Targeting Oxidative Stress Involved in Endometriosis and Its Pain Original paper

What was reviewed?

This review examined how oxidative stress drives the development, progression, and pain of endometriosis, with a central focus on redox imbalance, inflammation, iron dysregulation, and ferroptosis. The authors synthesized biochemical, cellular, animal, and clinical evidence showing that excess reactive oxygen species overwhelm antioxidant defenses such as glutathione systems, leading to lipid peroxidation, cytokine activation, angiogenesis, and ectopic lesion survival. The review also evaluated therapeutic strategies that target oxidative stress, including antioxidants, redox-active compounds, and lifestyle interventions, while linking these pathways to chronic pelvic pain and disease severity.

Who was reviewed?

The review drew on studies involving women of reproductive age diagnosed with endometriosis, along with supporting data from rodent models, in vitro endometrial cell systems, and biochemical assays. It incorporated evidence from peritoneal fluid, serum, eutopic and ectopic endometrial tissues, and immune cell studies. The authors also reviewed emerging work that examined gut microbial changes in animal models and human observational studies, although this evidence remained limited and exploratory rather than definitive.

Most important findings

The review established oxidative stress as a core driver of endometriosis pathology. Elevated reactive oxygen species, iron overload, and reduced antioxidant capacity promoted inflammation, extracellular matrix remodeling, angiogenesis, and lesion persistence. Macrophage activation and NF-κB signaling amplified cytokine release and pain-inducing prostaglandins. Ferroptosis emerged as a key mechanism linked to glutathione depletion and lipid peroxidation. Importantly, the review reported emerging associations between endometriosis and gut microbiome alterations. Animal studies showed that endometriosis induction altered gut microbial diversity over time, while oral antibiotics reduced lesion progression. Specific microbial-related findings included beneficial effects of Lactobacillus supplementation through IL-12 induction and reduced lesion growth, and inhibition of lesion progression by the gut-derived metabolite n-butyrate, linking microbial metabolites to reduced inflammation and oxidative stress.

Key implications

This review reframes endometriosis as a systemic oxidative and inflammatory disorder rather than a purely gynecologic condition. Targeting oxidative stress, glutathione pathways, iron metabolism, and immune activation may offer disease-modifying strategies beyond hormonal suppression. The emerging microbiome findings suggest that gut microbial modulation could complement antioxidant therapies by reducing inflammation and oxidative injury. For clinicians, the review supports integrated approaches that address redox imbalance, immune activation, pain mechanisms, and potentially microbiome-related pathways to improve symptom control and quality of life in endometriosis patients.