Inflammatory cytokine signatures are associated with disease burden and comorbidity of episodic migraine and endometriosis

Objectives – The aim of this study was to characterize inflammatory cytokine profiles in women diagnosed with episodic migraine, endometriosis, or both conditions and to determine how these cytokine patterns relate to symptom severity and functional impact, to identify potential biological markers distinguishing comorbid cases from single-diagnosis cases.Methods – Female patients with only episodic migraine, only endometriosis, or both conditions were enrolled. Plasma levels of proinflammatory cytokines were measured, and correlations with clinical parameters were analyzed.Results – Women with episodic migraine had elevated levels of IL-1β, IL-6, and TNF-α compared with healthy controls, with even higher levels in those with both migraine and endometriosis, indicating a synergistic effect on systemic inflammation. IL-1β correlated with headache frequency and disability while IL-6 and TNF-α were linked to migraine severity and pain. Women with endometriosis alone did not show similar cytokine elevations, suggesting that inflammation is particularly amplified in comorbidity. Changes in leukocyte distribution further supported a unique immune activation profile in the comorbid group.Discussion – These findings reveal novel biological evidence of a shared inflammatory endotype in women suffering from both conditions, which may contribute to the increased burden and comorbidity, highlighting the need for integrative diagnostic and management approaches.