Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan-naproxen: two randomized controlled trials

Obstet Gynecol. 2009 Jul;114(1):106-113. doi: 10.1097/AOG.0b013e3181a98e4d.


Objective: To evaluate the efficacy and tolerability of sumatriptan-naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea.

Methods: Two replicate randomized, multicenter, double-blind, placebo-controlled, trials of adults with menstrual migraine and dysmenorrhea were conducted. Participants treated their menstrual migraine attack during the mild pain phase (within 1 hour of onset) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation (sumatriptan-naproxen) or placebo. The primary endpoint was 2-hour pain-free response.

Results: Sumatriptan-naproxen was statistically superior to placebo in both studies (n=311, Study 1; n=310, Study 2) for 2-hour and, 2- to 24-hour sustained pain-free response, use of headache and menstrual rescue medications, and several nonpain menstrual symptom categories. Two-hour pain-free rates were Study 1, 42% compared with 23%, and Study 2, 52% compared with 22%, P<.001. Two- to 24-hour sustained pain-free rates were Study 1, 29% compared with 18%, P=.022; Study 2, 38% compared with 10%, P<.001. Headache and menstrual medication rates were Study 1, 37% compared with 53%, P=.005; Study 2, 31% compared with 69%, P<.001. Women treated with sumatriptan-naproxen continued to be pain free through 48 hours compared with placebo: Study 1, 26% compared with 17%, P=.040; Study 2, 28% compared with 8%, P<.001. No serious adverse events were reported in either study; nausea and dizziness were the most frequently reported adverse events.

Conclusion: Sumatriptan-naproxen provided an effective pain-free response at 2 hours, which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea. Sumatriptan-naproxen was well-tolerated and resulted in decreased rescue medication use and relief of nonpainful menstrual symptoms.

Clinical trial registration:,, NCT00329459 and NCT00329355

Level of evidence: I.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Drug Combinations
  • Dysmenorrhea / complications*
  • Dysmenorrhea / drug therapy
  • Female
  • Humans
  • Migraine Disorders / drug therapy*
  • Naproxen / administration & dosage*
  • Sumatriptan / administration & dosage*


  • Drug Combinations
  • Naproxen
  • Sumatriptan

Associated data