Endometriosis Awareness Month
Endometriosis is a debilitating complex disease where endometrial-like cells grow on organs outside of the uterus and which has been underrepresented in research, undertreated, and underdiagnosed. 190 million, or one in ten women of reproductive age lives with it, yet diagnosis still takes an average of seven to ten years. Our latest research is changing how science understands it, and the findings are reshaping how we think about its causes.
We conducted a genome-wide association study, which scans hundreds of thousands of genetic markers across the entire human genome to find variations linked to a specific disease. Our study involved 1.4 million women (over 105,000 cases). For the first time, we included all global population groups – African, East Asian, European, Latin American, Middle Eastern, and South Asian individuals – as research traditionally only included European individuals. We identified 80 genetic variants significantly associated with endometriosis, 37 of which had never been linked to the disease before. We also confirmed five genetic variants for adenomyosis, a related condition where endometrial tissue grows into the muscular wall of the uterus. Using molecular integration, combining genetic, protein, and epigenetic data, we traced how these variants biologically affect the body. The evidence converges on three major biological pathways: immune regulation, tissue remodeling, and cell differentiation. In plain terms, endometriosis is not simply a hormonal problem. It involves how the immune system fails to clear misplaced tissue, how cells invade and reshape their environment, and how gene activity is regulated across the uterus, ovaries, colon, and even breast tissue.
Our results suggest molecular support for several leading theories of endometriosis pathogenesis simultaneously, including benign metastasis, dysregulated immune system, abnormal cell cycle and differentiation, impaired apoptosis (the process by which damaged cells are cleared), inflammation, hormonal imbalance, vascular dissemination (endometrial-like cells traveling through the vascular or lymphatic system), and epigenetic alterations. The evidence points not to a single cause, but to the convergence of multiple mechanisms acting simultaneously with considerable variation between patients, which would explain why no single treatment has ever worked for everyone and why integrative, multi-target approaches are essential.
We also developed a polygenic risk score, a single score calculated from thousands of genetic variants that estimates a person’s inherited likelihood of developing endometriosis. Women in the highest genetic risk category were up to twice as likely to be diagnosed compared to those in the lowest. While not yet ready for clinical use, this lays the groundwork for future early-detection strategies and precision medicine, where a woman’s genetic and clinical profile could one day guide how her disease is identified and treated. Our analyses also flagged breast cancer drugs as statistically promising candidates for repurposing as endometriosis treatments, alongside two progestins already used in gynecological care. These are not yet clinical recommendations, but they represent a scientifically grounded shortlist for future trials.
For millions of women still waiting for answers, the endometriosis map is finally getting sharper.
Ramon y Cajal senior research fellow at the Women and Perinatal Health Research Group in Hospital Sant Pau and research affiliate at Yale University. Her research focuses on the genetic and epidemiological overlap between psychiatric traits and physical health, with a particular interest in chronic pain and endometriosis using advanced statistical analyses. She investigates shared biological mechanisms to identify clinically actionable findings that can inform prevention and personalized treatment strategies. She is especially committed to advancing women’s health research through translational and interdisciplinary approaches.