Abnormal uterine bleeding（AUB）对生活质量的影响显著，具有重要的社会经济影响。治疗选择经常基于试错，不能针对疾病的发病机制。了解疾病的病理生理学是开发新的治疗选择的必要条件。如果没有发现AUB的潜在病因（例如肌瘤，腺肌症，息肉），则子宫内膜相关AUB（AUB-E）通常由原发性子宫内膜障碍引起。当AUB是由已开具的（外源性）荷尔蒙引起时，被归类为医源性AUB（AUB-I）。考虑到血管调节和功能，AUB-E和AUB-I都可能由子宫内膜中血管新生和血管成熟过程中的改变引起异常血管化。我们旨在调查血管新生和成熟在患有AUB的患者中的基本作用，并假设异常子宫内膜血管新生通过不同的机制对AUB-E和AUB-I的发病有重要作用。我们在Cochrane Library、Embase、PubMed和Web of Science等数据库中进行了系统文献查找，检索术语包括血管生成和异常子宫出血，查找截至2021年9月的文献。包括的研究报告了AUB-E或AUB-I的前绝经期妇女子宫内膜的血管生成。排除了病例报告、信函、评论、社论文章和分类为肌层性、肿瘤性或感染性原因的AUB的研究。采用Cochrane工具和Newcastle-Ottawa量表进行风险偏倚评估。共包括2158篇文章中的35篇。患有AUB-E的患者中，血管内皮生长因子A及其受体（1和2），以及血管生成素-1：血管生成素-2比率和Tie-1显著增加。几项研究报告患有AUB-E患者中其他促血管生成和抗血管生成因子的差异表达，表明异常血管成熟和血管的不完整性。总体而言，AUB-E和对照组中的子宫内膜微血管密度（MVD）相当。有趣的是，与对照组相比，AUB-I患者表现出更高的MVD和更高的促血管生成因子表达，特别是在短期荷尔蒙暴露后。这种效应会逐渐消失，在长期暴露后观察到对血管成熟的改变。AUB-E和AUB-I很可能与异常子宫内膜血管新生和血管成熟有关。本文综述支持现有证据表明增加的促血管生成因子和减少的抗血管生成因子引起的血管成熟不良，导致更脆弱和易渗透的血管。这与我们的假设相符，这些机制似乎在AUB-E和AUB-I的病理生理学中起着重要作用。探索这些患者血管生成中的变化可能提供AUB的治疗靶点。©作者（们）2023年。欧洲人类生殖和胚胎学会已经代表牛津大学出版社出版。

Abnormal uterine bleeding (AUB) has a significant socioeconomic impact since it considerably impacts quality of life. Therapeutic options are frequently based on trial and error and do not target disease aetiology. Pathophysiological insight in this disease is required for the development of novel treatment options. If no underlying cause is found for the AUB (e.g. fibroids, adenomyosis, polyps), endometrial-AUB (AUB-E) is usually caused by a primary endometrium disorder. When AUB is induced by prescribed (exogenous) hormones, it is classified as iatrogenic-AUB (AUB-I). Considering vascular modulation and function, AUB-E and AUB-I both could potentially result from abnormal vascularization in the endometrium due to alterations in the process of angiogenesis and vascular maturation.We aim to investigate the fundamental role of angiogenesis and vascular maturation in patients with AUB and hypothesize that aberrant endometrial angiogenesis has an important role in the aetiology of both AUB-E and AUB-I, possibly through different mechanisms.A systematic literature search was performed until September 2021 in the Cochrane Library Databases, Embase, PubMed, and Web of Science, with search terms such as angiogenesis and abnormal uterine bleeding. Included studies reported on angiogenesis in the endometrium of premenopausal women with AUB-E or AUB-I. Case reports, letters, reviews, editorial articles, and studies on AUB with causes classified by the International Federation of Gynecology and Obstetrics as myometrial, oncological, or infectious, were excluded. Study quality was assessed by risk of bias, using the Cochrane tool and the Newcastle-Ottawa Scale.Thirty-five out of 2158 articles were included. In patients with AUB-E, vascular endothelial growth factor A and its receptors (1 and 2), as well as the angiopoietin-1:angiopoietin-2 ratio and Tie-1, were significantly increased. Several studies reported on the differential expression of other pro- and antiangiogenic factors in patients with AUB-E, suggesting aberrant vascular maturation and impaired vessel integrity. Overall, endometrial microvessel density (MVD) was comparable in patients with AUB-E and controls. Interestingly, patients with AUB-I showed a higher MVD and higher expression of proangiogenic factors when compared to controls, in particular after short-term hormone exposure. This effect was gradually lost after longer-term exposure, while alterations in vessel maturation were observed after both short- and long-term exposures.AUB-E and AUB-I are most likely associated with aberrant endometrial angiogenesis and impaired vessel maturation. This review supports existing evidence that increased proangiogenic and decreased antiangiogenic factors cause impaired vessel maturation, resulting in more fragile and permeable vessels. This matches our hypothesis and these mechanisms appear to play an important role in the pathophysiology of AUB-E and AUB-I. Exploring the alterations in angiogenesis in these patients could provide treatment targets for AUB.© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.