Validation of magnetic resonance relaxometry R2 value and cyst fluid iron level for diagnosis of ovarian endometrioma

Imanaka, Shogo; Yamada, Yoshiaki; Kawahara, Naoki; Kobayashi, Hiroshi

doi:10.1080/13510002.2021.1937456

Cited by 2 publications

(3 citation statements)

References 19 publications

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“…The accuracy of this categorization, however, remains to be verified, since the appearance may be a mere reflection of hormone responsiveness or aberrant angiogenesis of the lesions. Two studies investigating specific iron-sensitive MRI techniques as a diagnostic tool for endometriomas ( Takahashi et al, 1996 ; Imanaka et al , 2021b ) also confirmed higher iron levels in endometriomas via cyst fluid sampling.…”

Section: Resultsmentioning

confidence: 82%

“…The iron content of ovarian endometriomas is well studied, with 11 papers reporting on the iron concentrations in this tissue ( Takahashi et al , 1996 ; Iizuka et al , 1998 ; Yamaguchi et al , 2008 ; Singh et al , 2013 ; Sanchez et al , 2014 ; Benaglia et al , 2015 ; Guo et al , 2015 ; Yoshimoto et al , 2015 ; Nagayasu et al , 2020 ; Imanaka et al , 2021a , b ). The findings of Benaglia et al (2015) , Sanchez et al (2014) , Nagayasu et al (2020) , and Singh et al (2013) are summarized elsewhere in this review.…”

Section: Resultsmentioning

confidence: 99%

“…While some studies have compared iron levels in endometriomas to other benign ovarian cysts, others have compared them with malignant ovarian lesions. Endometriomas had significantly higher levels of total, haem, and free iron when compared with serous/mucinous adenomas and mature teratomas ( Iizuka et al , 1998 , Imanaka et al ., 2021b ). They also have higher iron levels (total, haem, and free) compared with clear cell ovarian cancers, and serous/mucinous adenomas ( Yamaguchi et al , 2008 ) and with a pooled group of endometriosis-associated ovarian cancers (EAOCs) ( Yoshimoto et al , 2015 ).…”

Section: Resultsmentioning

confidence: 99%

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The role of iron in the pathogenesis of endometriosis: a systematic review

Wyatt

Fernando

Powell

et al. 2023

Human Reproduction Open

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STUDY QUESTION What is the role of iron in the pathophysiology of endometriosis? SUMMARY ANSWER Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory microenvironment and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity and malignant transformation. WHAT IS KNOWN ALREADY Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage. The evidence base is large, but no comprehensive reviews exist to summarise our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field. STUDY DESIGN, SIZE, DURATION This systematic review with a thematic analysis retrieved studies from the PubMed, Embase, Web of Science and Cochrane Library databases and searches were conducted from inception through to August 2022. Human and animal studies published in the English language were included and identified using a combination of exploded MeSH terms (‘Iron’ and ‘Endometriosis’) and free-text search terms (‘Iron’, ‘Ferric’, ‘Ferrous’, ‘Endometriosis’, ‘Endometrioma’). PARTICIPANTS/MATERIALS, SETTING, METHODS This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning the role of iron or iron complexes in the pathophysiology of endometriosis were included. Studies which did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included study by using the Newcastle-Ottawa scoring system. MAIN RESULTS AND THE ROLE OF CHANCE There were 776 records identified and these were screened down to 53 studies which met the eligibility criteria, including 6 animal and 47 human studies, with 3,556 individual participants. Iron excess is demonstrated in various tissues and fluids, including ovarian endometriomas, ovarian follicles, ectopic endometriotic lesions and peritoneal fluid. Markers of oxidative stress are strongly associated with high iron levels, and aberrant expression of iron-transport proteins has been demonstrated. Abnormal resistance to ferroptosis is likely. Iron-mediated oxidative stress is responsible for a pro-inflammatory micro-environment and is linked to subfertility, symptom severity and, possibly, malignant transformation. LIMITATIONS, REASONS FOR CAUTION A minority of the included studies were of objectively low quality with a high-risk of bias and may lead to misleading conclusions. Additionally, multiple studies failed to appropriately characterise the included patients by known confounding variables such as menstrual cycle phase, which may introduce bias to the findings. WIDER IMPLICATIONS OF THE FINDINGS Current literature depicts a central role of aberrant iron mechanics and subsequent oxidative stress in endometriosis. It is likely that iron excess is at least partly responsible for the persistence and proliferation of ectopic endometriotic lesions. As such, iron mechanics represent an attractive target for novel therapeutics, including iron chelators or effectors of the iron-oxidative stress pathway. There are significant gaps in our current understanding, and this review highlights and recommends several topics for further research. These include the role of iron chelation, resistance to ferroptosis, the relationship between iron excess and localised hypoxia, systemic iron pathophysiology in endometriosis, and the role of oxidative stress in malignant transformation. STUDY FUNDING/COMPETING INTEREST(S) J.W and S.P are supported by clinical fellowships at Liverpool University Hospital NHS Foundation trust. No additional funding was requested or required for the completion of this work. C.J.H. is supported by a Wellbeing of Women project grant (RG2137). D.K.H. is supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). The authors have no conflicts of interest to declare. REGISTRATION NUMBER A protocol was prospectively registered with the PROSPERO database in August 2021 (CRD42021272818)

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Section: Resultsmentioning

confidence: 82%