Endometriosis pathophysiology and biomarkers: a review of immunological, genetic, hormonal, and metabolic mechanisms

Abstract

Endometriosis is a multifactorial disease characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pain and infertility. Its pathophysiology involves complex interactions between immune dysfunction, genetic and epigenetic alterations, hormonal imbalance, oxidative stress, and microbiota dysbiosis, which drive inflammation and ectopic tissue growth. Understanding these mechanisms is essential for identifying potential biomarkers and developing effective therapeutic strategies. This narrative review synthesizes evidence from 105 English-language studies published between 2012 and 2025 and identified through searches in PubMed, Scopus, MEDLINE, and Google Scholar using Medical Subject Headings terms and Boolean operators. Findings were grouped into five domains: immune dysfunction, genetic and epigenetic factors, oxidative stress, hormone dysregulation, and microbiota. Immune alterations contribute to chronic inflammation, lesion persistence, and oxidative stress. Genetic and epigenetic changes, including DNA methylation and microRNA dysregulation, affect hormonal regulation. Circulating cell-free DNA has emerged as a promising diagnostic biomarker, and the microbiota modulates immune responses and oxidative stress, influencing disease progression. Integrating these domains provides a comprehensive framework for understanding endometriosis and highlights opportunities for biomarker development and novel therapies. Advances in diagnostic tools and targeted interventions may improve early detection, reduce recurrence, support fertility preservation, and facilitate personalized management of the disease.