Hormonal Dysregulation and Neuroinflammation in Endometriosis: Convergent Druggable Pathways

Endometriosis is a chronic, estrogen-dependent disorder defined by ectopic endometrial-like tissue growth, persistent inflammation, and aberrant innervation. Emerging evidence indicates that disease progression and symptom severity are driven by a reciprocal interaction between hormonal dysregulation and neuroinflammatory signaling. This narrative review synthesizes human-based mechanistic and clinical evidence on the hormonal–neuroinflammatory interface in endometriosis, drawing on peer-reviewed publications retrieved from PubMed and Scopus through November 2025. The publications comprised studies using data from patient-derived tissues, primary endometriotic cells, and clinical cohorts. Several convergent molecular nodes at this interface were identified: the prostaglandin E2–prostaglandin E receptor 2/prostaglandin E receptor 4–aromatase axis, estrogen receptor beta—nuclear factor kappa B signaling, interleukin-6/signal transducer and activator of transcription 3-mediated fibrosis, neurotrophin pathways, transient receptor potential channels (TRPV1/TRPA1), and neurokinin 1 receptor signaling. In this integrated model, endocrine dysfunction fuels neuroinflammation, which in turn impairs steroid responsiveness. This cycle explains the frequent pain–lesion mismatch and the persistence of symptoms despite standard hormonal suppression. Targeting these druggable interface pathways enables better patient stratification and more effective combination therapies for endometriosis.