Endometriosis as a Model of Systemic Inflammation: Clinical, Molecular, and Translational Implications

Resumen

Endometriosis is increasingly recognized as a systemic inflammatory disease rather than a localized gynecological disorder. This review integrates recent molecular and clinical evidence demonstrating how chronic inflammation, oxidative stress, and extracellular vesicle (EV) signaling interact to shape both local and systemic pathophysiology. Elevated cytokines such as IL-1β, IL-6, TNF-α, IL-8, MCP-1, and VEGF sustain angiogenesis, immune activation, and lesion persistence, while diminished IL-10 impairs immunoregulation. Concurrently, oxidative stress arising from peritoneal iron overload and mitochondrial dysfunction amplifies inflammatory signaling through NF-κB and TGF-β/SMAD pathways, promoting fibrosis, apoptosis resistance, and nociceptor sensitization. Recent discoveries highlight EVs as mediators of systemic communication, transferring microRNAs and proteins that modulate immune, endothelial, and neural targets, thereby linking pelvic inflammation to cardiovascular, metabolic, and autoimmune comorbidities. Evidence from multiple studies indicates that endometriosis confers elevated risks of hypertension, dyslipidemia, autoimmune disorders, and mood disturbances—hallmarks of systemic immune and vascular dysregulation. Furthermore, chronic oxidative and inflammatory exposure fosters genomic instability, explaining the observed association with ovarian clear-cell and endometrioid carcinomas. Recognizing endometriosis as a multisystemic disorder supports the development of integrative diagnostic and therapeutic strategies, including cytokine and exosomal biomarker panels and targeted anti-inflammatory, antioxidant, and anti-angiogenic treatments. Contributions from Mexico, Colombia, and Ecuador emphasize the need for regionally inclusive research and precision-medicine approaches. Endometriosis thus emerges as a model of systemic inflammation, exemplifying how immune, oxidative, and endocrine networks converge to produce both reproductive and extra-pelvic disease manifestations.