Decreases in Hormone Levels Modulate Neurovascular Coupling but Not Reduced Insular Functional Connectivity in Menstrual-Related Migraine.

Menstrual-related migraine (MRM) is a neurovascular disorder associated with decreased sex hormone levels. The menstrual cycle influences both cerebrovascular function and functional brain connectivity, with accumulating evidence linking migraine to altered connectivity, particularly in the insula. However, the neuropathological mechanisms underlying MRM during the menstrual cycle remain poorly understood. In this longitudinal study, 36 MRM patients and 29 healthy controls were recruited. Sex hormone levels and resting-state functional magnetic resonance imaging (fMRI) were collected during both the late-follicular phase (LFP) and the perimenstrual phase (PMP). Neurovascular function was assessed using voxel-wise hemodynamic response function (HRF) parameters. The subregions of insula-to-whole-brain phase synchronization were estimated using the HRF variations corrected phase information. Our results showed that hormone level decreases from the LFP to the PMP modulated HRF response heights. Changes in the HRF width were reversed between MRM patients and controls, with hormone fluctuations particularly affecting the superior temporal gyrus in the MRM group. Additionally, MRM patients exhibited increased insular phase synchronization in the LFP and reduced synchronization in the PMP. These findings suggest that menstrual cycle-related hormone fluctuations contribute to dysregulated neurovascular coupling in MRM. The reduced insular phase synchronization in the PMP may not be directly driven by these hormone changes.