Hormonal Dysregulation and Neuroinflammation in Endometriosis: Convergent Druggable Pathways
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This review synthesizes evidence on the reciprocal interaction between hormonal dysregulation and neuroinflammation in endometriosis, identifying convergent druggable pathways that explain disease persistence and symptoms.
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Abstract
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.
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Cited by (2)
- Peritoneal Incretin Deficiency and Tirzepatide as a Multi-Axis Adjuvant Hypothesis in Treatment-Refractory Endometriosis: A Mechanistic Framework Linking Metabolism, Immunity, Fibrosis, and Nociception 2026
- Neuroimmune fitness in endometriosis: decoding the adaptive neural circuits that sustain lesion persistence, fibrosis, and chronic pain 2026
Source provenance
- europepmc
- last seen: 2026-10-12T06:17:10.165071+00:00
- openalex
- last seen: 2026-08-18T06:03:38.117434+00:00
- pubmed
- last seen: 2026-10-12T06:10:41.828919+00:00
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