Cited by 249Endometriosis Research and TreatmentGynecological conditions and treatmentsUterine Myomas and Treatments

Structural and molecular features of the endomyometrium in endometriosis and adenomyosis

Benagiano, Giuseppe, Brosens, Ivo, Habiba, Marwan·2014·Human Reproduction Update

Abstract

BACKGROUND Adenomyosis and endometriosis were initially described as 'adenomyoma'. When the retrograde menstruation theory became widely accepted to explain the pathogenesis of endometriosis, since it does not explain adenomyosis, the two conditions came to be seen as distinct entities. However, emerging evidence suggests that both diseases may be linked to changes in the inner portion of the myometrium. In addition, similar anomalies were found in the eutopic endometrium of the two conditions and the debate has re-opened. A common origin for both adenomyosis and endometriosis would have relevance not only for understanding uterine function and pathophysiology, but also for clinical management and treatment. METHODS The Scopus and Medline databases were searched for all original articles published in English up to the end of 2012. Search terms included 'adenomyosis'; 'endometriosis'; 'endometrium'; 'eutopic endometrium'; 'inner myometrium'; 'junctional zone'. Special attention was paid to articles comparing features of eutopic endometrium in the two conditions. RESULTS A number of similarities exist between adenomyosis and endometriosis and, by using magnetic resonance and laparoscopy, it was found that, at least in some subgroups, the two conditions often coexist. In both situations the inner myometrium (or junctional zone) is altered, although alterations are much more marked in adenomyosis where a thickness >12 mm is today considered sufficient for diagnosis. Research has shown differences between the eutopic endometrium of women with both diseases when compared with controls. There is an immune dysfunction and there are alterations of adhesion molecules, cell proliferation and apoptosis. An increase in cytokines and inflammatory mediators has also been observed. Finally, the presence of oxidative stress and anomalies in free-radical metabolism may alter uterine receptivity. When the two conditions were compared, dissimilarities were also observed in the extent of apoptosis inhibition and in the expression of some inflammatory mediators. It is not clear if observed differences are primarily related to presenting symptoms. Finally, both conditions are steroid dependent and research suggests a role for epigenetic mechanisms. The analysis indicates that much of the published research may have been influenced by the method of diagnosis and/or has not been controlled for the presenting symptoms, the concomitant presence of both diseases or full consideration of fluctuations within cycle phase. CONCLUSIONS It is difficult to draw firm conclusions from existing evidence since major diagnostic limitations still exist and there is a systematic bias in clinical presentation. In addition, scanty information is available on the natural history of endometriosis and no studies exist on the natural history of adenomyosis. Notwithstanding these limitations, a number of similarities, but also some differences have been found between the eutopic endometrium in the two diseases. These findings need to be taken with considerable caution as the few instances where the research was repeated yielded conflicting results.

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Crossref · 10.1093/humupd/dmt052

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  • In endometriosis, the uterus has altered endometrial receptivity mainly due to local growth factors changes (integrin, LIF, activin, CRH), hormonal aberrations (ER and PR), and dysperistalsis of myometrium due to adenomyosis.

    “in endometriosis uterus itself has an altered endometrial receptivity mainly due to local growth factors changes (integrin, LIF, activin, CRH), to hormonal aberrations (ER and PR) [9] and to dysperistalsis of myometrium, due to the association to adenomyosis [156, 157].”

    From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [9]

    The JZ myometrium section reports altered uterine contractions in endometriosis and describes abnormal peristalsis as a proposed common mechanism for endometriosis and adenomyosis. The Discussion also discusses perturbed peristalsis and lower receptivity in adenomyosis, but treats the fertility implications as uncertain. The paper does not establish that adenomyosis causes dysperistalsis or reduced endometrial receptivity in women with endometriosis; the growth-factor and hormone claims are attached to a different citation in the printed sentence. (LLM, conf=0.84)

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4 of the 168 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Benagiano G, Brosens I. The history of endometriosis: identifying the disease. Hum Reprod 1991;6:963-968.
  2. Khorram O, Lessey BA. Alterations in expression of endometrial endothelial nitric oxide. Fertil Steril 2002;78:860 -864.
  3. Mehasseb MK, Bell SC, Habiba M. Tamoxifen causes myometrial disruption but not adenomyosis in the C57/BL6J mouse. Reproduction 2010;139:1067 -1075.

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Authors
Benagiano, G., Brosens, I., & Habiba, M.
Affiliations
  • Sapienza University of Rome (IT)
  • Leuven Institute for Fertility and Embryology (BE)
  • University of Leicester (GB)
Corresponding author
Brosens, Ivo
Venue
Human Reproduction Update
Published
2013-10-18
Volume
20
Issue
3
Pages
386-402
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
OpenAlex
W2124690628
Cited by
246
References
168
Citations by year
2026: 15 · 2025: 11 · 2024: 20 · 2023: 20 · 2022: 24 · 2021: 29 · 2020: 26 · 2019: 17 · 2018: 18 · 2017: 19 · 2016: 21 · 2015: 17 · 2014: 8 · 2012: 1
FWCI
2.49
Type
journal article
Language
en
Open access
closed
Locations
  • Human Reproduction Update (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
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 › Uterine Myomas and Treatments
Keywords
endometriosis, adenomyosis, eutopic endometrium, junctional zone, retrograde menstruation, immune dysfunction, adhesion molecules, apoptosis, cytokines, oxidative stress, endometrial receptivity, steroid dependence, epigenetic mechanisms, pathogenesis, diagnostic limitations
MeSH terms
Endometriosis, Endometrium, Female, Humans, Myometrium, Cytokines, Apoptosis, Oxidative Stress, Inflammation Mediators, Adenomyosis

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