Beyond Lesions: A Systems Approach to Endometriosis and Pelvic Pain

Endometriosis is traditionally defined by the presence of lesions, yet compelling evidence challenges the lesion-centric model, especially for superficial lesions. Many patients experience pelvic pain, infertility, or immune dysfunction without significant lesions, while others have lesions without symptoms. This presentation explores endometriosis and persistent pelvic pain as overlapping syndromes mediated by neuroimmune dysregulation, altered microbiota, and environmental triggers such as bacterial endotoxins and endocrine disruptors. We will explore the role of the immune system, including macrophages and mast cells, in driving inflammation and lesion development, as well as the emerging evidence around intestinal permeability, bacterial contamination (e.g., LPS and Fusobacterium), and the gut-brain-immune axis. Treatment implications include dietary strategies, nervous system regulation, and evidence-informed use of natural antimicrobials such as berberine, NAC, and iodine. By moving beyond lesions, clinicians can adopt a more precise and compassionate approach to treating the whole person.

Learning Objectives

• Evaluate the limitations of the lesion-based paradigm of endometriosis in explaining persistent pelvic pain and infertility
• Describe the role of immune dysregulation—including macrophage and mast cell activation—in endometriosis pathophysiology
• Identify clinical strategies for supporting gut-immune-nervous system health in patients with suspected endometriosis or unexplained pelvic pain