PO-24 | Inflammatory signatures of comorbid episodic migraine and endometriosis: a cytokine-based analysis

Maria Albanese,^1,2 Veronica Ceci,^3,4 Giulia Carrera,^4,5 Aikaterini Selntigia,⁶ Caterina Exacoustos,⁶ Marta Tiberi,⁴ Stefano Saracini,^3,4 Alessandro Matteocci,^4,7 Nicola Biagio Mercuri,^1,2,8 Valerio Chiurchiù^3,4 | ¹Department of Systems Medicine, University of Rome Tor Vergata, Rome; ²Regional Referral Headache Center, Neurology Unit, Tor Vergata University Hospital, Rome; ³Institute of Translational Pharmacology, National Research Council of Italy (CNR), Rome; ⁴Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome; ⁵PhD Program in Neuroscience, Department of Systems Medicine, University of Rome Tor Vergata, Rome; ⁶Department of Surgical Sciences, Gynecological Unit, University of Rome Tor Vergata, Rome; ⁷PhD program in Immunology, Molecular Medicine and Applied biotechnologies, University of Rome Tor Vergata, Rome; ⁹Laboratory of Experimental Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy

Background: Migraine and endometriosis are two chronic, often comorbid conditions that significantly affect women’s health. While both are influenced by hormonal factors, mounting evidence points to systemic inflammation as a shared pathophysiological mechanism; yet the biological link between them has remained elusive. This study explored inflammatory cytokine profiles in women with migraine, endometriosis, or both, and their association with symptom severity and functional impact.

Methods: We enrolled female patients admitted to the Endometriosis Unit and the Headache Center of Tor Vergata University Hospital of Rome and diagnosed with only episodic migraine, with only endometriosis or with concomitant episodic migraine and endometriosis. Pro-inflammatory cytokines were measured in plasma and correlations with clinical parameters were performed.

 Results: Women with episodic migraine showed elevated circulating levels of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), compared to healthy controls. These inflammatory markers were even more pronounced in participants with both migraine and endometriosis, pointing to a synergistic effect of the two conditions on systemic inflammation. IL-1β levels correlated strongly with headache frequency and disability scores, while IL-6 and TNF-α were associated with both migraine severity and pelvic pain. Women with endometriosis alone did not exhibit comparable cytokine elevations, suggesting that inflammation is uniquely amplified in the presence of comorbidity. In parallel, changes in leukocyte distribution, including a higher neutrophil-to-lymphocyte ratio, further supported a state of immune activation exclusive to the comorbid group.

Conclusion: These findings provide the first biological evidence of a shared inflammatory endotype in women suffering from both migraine and endometriosis that may contribute to the increased symptom burden and their comobrbidity, underscoring the need for integrative approaches in diagnosis and management.