The "double-edged sword" effect of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of endometriosis (EMS)

This study provides, for the first time, robust causal evidence from both genetic and structural biology perspectives for the "double-edged sword" attribute of NSAIDs in EMS, and proposes a new paradigm of "target-oriented heterogeneous effects." We found that specific NSAIDs might inadvertently promote disease progression by activating the EPHB4 pathway, while indomethacin stands out as a key exception due to its unique dual-action mechanism. These findings not only offer a critical explanation for the current clinical controversy but also lay a solid scientific foundation for advancing EMS management from "empirical medication" towards "precision-based selection guided by molecular mechanisms."