estimated to account for 50% of endometriosis (45)(46)(47).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [45] Sapkota, 2015, Genetic burden associated with varying degrees of disease severity in endometriosis, Mol Hum Reprod source
- Not checked yetcites [46] Saha, 2015, The heritability of endometriosis, Fertil Steril source
- Not checked yetcites [47] Baranov, 2015, Systems genetics view of endometriosis: a common complex disorder, Eur J Obstet Gynecol Reprod Biol source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis seems associated with a higher risk of cancer, as recently reviewed (139, 140).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [139] Lim, 2018, Type and risk of cancer related to endometriosis: ovarian cancer and beyond, BJOG source
- Not checked yetcites [140] Dawson, 2018, Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development, Ecancermedicalscience source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In addition, regression of smaller lesions is common (57).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [57] Evers, 2013, Is adolescent endometriosis a progressive disease that needs to be diagnosed and treated?, Hum Reprod source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 20
- It may state two separate claims as one. 24
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most deep endometriosis lesions do not (or very slowly) progress over time, but some lesions can be fast progressive (unpublished observations).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Although most women with deep endometriosis have severe pain, especially during menstruation (65), some large lesions (estimated to be 5%) are not painful.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [65] Koninckx, 1996, Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration, Fertil Steril source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Subtle endometriosis lesions decrease with age, whereas typical, cystic, and deep lesions increase with age, at least until menopause (58).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [58] Koninckx, 2016, Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review, Gynaecol Surg source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
“Endometriosis has a variable appearance.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Recurrence rates of cystic ovarian endometriosis after stripping are less than 20% within 6 months (61, 62) but vary with the surgeon (63) and the technique used.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [61] Busacca, 1999, Recurrence of ovarian endometrioma after laparoscopic excision, Am J Obstet Gynecol source
- Not checked yetcites [62] Moscarini, 2014, Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate, Arch Gynecol Obstet source
- Not checked yetcites [63] Muzii, 2011, The singer, not the song, J Minim Invasive Gynecol 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis is associated with higher concentrations of Escherichia coli in menstrual blood (134, 135), with vaginal infections (136), and with chronic endometritis (137).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [134] Khan, 2010, Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis, Fertil Steril source
- Not checked yetcites [135] Khan, 2018, Bacterial contamination hypothesis: a new concept in endometriosis, Reprod Med Biol source
- Not checked yetcites [136] Lin, 2016, Increased risk of endometriosis in patients with lower genital tract infection: a nationwide cohort study, Medicine (Baltimore) source
- Not checked yetcites [137] Cicinelli, 2017, Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link, Fertil Steril 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
“That the low natural killer (NK) cell activity in plasma remains low whereas the elevated CA-125 concentrations return to normal after surgical excision of deep endometriosis suggests that the NK cell defect is a cause and the elevated CA-125 a consequence of endometriosis (89).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OTHER OBSERVATIONS ASSOCIATED WITH ENDOMETRIOSIS
What the sources say
- Not checked yetcites [89] Oosterlynck, 1994, CO2-laser excision of endometriosis does not improve the decreased natural killer activity, Acta Obstet Gynecol Scand source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Cystic ovarian endometriosis causes pain in more than 80%, and deep endometriosis causes severe pain in the large majority of women (27).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OTHER OBSERVATIONS ASSOCIATED WITH ENDOMETRIOSIS
What the sources say
- Not checked yetcites [27] Koninckx, 1991, Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain, Fertil Steril source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis, especially cystic ovarian and deep endometriosis (130, 131), and adenomyosis (132, 133) are associated with abnormal placentation, insufficient physiologic changes in the spiral arteries, and an increased risk of preterm birth, small for gestational age (SGA) babies, and preeclampsia (131).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [130] Pan, 2017, Risk of gestational hypertension-preeclampsia in women with preceding endometriosis: a nationwide population-based study, PLoS One source
- Not checked yetcites [131] Koninckx, 2018, Endometriosis and pregnancy outcome, Fertil Steril source
- Not checked yetcites [132] Hasdemir, 2016, The role of adenomyosis in the pathogenesis of preeclampsia, Geburtshilfe Frauenheilkd source
- Not checked yetcites [133] Hashimoto, 2018, Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition, J Matern Fetal Neonatal Med 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Genomewide association studies identified 10 (50) or 15 (51) loci with single-nucleotide polymorphisms (52) associated with severe endometriosis, but located in DNA sequences regulating target genes (53).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [50] Rahmioglu, 2015, Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci, Hum Mol Genet source
- Not checked yetcites [51] Fung, 2018, Genetics of endometriosis: state of the art on genetic risk factors for endometriosis, Best Pract Res Clin Obstet Gynaecol source
- Not checked yetcites [52] Matalliotakis, 2017, The role of gene polymorphisms in endometriosis, Mol Med Rep 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.
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
“Endometriosis is a heterogeneous disease.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Estrogens stimulate growth, whereas progestogen therapy and pregnancy stop growth or cause decidualization and decrease endometriosis-associated pain.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Clinical observations suggest that the prevalence and severity of deep endometriosis have markedly increased during the past 20 years (58).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [58] Koninckx, 2016, Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review, Gynaecol Surg source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, progression of subtle lesions or progression from typical to cystic or deep lesions has not been observed directly (56).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > OBSERVATIONS IN ENDOMETRIOSIS
What the sources say
- Not checked yetcites [56] Canis, 2016, Endometriosis may not be a chronic disease: an alternative theory offering more optimistic prospects for our patients, Fertil Steril source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“The clinical consequence is that lesions vary, that occasional lesions can be rapidly progressive, and that the effect of medical therapy can be variable between patients.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
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
“If, on the contrary, metaplasia indicates stable and transmissible genetic or epigenetic changes, this comes close to the genetic/epigenetic theory.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > THE PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY Historical Background
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. 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
“Typical, cystic, and deep lesions are benign tumors, which after an initial period of rapid growth stop growing or progress slowly and which do not recur after complete excision.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, we recently realized the association of endometriosis with vaginal and pelvic infection (78, 136, 138) and the presence of an important metabolome in the uterine and peritoneal cavities.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
What the sources say
- Not checked yetcites [78] Kobayashi, 2014, Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation, Mol Med Rep source
- Not checked yetcites [136] Lin, 2016, Increased risk of endometriosis in patients with lower genital tract infection: a nationwide cohort study, Medicine (Baltimore) source
- Not checked yetcites [138] Heidarpour, 2017, Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis, J Obstet Gynaecol Res 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.
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
“However, these defects might also explain the associated subfertility, with monthly fecundity rates below 10% being similar to women with unexplained infertility, the associated changes in the endometrium, and the associated pregnancy problems.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The endometriotic disease theory (EDT) postulated (246) that genetic incidents are required for the development of typical, cystic, or deep endometriosis.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
What the sources say
- Not checked yetcites [246] Koninckx, 1999, Implantation versus infiltration: the Sampson versus the endometriotic disease theory, Gynecol Obstet Invest source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“Subtle or microscopic lesions will progress to more severe lesions only if additional incidents happen.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
Tests✓ 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
“Local estrogen production (154) and progesterone resistance (155-162) were demonstrated in larger endometriosis lesions (154-163)”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [154] Bulun, 2015, Molecular biology of endometriosis: from aromatase to genomic abnormalities, Semin Reprod Med source
- Not checked yetcites [155] Bulun, 2006, Progesterone resistance in endometriosis: link to failure to metabolize estradiol, Mol Cell Endocrinol source
- Not checked yetcites [156] Wang, 2009, Endometriosis is associated with progesterone resistance in the baboon (Papio anubis) oviduct: evidence based on the localization of oviductal glycoprotein 1 (OVGP1), Biol Reprod source
- Not checked yetcites [157] Bruner-Tran, 2010, Dioxin and endometrial progesterone resistance, Semin Reprod Med source
- Not checked yetcites [158] Bulun, 2010, 17β-Hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis, Semin Reprod Med source
- Not checked yetcites [159] Al-Sabbagh, 2012, Mechanisms of endometrial progesterone resistance, Mol Cell Endocrinol source
- Not checked yetcites [160] Barragan, 2016, Human endometrial fibroblasts derived from mesenchymal progenitors inherit progesterone resistance and acquire an inflammatory phenotype in the endometrial niche in endometriosis, Biol Reprod source
- Not checked yetcites [161] Joshi, 2017, Progesterone resistance in endometriosis is modulated by the altered expression of microRNA-29c and FKBP4, J Clin Endocrinol Metab
- Not checked yetcites [162] Patel, 2017, Progesterone resistance in endometriosis: origins, consequences and interventions, Acta Obstet Gynecol Scand source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Incidents also occur in lesions, and a clonal origin does not exclude heterogeneity within a lesion as demonstrated for breast (257) and other (258, 259) cancers.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
What the sources say
- Not checked yetcites [257] Geyer, 2010, Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas, J Pathol source
- Not checked yetcites [258] Dagogo-Jack, 2018, Tumour heterogeneity and resistance to cancer therapies, Nat Rev Clin Oncol source
- Not checked yetcites [259] McGranahan, 2017, Clonal heterogeneity and tumor evolution: past, present, and the future, Cell source
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The implantation theory (1, 11, 201) was a reasonable hypothesis when formulated, while the metaplasia theory (31) was a histologic observation that did not consider genetic or epigenetic changes.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
What the sources say
- Not checked yetcites [1] Sampson, 1927, Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity, Am J Obstet Gynecol source
- Not checked yetcites [11] Sampson, 1924, Benign and malignant endometrial implants in the peritoneal cavity, and their relation to certain ovarian tumors, Surg Gynecol Obstet
- Not checked yetcites [201] Sampson, 1925, Heterotopic or misplaced endometrial tissue, Am J Obstet Gynecol source
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. 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
“A better interpretation of metaplasia is that the underlying mechanisms can be reversible or irreversible changes, and both can be transmitted.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. 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
“If metaplasia is defined as metaplastic changes without permanent and transmissible genetic or epigenetic changes, the resulting endometriosis cells are genetically and epigenetically similar to endometrium and lesions after retrograde menstruation and implantation.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > THE PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY Historical Background
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“As an example, the high glycodelin concentrations in peritoneal fluid might protect early lesions from NK cell attack (261, 262) and could thus facilitate survival.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > GROWTH AND MATURATION OF TYPICAL, CYSTIC, AND DEEP ENDOMETRIOSIS LESIONS
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“It is compatible with hereditary aspects and with a predisposition to develop endometriosis, and it explains why dioxin and total body radiation could increase the risk of endometriosis.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The retrograde menstruation and implantation theory does not explain all clinical observations (Table 1), such as extragenital endometriosis (220), endometriosis in women without endometrium (31) and in men (33), or the clonal aspect (149).”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > THE PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY Historical Background
What the sources say
- Not checked yetcites [220] Davis, 2017, Extrapelvic endometriosis, Semin Reprod Med
- Not checked yetcites [31] Gruenwald, 1942, Origin of endometriosis from the mesenchyme of the celomic walls, Am J Obstet Gynecol source
- Not checked yetcites [33] Jabr, 2014, An unusual cause of abdominal pain in a male patient: endometriosis, Avicenna J Med source
Load-bearingStrength:plain· not yet calibratedTests✓ 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
“The clinical suggestion that typical, cystic, and deep endometriosis are three different diseases seems logical.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
Strength:hedged· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. 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
“It can explain the high prevalence in the peritoneal cavity and the increasing prevalence with increased retrograde menstruation.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
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
“However, new lesions can be formed after new incidents, and the probability that this happens increases with the cumulative genetic and epigenetic abnormalities transmitted at birth and acquired throughout life.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > Koninckx. Pathogenesis of endometriosis. Fertil Steril 2018.
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
“The genetic/epigenetic theory (Fig. 2) is an update of the EDT by adding current knowledge of genetic and epigenetic changes and of the redundancy of cellular processes.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > The Genetic/Epigenetic Theory
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Functional redundancy is a characteristic of many cellular processes.
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
“Las lesiones sutiles se visualizan como endometrio en un entorno diferente hasta que aparecen alteraciones adicionales.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > References
Load-bearingStrength:plain· 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.
In the paper
“Although the mechanisms of reactivation are not understood, deep endometriosis seems to be reactivated by trauma, such as by in vitro fertilization-related needle punctures for oocyte pick-up, triggering the subsequent development of more severe lesions and even a frozen pelvis (56), as frequently observed.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
What the sources say
- Not checked yetcites [56] Canis, 2016, Endometriosis may not be a chronic disease: an alternative theory offering more optimistic prospects for our patients, Fertil Steril source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“These models remain valid to study the effect of abnormal environments on (normal) endometrium.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. 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
“The polygenetic/ polyepigenetic theory is compatible with observations made up to now.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
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
“It is suggested that the same mechanisms apply to adenomyosis.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“Similarly to uterine myomas, endometriosis lesions can remain dormant without progression for longer periods of time.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“The poor definition of metaplasia continues to create confusion.”
§ Pathogenesis of endometriosis: the genetic/epigenetic theory > DISCUSSION
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Many words in the endometriosis literature are not clear.
The paper relies on this without support.
There is no nonhuman animal model with sufficient similarity to the human myometrium, junctional zone, endometrium, placentation, and pregnancy disorders such as preeclampsia.
“There is no nonhuman animal model with sufficient similarity to the human myometrium, junctional zone (JZ), endometrium, placentation, and pregnancy disorders, such as preeclampsia.”
The paper relies on this without support.
Functional redundancy is a characteristic of many cellular processes.
“Second, functional redundancy is a characteristic of many cellular processes.”
The authors state this as an assumption.
The original cell can be an endometrial cell, a stem cell, or a bone marrow cell with inherited genetic and epigenetic defects.
“The original cell can be an endometrial cell, a stem cell, or a bone marrow cell with their inherited genetic and epigenetic defects.”
The paper relies on this without support.
Many words in the endometriosis literature are not clear.
“Many words in the endometriosis literature are not clear.”
The paper relies on this without support.
The meanings of words often change over time, especially after new clinical and molecular-biologic observations are added to the initial clinical, macroscopic, and microscopic descriptions.
“This confusion stems from the fact that the meanings of words often change over time, especially after new clinical and molecular-biologic observations are added to the initial clinical, macroscopic, and microscopic descriptions.”
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
“It is believed that genetic and epigenetic conditions are rather conducive to the development of endometriosis, which is caused by environmental factors, or genetic and epigenetic changes caused by environmental factors are necessary to move from subtle changes in endometriosis to the disease stage [179].”
From Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature) (2021) · cites this paper as [179]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Twin-sister claim cites a study of nontwin sisters
MinorThe paper cites reference 44 for a claim about age of onset in twin sisters, but reference 44 is explicitly about nontwin sisters.
“In twin sisters, the prevalence (40)(41)(42)(43) and the age of onset (44) of endometriosis are similar.”
“44. Kennedy S, Hadfield R, Mardon H, Barlow D. Age of onset of pain symp- toms in nontwin sisters concordant for endometriosis.”
Citations
Cites
Mutation and cancer: statistical study of retinoblastoma
Knudson, A. G. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.4.820 · Cited by 7,612
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Sampson, J. A. (1927) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30003-x · Cited by 2,334
An operational definition of epigenetics: Figure 1.Preprint
Berger, S. L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009) · Genes & Development · doi:10.1101/gad.1787609 · Cited by 1,889
Bulun, S. E. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804690 · Cited by 1,772
(1927) · PubMed Central · Cited by 1,008
(1984) · PubMed · Cited by 997
Koninckx, P. R., Meuleman, C., Demeyere, S., Lesaffre, E., & Cornillie, F. J. (1991) · Fertility and Sterility · doi:10.1016/s0015-0282(16)54244-7 · Cited by 849
Recurrence of endometriosis and its control
Guo, S.-W. (2009) · Human Reproduction Update · doi:10.1093/humupd/dmp007 · Cited by 719
Flagged first, then by citations
23 of the 290 references couldn’t be matched to a known paper.
Research works printed but not linked: 9
- Rokitansky, 1860, Über Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen, Zeitschr Ges Aerzte Wien, 16, 577
- Cullen, 1896, Adeno-myoma of the round ligament, Johns Hopkins Hosp Bull, 7, 112
- Cullen, 1896, Adenoma-myoma uteri diffusum benignum, J Hopkins Hosp Bull, 6, 133
- Cullen, 1919, The distribution of adenomyomata containing uterine mucosa, Am J Obstet Gynecol, 80, 130
- Batt, 2007, Mullerianosis, Histol Histopathol, 22, 1161
- Sampson, 1924, Benign and malignant endometrial implants in the peritoneal cavity, and their relation to certain ovarian tumors, Surg Gynecol Obstet, 38, 287
- Fallon, 1950, Endometriois: a report of 400 cases, R I Med J, 33
- Asencio FA, Ribeiro HA, Ribeiro PA, Mario M, Adamyan L, Ussia A, et al. Case reports and systematic review of estrogen independent symptomatic postmenopausal endometriosis. Gynecol Surgery 2018. In press.
- Meyer, 1923, Zur frage der Urnieren-genese van Adenomyomen, Zentralbl Gynakol, 15, 577
Cited by
Sorted by citations
Smolarz, B., Szyłło, K., & Romanowicz, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910554 · Cited by 560
Pathological angiogenesis: mechanisms and therapeutic strategies
Dudley, A. C., & Griffioen, A. W. (2023) · Angiogenesis · doi:10.1007/s10456-023-09876-7 · Cited by 571
The 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
Self-citationPathogenesis Based Diagnosis and Treatment of Endometriosis
Koninckx, P. R., Fernandes, R., Ussia, A., Schindler, L., Wattiez, A., Al-Suwaidi, S., Amro, B., Al-Maamari, B., Hakim, Z. T., & Tahlak, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.745548 · Cited by 305
Self-citationExtrapelvic Endometriosis: A Systematic Review
Andres, M. P., Arcoverde, F. V. L., Souza, C. C. C., Fernandes, L. F. C., Abrão, M. S., & Kho, R. M. (2020) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2019.10.004 · Cited by 276
Pathogenesis of Endometriosis: The Origin of Pain and Subfertility
Gruber, T. M., & Mechsner, S. (2021) · Cells · doi:10.3390/cells10061381 · Cited by 237
“The high coincidence of these two EM subtypes may arise in one common pathogenesis [1,2], which has been discussed since 1927.”
BackgroundProgesterone Actions and Resistance in Gynecological Disorders
MacLean, J. A., & Hayashi, K. (2022) · Cells · doi:10.3390/cells11040647 · Cited by 199
“Although adenomyosis and endometriosis share several histological and molecular features [140], patients with adenomyosis often suffer menorrhagia and pregnancy loss, including recurrent implantation failures and miscarriages [141,142].”
BackgroundDonnez, J., & Dolmans, M.-M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10051085 · Cited by 182
The emerging role of ferroptosis in female reproductive disorders
Liu, M., Ke-ming, W., & Wu, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115415 · Cited by 156
Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations
Inoue, S., Hirota, Y., Ueno, T., Fukui, Y., Yoshida, E., Hayashi, T., Kojima, S., Takeyama, R., Hashimoto, T., Kiyono, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13708-y · Cited by 143
The epidemiology of endometriosis is poorly known as the pathophysiology and diagnosis are unclear
Koninckx, P. R., Ussia, A., Adamyan, L. V., Tahlak, M., Keckstein, J., Wattiez, A., & Martin, D. C. (2020) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2020.08.005 · Cited by 136
Self-citationThree-dimensional understanding of the morphological complexity of the human uterine endometrium
Yamaguchi, M., Yoshihara, K., Suda, K., Nakaoka, H., Yachida, N., Ueda, H., Sugino, K., Mori, Y., Yamawaki, K., Tamura, R., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102258 · Cited by 123
“…endometrial hyperplasia, and endometrial cancer originate in the uterine endometrium due to its high intrinsic regenerative capacity, and these diseases affect the lives of women from puberty until after menopause (Garcia-Solares et al., 2018; Koninckx et al., 2019; Morice et al., 2016).”
BackgroundEpigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics
Marquardt, R. M., Tran, D. N., Lessey, B. A., Rahman, M. S., & Jeong, J. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad020 · Cited by 137
Filip, L., Duică, F., Prădatu, A., Crețoiu, D., Suciu, N., Creţoiu, S. M., Predescu, D. V., Varlas, V. N., & Voinea, S.-C. (2020) · Medicina · doi:10.3390/medicina56090460 · Cited by 137
Current 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
Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target
Agostinis, C., Balduit, A., Mangogna, A., Zito, G., Romano, F., Ricci, G., Kishore, U., & Bulla, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599117 · Cited by 123
“By analysing global promoter methylation patterns, researchers have demonstrated that differentially methylated genes are associated with immune surveillance, inflammatory response, cell adhesion and negative regulation of apoptosis (21).”
BackgroundEndometriosis: Part I. Basic concept
Wang, P., Yang, S., Chang, W.-H., et al. (2022) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2022.08.002 · Cited by 113
Pre- and postsurgical medical therapy for endometriosis surgery
Chen, I., Veth, V. B., Choudhry, A. J., Murji, A., Zakhari, A., Black, A., Agarpao, C., & Maas, J. W. M. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003678.pub3 · Cited by 121
Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?
Konrad, L., Dietze, R., Riaz, M. A., Scheiner‐Bobis, G., Behnke, J., Horné, F., Hoerscher, A., Reising, C., & Meinhold-Heerlein, I. M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061915 · Cited by 115
Abdominal wall endometriosis (a narrative review)
Carsote, M., Terzea, D. C., Valea, A., & Gheorghisan-Galateanu, A.-A. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.38679 · Cited by 111
Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives
Terzić, M., Aimagambetova, G. N., Kunz, J., Bapayeva, G., Aitbayeva, B., Terzic, S., & Laganà, A. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179274 · Cited by 115
Adolescent Endometriosis: An Update
Shim, J. Y., & Laufer, M. R. (2019) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2019.11.011 · Cited by 109
Ma, J., Zhang, L., Zhan, H., Mo, Y., Ren, Z., Shao, A., & Lin, J. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00637-x · Cited by 106
“Nevertheless, we could identify the regulatory mechanism underlying the altered processes in FB trajectory, which might be related to epigenetic modification [41].”
BackgroundGenetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis
Zubrzycka, A., Zubrzycki, M., Perdas, E., & Zubrzycka, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051309 · Cited by 101
McNamara, H. C., Frawley, H., Donoghue, J. F., Readman, E., Healey, M., Ellett, L., Reddington, C., Hicks, L. J., Harlow, K., Rogers, P. A. W., et al. (2021) · Frontiers in Reproductive Health · doi:10.3389/frph.2021.729642 · Cited by 107
Pathogenesis of endometriosis: Look no further than John Sampson
Yovich, J. L., Rowlands, P. K., Lingham, S., Sillender, M., & Srinivasan, S. (2019) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2019.10.007 · Cited by 95
Giudice, L. C., Oskotsky, T., Falako, S., Opoku‐Anane, J., & Sirota, M. (2023) · The FASEB Journal · doi:10.1096/fj.202300907 · Cited by 110
New Understanding of Diagnosis, Treatment and Prevention of Endometriosis
Amro, B., Aristondo, M. E. R., Al-Suwaidi, S., Al-Maamari, B., Hakim, Z. T., Tahlak, M., Wattiez, A., & Koninckx, P. R. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116725 · Cited by 87
Self-citationNK Cells as Potential Targets for Immunotherapy in Endometriosis
Ścieżyńska, A., Komorowski, M., Soszyńska, M., & Malejczyk, J. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8091468 · Cited by 83
“Endometriosis is a complex disease that depends on a variety of still poorly defined genetic, immune and environmental factors [1,2,9,10].”
BackgroundEndometrial microbiota is more diverse in people with endometriosis than symptomatic controls
Wessels, J. M., Domínguez, M. A., Leyland, N. A., Agarwal, S. K., & Foster, W. G. (2021) · Scientific Reports · doi:10.1038/s41598-021-98380-3 · Cited by 88
Exploring diagnostic m6A regulators in endometriosis
Jiang, L., Zhang, M., Wu, J., Wang, S., Xiang, Y., Yi, M., Zhang, X., & Fang, X. (2020) · Aging · doi:10.18632/aging.202163 · Cited by 83
“alterations might play a critical role in the development of EMs [4], including DNA methylation, histone acetylation, and microRNA dysregulation [5].”
BackgroundMariadas, H., Chen, J.-H., & Chen, K.-H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062458 · Cited by 107
“…mesothelial–mesenchymal transitions and the role of bone marrow cells in peritoneal repair, highlighting that the metaplastic cells involved in endometriosis are genetically and epi-genetically similar to endometrial cells, aligning with theories of retrograde menstruation and implantation [13,14].”
Endometriosis: Classification, pathophysiology, and treatment options
Pašalić, E., Tambuwala, M. M., & Hromić‐Jahjefendić, A. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154847 · Cited by 80
The bidirectional relationship between endometriosis and microbiome
Uzuner, C., Mak, J., El‐Assaad, F., & Condous, G. S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1110824 · Cited by 79
Pathogenesis 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
“[62] hypothesized in a recent review that a common molecular mechanism might be involved in the pathogenesis of these disorders.”
BackgroundEndocrine disruptors and endometriosis
Dutta, S., Banu, S. K., & Arosh, J. A. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.11.007 · Cited by 78
Relationship 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
“Some researchers have shown that genetic alterations may be epigenetically regulated [10,11].”
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
Anderson, G. (2019) · BioMolecular Concepts · doi:10.1515/bmc-2019-0017 · Cited by 67
Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity
Szukiewicz, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.943839 · Cited by 65
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
“The genetic/epigenetic theory adds to this and suggests that the genetic and epigenetic changes and the redundancy of cellular processes promote changes that contribute to the disease [41].”
BackgroundWang, X., Wang, J., Zhao, X., Wu, H., Li, J., Cheng, Y. F., Guo, Q., Cao, X., Liang, T., Sun, L., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04209-0 · Cited by 63
Delanerolle, G., Ramakrishnan, R., Hapangama, D. K., Zeng, Y., Shetty, A., Elneil, S., Chong, S., Hirsch, M., Oyewole, M., Phiri, P., et al. (2021) · Women s Health · doi:10.1177/17455065211019717 · Cited by 61
“An eight item scale with three quality parameters of (1) selection, (2) comparability and (3) outcome.”
BackgroundImmunology and Immunotherapy of Endometriosis
Maksym, R., Hoffmann, M., Skibińska, M., Rabijewski, M., Mackiewicz, A. A., & Kiéda, C. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10245879 · Cited by 61
“responsible for maintaining the disorder and the impairment of reproductive functions [4,5].”
BackgroundCircular RNA in disease: Basic properties and biomedical relevance
Chen, X., Zhou, M., Yant, L. J., & Huang, C. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1723 · Cited by 53
“Endometrial fibrosis, endometriosis-associated infertility, and pre-eclampsia (PE) are some of the most common gynecological diseases worldwide, and the association of circRNAs with those diseases has been revealed (Gao et al., 2021; Koninckx et al., 2019; Yu et al., 2008; Table 3).”
BackgroundAsencio, F. D. A., Ribeiro, H. S. A. A., Ribeiro, P. A., Malzoni, M., Adamyan, L. V., Ussia, A., Gomel, V., Martin, D. C., & Koninckx, P. R. (2019) · Gynecological Surgery · doi:10.1186/s10397-019-1056-x · Cited by 55
Self-citationKoninckx, P. R., Ussia, A., Wattiez, A., Adamyan, L. V., Martin, D. C., & Gordts, S. (2021) · Facts Views and Vision in ObGyn · doi:10.52054/fvvo.13.3.028 · Cited by 52
Self-citationKimber-Trojnar, Ż., Pilszyk, A., Niebrzydowska-Tatus, M., Pilszyk, Z., Ruszała, M., & Leszczyńska‐Gorzelak, B. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10132762 · Cited by 54
Olkowska‐Truchanowicz, J., Białoszewska, A., Zwierzchowska, A., Sztokfisz-Ignasiak, A., Janiuk, I. R., Dabrowski, F. A., Korczak-Kowalska, G., Barcz, E., Bocian, K., & Malejczyk, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158134 · Cited by 52
Moreira, M. D. F., Gamboa, O. L., & Pinho Oliveira, M. A. (2022) · European Journal of Pain · doi:10.1002/ejp.1939 · Cited by 48
“Endometriosis is a heterogeneous gynaecological disease characterized by endometrial glands and stroma outside the uterine cavity, associated with immunologic, genetic, hormonal and environmental factors (Koninckx et al., 2019).”
BackgroundDonnez, J., & Dolmans, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111342 · Cited by 54
“Their progression is slow [2,86,87] and it is difficult at the time of diagnosis to establish exactly when the lesion developed, grew, and ceased its evolution.”
BackgroundRNA N6-methyladenosine modification in female reproductive biology and pathophysiology
Huang, E., & Chen, L. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01078-4 · Cited by 54
Peinado, F. M., Romero, I. L., Sotelo, R., Iribarne-Durán, L. M., Fernández-Parra, J., Vela-Soria, F., Olea, N., Fernández, M. F., Freire, C., León, J., et al. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17041194 · Cited by 46
“Besides genetic susceptibility [7,8], environmental factors have been proposed as crucial orchestrators of endometriosis development [9].”
BackgroundKoninckx, P., Ussia, A., Tahlak, M., Adamyan, L. V., Wattiez, A., Martin, D. C., & Gomel, V. (2019) · PubMed Central · Cited by 52
Self-citationMicrobiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together—A Review
Salmeri, N., Sinagra, E., Dolci, C., Buzzaccarini, G., Sozzi, G., Sutera, M., Candiani, M., Ungaro, F., Massimino, L., Danese, S., et al. (2023) · Microorganisms · doi:10.3390/microorganisms11082089 · Cited by 44
Adenomyosis and Infertility: A Literature Review
Pados, G., Gordts, S., Sorrentino, F., Nisolle, M., Nappi, L., & Daniilidis, A. (2023) · Medicina · doi:10.3390/medicina59091551 · Cited by 56
“[19] have proposed the genetic–epigenetic theory for endometriosis that can be equally applied to adenomyosis, as these two conditions share common patterns of aberrant gene expression [20,21].”
BackgroundThe Estrogen–Immune Interface in Endometriosis
Greygoose, E., Metharom, P., Kula, H., Seckin, T. K., Seckin, T. A., Ayhan, A., & Yu, Y. (2025) · Cells · doi:10.3390/cells14010058 · Cited by 50
“Dysregulated immune responses in the peritoneal environment may fail to eliminate misplaced endometrial cells, allowing them to implant [29,30].”
Possible role of microbiome in the pathogenesis of endometriosis
D’Alterio, M. N., GIULIANI, C., Scicchitano, F., Laganà, A. S., Oltolina, N., Sorrentino, F., Nappi, L., Orrù, G., & Angioni, S. L. (2021) · Minerva Obstetrics and Gynecology · doi:10.23736/s2724-606x.21.04788-2 · Cited by 47
Chiu, C.-C., Hsu, T., Jiang, L.-Y., Chan, I., Shih, Y.-C., Chang, Y., Wang, P., & Chen, Y. (2022) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2021.11.024 · Cited by 45
Tan, J., Yong, P. J., & Bedaiwy, M. A. (2019) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000555 · Cited by 42
“Together, these recent studies suggest that specific subtypes of uterine adenomyosis and deep endometriotic nodules may share a common epigenetic pathogenesis [15,16].”
BackgroundCellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics
Filby, C. E., Rombauts, L. J. F., Montgomery, G. W., Giudice, L. C., & Gargett, C. E. (2020) · Seminars in Reproductive Medicine · doi:10.1055/s-0040-1713429 · Cited by 40
Immunopathogenesis of endometriosis—A novel look at an old problem
Chopyak, V. V., Koval, H. D., Havrylyuk, A. M., Lishchuk-Yakymovych, K. A., Potomkina, H. A., & Kurpisz, M. K. (2022) · Central European Journal of Immunology · doi:10.5114/ceji.2022.113830 · Cited by 41
“However, the exact genetic basis of endometriosis is not yet clear and the exact etiopathogenic mechanism of endometriosis remains to be determined [9, 26].”
BackgroundSzukiewicz, D., Stangret, A., Ruiz‐Ruiz, C., Olivares, E. G., Şoriţău, O., Șușman, S., & Szewczyk, G. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10115-5 · Cited by 42
Wan, Y., Gu, C., Kong, J., Sui, J., Zuo, L., Song, Y., & Chen, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-04963-z · Cited by 40
A Call for New Theories on the Pathogenesis and Pathophysiology of Endometriosis
Canis, M. J., Abbott, J. A., Abrão, M. S., Al‐Jefout, M., Bedaiwy, M. A., Benagiano, G., Burns, K. A., Canis, M. J., Carmona, F., Chapron, C., et al. (2024) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2024.02.004 · Cited by 39
Self-citationEndometriosis: What is the Influence of Immune Cells?
Crispim, P. C. A., Jammal, M. P., Murta, E. F. C., & Nomelini, R. S. (2020) · Immunological Investigations · doi:10.1080/08820139.2020.1764577 · Cited by 40
“It is believed that the intrinsic properties of endometrial tissue ensure the viability and neovascularization of ectopic lesions in women with endometriosis (Koninckx et al. 2019; Taylor et al. 2002).”
BackgroundReid, R., Steel, A., Wardle, J., McIntyre, E., Harnett, J., Foley, H., & Adams, J. (2019) · BMC Research Notes · doi:10.1186/s13104-019-4114-6 · Cited by 38
Challenges in uncovering non-invasive biomarkers of endometriosis
Hudson, Q. J., Perricos, A., Wenzl, R. J., & Yotova, I. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220903270 · Cited by 41
Vercellini, P., Salmeri, N., Somigliana, E., Piccini, M., Caprara, F., Viganò, P., & Matteis, S. D. (2024) · Human Reproduction · doi:10.1093/humrep/deae086 · Cited by 41
“…spectrum of factors, including genetic and epigenetic modifications, and immunological and hormonal influences, as well as lifestyle and environmental exposures, all of which can contribute to the complex, multisystemic phenotype of endometriosis (Koninckx et al. , 2019; Zondervan et al. , 2020).”
Reproductive technologies, female infertility, and the risk of imprinting-related disorders
Fauque, P., de Mouzon, J., Devaux, A., Epelboin, S., Boyer, M. G., Lévy, R., Valentin, M., Viot, G., Bergère, A., de Vienne, C. M., et al. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00986-3 · Cited by 38
“Interestingly, there is increasing evidence that some female infertility syndromes such as polycystic ovary syndrome (PCOS) [16] or endometriosis [17] are associated with epigenetic alterations.”
BackgroundArchimetrosis: the evolution of a disease and its extant presentation
LEYENDECKER, G., Wildt, L., Laschke, M. W., & Mall, G. (2022) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-022-06597-y · Cited by 38
“According to a proposed definition, deeply infiltrating archimetrosis (endometriosis) is present when the depth of infiltration of the foci exceeds 5 mm [65, 210].”
BackgroundEndometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells
Olkowska‐Truchanowicz, J., Sztokfisz-Ignasiak, A., Zwierzchowska, A., Janiuk, I. R., Dabrowski, F. A., Korczak-Kowalska, G., Barcz, E., Bocian, K., & Malejczyk, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173789 · Cited by 37
Emerging Drug Targets for Endometriosis
Dolmans, M., & Donnez, J. (2022) · Biomolecules · doi:10.3390/biom12111654 · Cited by 40
“A genetic basis and epigenetic influence [21,22] along with neonatal progesterone resistance may of course affect the degree of progesterone resistance, as discussed in several reviews [11,16,23–26].”
BackgroundSzukiewicz, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512195 · Cited by 39
Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature
Михалева, Л. М., Radzinsky, V. E., Orazov, M. R., Николаевна, Х. Т., Sorokina, A. V., Александрович, М. С., Владимировна, В. С., Shustova, V. B., & Sinelnikov, M. Y. (2021) · International Journal of Women s Health · doi:10.2147/ijwh.s306135 · Cited by 37
Endometriosis and inflammatory immune responses: Indian experience
Gajbhiye, R. (2022) · American Journal of Reproductive Immunology · doi:10.1111/aji.13590 · Cited by 37
Organoids of the Female Reproductive Tract: Innovative Tools to Study Desired to Unwelcome Processes
Heremans, R., Jan, Ž., Timmerman, D., & Vankelecom, H. E. J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.661472 · Cited by 36
Environmental Factors and Endometriosis
Polak, G., Banaszewska, B., Filip, M., Radwan, M., & Wdowiak, A. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182111025 · Cited by 34
“The risk of endometriosis is 6–9% higher in first-degree relatives of women with endometriosis and 15% higher when they had severe disease [59].”
BackgroundKoninckx, P. R., Ussia, A., Tahlak, M., Adamyan, L., Wattiez, A., Martin, D. C., & Gomel, V. (2019) · Lirias · Cited by 34
Self-citationHow is small bowel permeability in endometriosis patients? a case control pilot study
Viganò, D., Zara, F., Pinto, S. W. L., Loddo, E., Casula, L., Soru, M. B., D’Ancona, G., D’Alterio, M. N., GIULIANI, C., Angioni, S. L., et al. (2020) · Gynecological Endocrinology · doi:10.1080/09513590.2020.1766440 · Cited by 33
BIRC5/Survivin Expression as a Non-Invasive Biomarker of Endometriosis
Filipchiuk, C., Laganà, A. S., Beteli, R., Ponce, T. G., Christofolini, D. M., Trevisan, C. M., Fonseca, F. L. A., Barbosa, C. P., & Bianco, B. A. V. (2020) · Diagnostics · doi:10.3390/diagnostics10080533 · Cited by 33
“All these findings corroborate different theories for the origin of endometriosis, such as the theory of endometrial stem cells [52] or the increase in transient progenitor cells in which circulating stem cells originating from bone marrow or the basal layer of the endometrium can differentiate into endometrial tissue…”
BackgroundIs chronic endometritis associated with tubal infertility? A prospective cohort study.
Holzer, I., Ott, J., Kurz, C., Hofstetter, G., Hager, M., Kuessel, L., & Parry, J. (2021) · Journal of minimally invasive gynecology · doi:10.1016/j.jmig.2021.04.011 · Cited by 32
Gene Expression Signature of Endometrial Samples from Women with and without Endometriosis
Adamyan, L. V., Aznaurova, Y. B., Stepanian, A. A., Nikitin, D. M., Garazha, A., Suntsova, M., Sorokin, M., & Buzdin, A. A. (2021) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2021.03.011 · Cited by 34
Self-citationDioxin and endometriosis: a new possible relation based on epigenetic theory
Giampaolino, P., Corte, L. D., Foreste, V., Barra, F., Ferrero, S., & Bifulco, G. (2019) · Gynecological Endocrinology · doi:10.1080/09513590.2019.1698024 · Cited by 32
Pathogenesis of bowel endometriosis
Yong, P. J., Bedaiwy, M. A., Alotaibi, F. T., & Anglesio, M. S. (2020) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2020.05.009 · Cited by 35
Ota, I., Taniguchi, F., Ota, Y., Nagata, H., Wada, I., Nakaso, T., Ikebuchi, A., Sato, E., Azuma, Y., & Harada, T. (2021) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12408 · Cited by 34
Endometriosis is associated with pregnancy loss: a nationwide historical cohort study
Boje, A. D., Egerup, P., Westergaard, D., Bertelsen, M.-L. M. F., Nyegaard, M., Hartwell, D., Lidegaard, Ø., & Nielsen, H. S. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2022.12.042 · Cited by 31
Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health
Kapper, C., Oppelt, P., Ganhör, C., Gyunesh, A. A., Arbeithuber, B., Stelzl, P., & Rezk, M. (2024) · Nutrients · doi:10.3390/nu16071008 · Cited by 51
“Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity [243,244] leading to a microenvironment established by endometriotic lesions, which is dominated by inflammation and oxidative processes [245].”
BackgroundDonnez, O. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10215183 · Cited by 29
Méar, L., Com, E., Fathallah, K., Laetitia Guillot, D., Lavigne, R., Guével, B., Fauconnier, A., Vialard, F., & Pineau, C. (2022) · Diagnostics · doi:10.3390/diagnostics12020419 · Cited by 30
“This would be possible through retrograde menstruation, and the theory is supported by several epidemiological and anatomical facts [10,11].”
Role for autophagy-related markers Beclin-1 and LC3 in endometriosis
Kong, Z., & Yao, T. (2022) · BMC Women s Health · doi:10.1186/s12905-022-01850-7 · Cited by 32
“These cells require additional genetic or epigenetic changes to alter behavior and develop typical, cystic, deep, or other lesions [9].”
BackgroundPeritoneal fluid progesterone and progesterone resistance in superficial endometriosis lesions
Koninckx, P. R., Ussia, A., Adamyan, L. V., Gomel, V., & Martin, D. C. (2021) · Human Reproduction · doi:10.1093/humrep/deab258 · Cited by 28
Self-citationPeng, H., Weng, L., Lei, S., Hou, S., Yang, S., Li, M., & Zhao, D. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00793-1 · Cited by 29
Research advances in drug therapy of endometriosis
Shi, J., Tan, X., Feng, G., Yuan, Z., Jiang, Z., Banda, S., Wang, L., Zheng, W., Chen, L., Yu, D., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1199010 · Cited by 30
“Studies of endometriosis mesenchymal cells provided clues to epigenomic alterations leading to heritable traits without altering DNA sequences (Peiris et al., 2018; Koninckx et al., 2019).”
BackgroundThe Importance of Stromal Endometriosis in Thoracic Endometriosis
Mecha, E. O., Makunja, R., Maoga, J. B., Mwaura, A. N., Riaz, M. A., Omwandho, C. O. A., Meinhold-Heerlein, I. M., & Konrad, L. (2021) · Cells · doi:10.3390/cells10010180 · Cited by 29
“of additional causative factors like inflammation, oxidative stress [11], disturbance of the peritoneal barrier [12], and genetic/epigenetic changes [5], which then affect migration, adhesion, and invasion of endometrial cells at ectopic sites.”
BackgroundMasciullo, L., Viscardi, M. F., Piacenti, I., Scaramuzzino, S., CAVALLI, A., Piccioni, M. G., & Porpora, M. G. (2021) · Minerva Obstetrics and Gynecology · doi:10.23736/s2724-606x.21.04779-1 · Cited by 25
Kim, H. G., Lim, Y. S., Hwang, S.-Y., Kim, H.-Y., Moon, Y., Song, Y. J., Na, Y.-J., & Yoon, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073938 · Cited by 27
“In addition to the classic implantation hypothesis, alternative hypotheses such as metaplasia [12], inflammatory and immunologic responses [11], peritoneal barrier disturbance [13], genetic and epigenetic changes [14], circulating stem/progenitor cells [15], and repeated tissue injury and repair [16] have also been su…”
BackgroundCesarean Section: A Potential and Forgotten Risk for Abdominal Wall Endometriosis
Ananias, P., Luenam, K., Melo, J. P., Jose, A. M., Yaqub, S., Turkistani, A., Shah, A., & Mohammed, L. (2021) · Cureus · doi:10.7759/cureus.17410 · Cited by 26
“Moreover, non-surgical endometriosis is considered hereditary, and patients with first degree relatives have a risk of 6-9% higher of developing the disease [23], possibly due to genetic and epigenetic changes in endometrial cells, which may also be involved in AWE; however, more studies are necessary [2].”
BackgroundMetabolomic biomarkers of endometriosis: A systematic review
Adamyan, L. V., Pivazyan, L. G., Zarova, E., Avetisyan, J. S., Laevskaya, A., Sarkisova, A., & Stepanian, A. A. (2024) · Journal of Endometriosis and Uterine Disorders · doi:10.1016/j.jeud.2024.100077 · Cited by 27
Self-citationAdvances in the diagnosis and management of endometriosis: A comprehensive review
Chen, Y., Waseem, S., & Luo, L. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.155813 · Cited by 33
Metadata
- Authors
- Koninckx, P. R., Ussia, A., Adamyan, L., Wattiez, A., Gomel, V., & Martin, D. C.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Russian University of Medicine (RU)
- Latifa Hospital (AE)
- University of British Columbia (CA)
- University of Tennessee Health Science Center (US)
- Corresponding author
- Koninckx, Philippe R.
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 111
- Issue
- 2
- Pages
- 327-340
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2903882793
- Semantic Scholar
- bda1b43240a49c67f04356783de4dff519d10820
- Cited by
- 427
- References
- 290
- Citations by year
- 2026: 35 · 2025: 60 · 2024: 52 · 2023: 80 · 2022: 61 · 2021: 76 · 2020: 44 · 2019: 19
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- 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 pathogenesis, genetic theory, epigenetic theory, retrograde menstruation, metaplasia, cystic ovarian lesions, deep infiltrating endometriosis, infertility, adenomyosis, peritonitis, placentation, stem cells
- MeSH terms
- Animals, Endometriosis, Endometrium, Female, Genetic Markers, Humans, Phenotype, Prognosis, Risk Factors, Genetic Predisposition to Disease, Heredity, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
