Testosterone, estradiol, and their ratio as predictors of migraine and premonitory symptoms in males

Abstract Background Hormonal imbalance has been proposed as a contributing factor in migraine pathophysiology in men. Alterations in free testosterone (Tf), estradiol (E2), and their ratio may influence migraine susceptibility and early attack manifestations. This study aimed to evaluate serum levels of free testosterone (Tf), estradiol (E2), in addition the Tf/E2 ratio in migraine men cases during interictal and ictal phases, and to assess their diagnostic performance in predicting migraine occurrence and premonitory symptoms. Methods In this case-control research, 25 male migraine cases and 25 age-matched healthy males were enrolled. Migraine diagnosis has been confirmed regarding ICHD-3 criteria. Clinical and reproductive histories were recorded, and androgen deficiency symptoms were assessed. Serum Tf and E2 levels were measured by chemiluminescent immunoassay during interictal and ictal phases in migraine patients, and once in controls. The Tf/E2 ratio was calculated. ROC curve analysis assessed predictive accuracy. Results Migraine patients showed significantly higher Tf and E2 levels during the ictal phase compared with interictal, and significantly lower Tf/E2 ratio ( p -value below 0.001). Interictal E2 and Tf/E2 ratio demonstrated moderate accuracy in predicting migraine (AUC = 0.752 and 0.702). Patients with premonitory symptoms had significantly higher Tf and E2 and lower Tf/E2 ratio in both phases ( p < 0.05). Interictal E2 showed high apparent predictive accuracy for premonitory symptoms (AUC = 1.0), suggesting potential as a biomarker. Conclusion Elevated estradiol and reduced Tf/E2 ratio are associated with migraine and premonitory symptoms in men. Hormonal profiling, particularly E2 levels and Tf/E2 ratio, may serve as valuable biomarkers for migraine prediction in males.