Although 70 percent of the most severe migraines experienced by women are premenstrual, less than 7 percent of these women report migraine exclusively at the onset of menstruation. We proposed the mechanism of action was by preventing the luteal phase rise and then fall in estrogen. However, danazol has multiple modes of action including its androgenic effect and its ability to bind to various intracellular androgen, progesterone, glucocorticoid, and estrogen receptors. Therefore, the direct action of danazol on estrogen levels may or may not be the proposed true mode of action on these women's migraines. The plan called for using the GNRHagonists in injectable form, initially for 2 months, and subsequently for up to one year in those who remained relatively migraine-free.
Migraine refers to a specific type of severe headache.
Migraine, by definition, cannot be associated with any physical or organic lesion. These patients were selected based on their failure to respond to all previous medication trials. Each woman had experienced more than one day of severe and incapacitating migraines per month at the onset of menstruation over the preceding 5 years and had been seen in emergency departments at least four times in the previous 12 months. The human subject Institutional Review Broad of Providence Hospital, Southfield, Michigan, approved the study design and method. Each participant completed a written informed consent form prior to her enrollment.