The influence of progesterone and estradiol upon migraine.

Abstract

The effect of progesterone and estradiol withdrawl upon menstrual migraine was examined in 8 regularly menstruating women (aged 23-45) who regularly suffered from migraine. The influence of estradiol alone was examined in 2 nonmenstruating women whose headaches had ended with cessation of menstruation. In 6 of the 8 regularly menstruating women determinations of hormonal level and migraine occurrence were made in a pre-treatment control cycle. It was found that migraine occurrence generally took place during or at the end of the phase of hormone withdrawl in a normal cycle. Progesterone was then administered intramuscularly to each woman in 25-75 mg doses 3-6 days before the expected onset of menstruation and continued until Day 2 in order to maintain the levels of progesterone that would normally occur at the middle of the luteal phase. Estradiol was administered in another cycle in single 10-20 mg doses in slow-release form. Hormone levels were measured daily. The 2 nonmenstruating women received single doses of estradiol. Progesterone treatment did not prevent the onset of migraine in 5 of the 6 women treated (though 1 of the 5 suffered a much less severe and shorter attack) and caused postponement of menstruation in 4 of the 6. In the estradiol cycle all 8 women had migraines delayed for 3-9 days. In 5 of 6 women tested the migraine occurred when the level of estradiol in the plasma dropped below 20 ng/100 ml. In the sixth woman a second injection of estradiol was given in an attempt to maintain a high level. This attempt failed and the migraine occurred despite the fact that the estradiol level was rising. The nonmenstruating women both experienced migraine. It appears that once estradiol withdrawl occurs the mechanism for migraine cannot be stopped. This suggests migraine might be initiated by the withdrawl of a metabolite of estradiol rather than by estradiol itself. The withdrawl of progesterone plays little if any part in the etiology of menstrual migraine.