铁在子宫内膜异位症的病理生理中扮演着什么角色？铁过量在发现子宫内膜异位组织的部位表现出来，并与氧化应激、炎症微环境和细胞损伤有关；铁介导的氧化应激与不育、症状的严重程度以及恶性转化独立相关。在子宫内膜异位组织中过量的铁得到证实，并且已经研究和提出了多种机制来解释这一现象。可以肯定的是，铁过量在促进氧化应激和细胞损伤方面发挥着重要作用。虽然证据基础庞大，但目前没有综述来总结我们的理解并突出概括的主题，以加深我们的理解并提出进一步研究方向的建议。 本系统综述与主题分析，检索了PubMed、Embase、Web of Science和Cochrane Library数据库的研究，并在2022年8月以前进行了检索。包括了英语语言的人类和动物研究，通过使用爆炸式MeSH术语（“铁”和“子宫内膜异位症”）和自由文本搜索术语（“铁”、“亚铁”、“铁”、“子宫内膜异位症”、“子宫内膜子宫腺瘤”）进行了识别。 按照PRISMA准则报告了本综述。包括了所有报告关于铁或铁络合物在子宫内膜异位症发病机制中的作用的原始数据的研究。那些没有报告原始数据或提供领域综述的研究被排除。使用Newcastle-Ottawa评分系统对每个纳入的研究进行了偏倚分析。 共鉴定到776篇文章，经过筛选，符合纳入标准的研究有53篇，其中包括6篇动物研究和47篇人类研究，涉及3556名参与者。铁过量在各种组织和液体中得到证实，包括卵巢内膜子宫腺瘤、卵泡、异位子宫内膜病变和腹腔液。氧化应激标志物与高铁水平密切相关，并已证明铁运输蛋白的异常表达。可能存在对铁死亡的异常抗性。铁介导的氧化应激导致炎症微环境，与不育、症状的严重程度以及可能的恶性转化相关。 少数纳入的研究的质量客观较低，存在较高的偏倚风险，可能导致错误结论。此外，多个研究未能适当地通过已知混杂变量（如月经周期相）对纳入的患者进行特征描述，可能使结果引入偏差。 当前文献描绘了异常铁机制和随后的氧化应激在子宫内膜异位症中的中心作用。很可能铁过量至少在一定程度上促进异位子宫内膜病变的持续和增殖。因此，铁机制是新疗法的有吸引力的靶点，包括铁螯合剂或铁-氧化应激途径的效应物。我们对目前的理解存在重要的空白，本综述突出并建议了几个进一步研究的主题。这些包括铁螯合剂的作用、对铁死亡的抗性、铁过量与局部缺氧之间的关系、子宫内膜异位症中的全身铁病理生理以及氧化应激在恶性转化中的作用。 J.W.和S.G.P.受利物浦大学医院NHS基金会信托基金持续临床研究奖学金的支持。本项工作的完成未提出或需要额外的资金要求。C.J.H.受Wellbeing of Women项目经费（RG2137）支持。D.K.H.受Wellbeing of Women项目经费（RG2137）和英国医学研究委员会临床研究培训奖学金（MR/V007238/1）支持。作者声明没有利益冲突。 本研究的方案于2021年8月在PROSPERO数据库中登记（CRD42021272818）。 ©2023作者。由牛津大学出版社代表欧洲人类生殖和胚胎学学会出版。

What is the role of iron in the pathophysiology of endometriosis?Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory micro-environment, and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity, and malignant transformation.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 summarize our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field.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').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 that 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.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 3556 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.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 characterize the included patients by known confounding variables, such as menstrual cycle phase, which may introduce bias to 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 localized hypoxia, systemic iron pathophysiology in endometriosis, and the role of oxidative stress in malignant transformation.J.W. and S.G.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 an MRC clinical research training fellowship (MR/V007238/1). The authors have no conflicts of interest to declare.A protocol was prospectively registered with the PROSPERO database in August 2021 (CRD42021272818).© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.