Menstrual Migraines May Be Double the Trouble


LOS ANGELES — Migraine headaches were twice as likely during the menstrual cycle, and they lasted longer, were somewhat more painful, and proved significantly more resistant to treatment than migraines suffered during other times of the month, according to a study released at the annual meeting of the American Headache Society.

Dr. Brenda F. Pinkerman of the James A. Haley Veterans' Hospital in Tampa, Fla., reported a sharp spike in migraines on day 1 of the menstrual cycle in a prospective study of 107 women with a history of menstrual-related migraine.

The women were subjects in a larger study cosponsored by Ohio University in Athens and the National Institutes of Health. To be eligible, patients had to have a history of disabling migraines 3–20 days a month.

Those enrolled in the menstrual migraine portion of the study had a mean age of 35 and suffered from migraines a mean 9 days per month. The odds ratio of a migraine was 1.91—nearly a doubling of risk—in a 4-day window beginning 2 days prior to and ending 2 days after day 1 of the menstrual cycle, compared with any other time of the month.

Perimenstrual migraines were significantly different from those occurring at other times of the month in a number of ways, including the following:

▸ Duration: 23 hours vs. 16 hours

▸ Disability: occurring in conjunction with 86% of menstrual headaches vs. 76% of other headaches

▸ Doses of triptans: 2 vs. 1.6; and rescue medications: 2.3 vs. 1.7

▸ Pain-free response to medication at 2 hours: 7% vs. 13%

▸ Recurrence after 4 pain-free hours: 36%, compared with 20%

Other poster presentations at the meeting detailed the efficacy of rizatriptan administered early in the course of menstrual migraines and the safety and tolerability of frovatriptan taken prophylactically each month in women with regular menstrual cycles.

The TAME (Treat a Migraine Early) trials randomized 94 patients to take a single 10-mg dose of rizatriptan or placebo within 1 hour of the onset of any migraine occurring during the 2 days before to 3 days following day 1 of their menstrual cycles.

Freedom from pain at 2 hours was reported by 40 of 63 subjects (63.5%) taking rizatriptan, compared with 9 of 31 (29%) assigned to placebo, a highly significant difference. Nausea was significantly less common in subjects taking rizatriptan, although photophobia and phonophobia responses did not reach significance in the Merck-sponsored, multicenter study presented by Dr. Vincent Martin of the University of Cincinnati.

A final poster featured results from a yearlong, open-label extension study of frovatriptan used to prevent migraines in 308 patients with regular menstrual cycles and a history of menstrual migraine.

Women were instructed to take two 5-mg doses of frovatriptan 2 days prior to the expected onset of menstruation, followed by 2.5 mg of frovatriptan twice daily for the next 5 days. Dizziness, the most common side effect, occurred in about 7% of patients. The drug was well tolerated, with just 25 patients discontinuing long-term treatment for reasons other than migraine, reported Dr. Anne MacGregor of the City of London Migraine Clinic.

Perimenstrual migraines occurred in 44% of women taking prophylactic frovatriptan for a year—on par with the 41% who experienced perimenstrual migraines during a 3-month randomized, double-blind, placebo-controlled trial of 433 patients. In that pivotal study, 67% patients assigned to placebo experienced migraines.

The consistency of incidence data in the two trials suggests “durability of effect with continued use,” noted Dr. MacGregor and associates in their poster's conclusion.

The study was sponsored by Endo Pharmaceuticals of Chadds Ford, Pa., manufacturer of frovatriptan.

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