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Controlling Estrogen Levels May Treat Menstrual Migraine

A 20-µg decrease in dose of ethinyl estradiol may be enough to cause a migraine attack.


ASHEVILLE, NC—Menstrual-related migraine (MRM) can be particularly disabling and is difficult to treat using conventional migraine medications. To reduce the risk of MRM, a patient’s decrease in estrogen levels on the days around menses onset must be limited to 10 µg of ethinyl estradiol or less, said Anne H. Calhoun, MD, Professor of Anesthesiology and Psychiatry at the University of North Carolina and Partner and Cofounder of the Carolina Headache Institute in Durham, North Carolina.

“Most migraineurs by far are women, and as such, most migraineurs have MRM,” she said. “Nearly two-thirds of migraineurs have hormonal triggers, and it is our job to help our patients cope with them.”

Anne H. Calhoun, MD

Peak Times for Headache Occurrence

MRM occurrence correlates with days during a woman’s menstrual cycle, Dr. Calhoun said at the Eighth Annual Scientific Meeting of the Southern Headache Society. A study of diary data from 155 women found a 50% increased likelihood of migraine during the five days before menses, compared with all other times during the cycle.

“However, during the five days after the onset of bleeding, there was a 2.5 times increased risk of migraine,” Dr. Calhoun said. “Analysis of an even narrower time frame—two days before and after the onset of menses—shows a three to nearly five times increased migraine risk.” The pain was twice as likely to be considered severe two days before menses and more than three times as likely to be considered severe during the first three days of menstruation, she added.

Conventional migraine therapy may have limited efficacy for the treatment of MRM, Dr. Calhoun suggested. For example, one retrospective analysis examined data from two randomized trials of oral rizatriptan. In a subgroup of 335 women with MRM, 68% of women taking rizatriptan 10 mg and 70% of women taking rizatriptan 5 mg experienced pain relief, compared with 44% of women taking placebo. “However, for women who used the treatment on the day of bleeding, the response was about the same as placebo,” she said.

Hormonal Fluctuations Associated With Migraine

Fluctuations in estrogen levels are key to why migraine is more likely at certain times during a woman’s cycle, Dr. Calhoun said. She cited a study of 81 menstruating women with clinically diagnosed migraine that assessed their risk of tension-type headache and migraine with and without aura. There was a significantly elevated risk of tension-type headache and migraine without aura on the first two days of menses and a significantly higher risk of migraine without aura during the two days before menses onset. Furthermore, there was a significantly lower risk of all headache types around the time of ovulation.

“I looked at the data from this study and used the information differently,” Dr. Calhoun said. “In this same population of migraineurs, I added all their headaches together for each day and discovered that there was an increase in headache frequency when estrogen levels were low.”

When estrogen levels decrease, monoamine oxidase increases, serotonin and β-endorphin levels decrease, and serotonergic postsynaptic responsiveness and neurotransmitter uptake decrease. “In addition, there is an increase in calcitonin gene-related peptide concentrations,” Dr. Calhoun said. “This is why menstrual migraine is so much more intense than … non-MRM.”

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