Abstract:
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.
摘要:
子宫肌瘤是女性最常见的良性肿瘤,以异常子宫出血(AUB)为主要症状。此外,已经建立了子宫肌瘤和不孕症之间的联系,特别是如果子宫肌瘤在子宫腔中突出。激素治疗与副作用以及子宫切除术有关,这与受孕的欲望是不相容的。为了改善治疗,了解与肌瘤相关症状的病因至关重要。我们的目的是评估子宫内膜血管生成在女性子宫肌瘤,有和没有AUB,以及药物治疗对这些患者的影响。此外,我们探讨了血管生成改变在子宫肌瘤和不孕症患者中的可能作用。我们根据PRISMA指南(PROSPERO:CRD42020169061)进行了系统评价,包括15项符合条件的研究。子宫内膜血管内皮生长因子(VEGF)和肾上腺髓质素的表达在子宫肌瘤患者中增加。这表明血管生成异常,可能涉及受干扰的血管成熟,导致不成熟和脆弱的血管。用促性腺激素释放激素激动剂治疗,醋酸乌利司他,连续口服避孕药降低了几个血管生成参数,包括VEGF。如果对患有肌瘤的不育和肥沃患者进行比较,发现骨形态发生蛋白/Smad蛋白途径的表达显着降低,可能是由转化生长因子β的表达增加引起的。为了未来的治疗发展,这些不同的血管生成途径可能是治疗纤维瘤相关症状的目标.