New theories in the pathogenesis of menstrual migraine.

Hormonal and nonhormonal factors play a role in the pathophysiology of menstrual migraine, but estrogen withdrawal appears to be the most potent of these factors. It is postulated that estrogen withdrawal directly enhances excitability of trigeminal afferents, modulates the synthesis of neuropeptides, activates/deactivates specific neurotransmitter systems, and influences the function of microglia. These changes could activate and/or sensitize the trigeminal system and increase the likelihood of migraine headache during perimenstrual time periods. Three new theories are advanced in this article to explain the pathophysiology of menstrual migraine. Only through an understanding of the mechanisms involved in menstrual migraine can we gain insight into the management of this severe and debilitating form of migraine headache.