Exploring the therapeutic potential of disulfiram in endometriosis: mechanisms targeting inflammation, oxidative stress, pyroptosis, and angiogenesis.

Endometriosis (EMS) is a prevalent, inflammatory gynecological disorder with limited effective treatments and high recurrence rates. Given the central roles of inflammation, oxidative stress, pyroptosis, and angiogenesis in its pathogenesis, novel therapeutic strategies are urgently needed. This review aims to critically evaluate the potential of disulfiram (DSF), a repurposed antialcoholism drug, as a multifaceted therapeutic agent for EMS by analyzing its anti-inflammatory, antioxidant, anti-pyroptotic, and antiangiogenic properties. A comprehensive literature review was conducted. Scientific databases (e.g., PubMed, Web of Science) were systematically searched for pre-clinical and clinical studies investigating the mechanisms of EMS pathogenesis and the pharmacological actions of DSF. The analysis focused on synthesizing evidence linking DSF's known biological effects to the key pathological drivers of EMS. The analysis demonstrates that DSF and its metabolites target multiple pathways implicated in EMS. Evidence confirms DSF's potent inhibitory effects on key inflammatory mediators and signaling pathways (e.g., NLRP3 inflammasome-mediated pyroptosis). Furthermore, DSF enhances cellular antioxidant defenses, reduces reactive oxygen species, and suppresses angiogenic factors, thereby potentially disrupting the establishment and survival of endometriotic lesions. Disulfiram presents a promising, mechanistically grounded candidate for the treatment of endometriosis. Its unique ability to simultaneously modulate inflammation, oxidative stress, pyroptosis, and angiogenesis aligns closely with the multifactorial pathology of EMS. This review provides a strong rationale for future pre-clinical and clinical investigations to formally evaluate the efficacy and safety of DSF repurposing for this challenging disease.