Macrophages in endometriosis: key roles and emerging therapeutic opportunities-a narrative review

Endometriosis is a chronic gynecological disorder affecting approximately 10% of women of reproductive age. It commonly presents with pelvic pain, dysmenorrhea, and infertility, imposing substantial physical, psychological, and social burdens. Current therapeutic options, such as surgical intervention and hormonal suppression, are constrained by adverse effects and high recurrence rates. Growing evidence implicates immune dysregulation, particularly of macrophages, in the pathophysiology of endometriosis.

This narrative review synthesizes foundational and clinical research on macrophages in endometriosis and integrates emerging evidence from single-cell RNA sequencing and spatial transcriptomics to refine current models of macrophage heterogeneity, ontogeny, and therapeutic opportunities. In endometriosis, macrophages adopt heterogeneous, context-dependent states rather than a simple binary pattern. Lesions contain macrophage populations that, through cytokines, chemokines, and growth factors, are implicated in chronic inflammation, impaired clearance of cellular debris, angiogenesis, neuroimmune interactions, extracellular-matrix remodeling, and fibrosis. These immune-mediated mechanisms support lesion survival and are thought to exacerbate symptoms. Recent studies have highlighted several therapeutic strategies aimed at modulating macrophage behavior, including the inhibition of their recruitment to ectopic sites, reprogramming of their functional phenotypes from pro-inflammatory to pro-resolving states, and targeting macrophage-related signaling pathways and immune checkpoints. These approaches are currently under preclinical and clinical investigation and hold promise for reducing disease recurrence and minimizing systemic side effects.

Macrophages are emerging as central players in the initiation and progression of endometriosis through their contributions to inflammation, lesion maintenance, and fibrogenesis. Targeting macrophage-mediated pathways offers a novel and potentially effective direction for immunomodulatory therapies. A deeper understanding of macrophage plasticity and function within the endometriotic milieu may pave the way for the development of more precise and durable treatment strategies to improve clinical outcomes.