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Analysis Highlights Need for Female-Specific Migraine Treatments


Results of an e-diary study compare symptoms of perimenstrual and nonperimenstrual migraine attacks among women.

The longer duration of perimenstrual migraine attacks in women with menstrually related migraine (MRM) is associated with a higher risk of recurrence and increased triptan use, according to results of an electronic diary (e-diary) study.

Findings, published in Neurology, indicate a potential higher risk of medication overuse in this patient population and underscore the need to develop female-specific prophylactic treatments, authors wrote.

Although the exact underlying cause of migraine is unknown, both endogenous and exogenous female sex hormones are considered important contributors to the condition’s pathophysiology, and menstruation serves as the most reported migraine trigger factor for women.

In addition, “migraine prevalence strongly increases in women after menarche, and attack frequency notably changes during hormonal milestones, such as pregnancy and menopause,” researchers said. Some studies have also pointed to the role reduced estrogen levels play in migraine attacks.

To better understand perimenstrual (occurring immediately before and during menstruation) and nonperimenstrual migraine attack characteristics and to assess premenstrual syndrome (PMS) in women with MRM, investigators conducted a prospective e-diary study.

A total of 500 Dutch migraineurs, between ages 18 and 80 years, completed the headache e-diary for at least 1 month between February 2019 and October 2020. Any pregnant, breastfeeding, or postmenopausal women were excluded from the study, in addition to those using continuous sex hormonal therapies.

“In total 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria,” authors wrote.

Analyses revealed perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with:

  • Longer duration (20 vs 16.1 hours; 95% CI, 0.2-0.4)
  • Higher recurrence risk (odds ratio [OR], 2.4; 95% CI, 2.0-2.9)
  • Increased triptan intake (OR, 1.2; 95% CI, 1.1-1.4)
  • Higher headache intensity (OR, 1.4; 95% CI, 1.2-1.7)
  • Less pain coping (mean difference, –0.2; 95% CI, –0.3 to –0.1)
  • More pronounced photophobia (OR, 1.3; 95% CI, 1.2-1.4) and phonophobia (OR, 1.2; 95% CI, 1.1-1.4)
  • Less aura (OR, 0.8; 95% CI, 0.6-1.0)

In addition, data showed differences in attack characteristics were more pronounced when focusing on women with MRM, while prevalence of PMS was not different for women with MRM compared with non-MRM (11% vs 15%), researchers said.

Overall, the average attack duration of a perimenstrual migraine was 35% longer than nonperimenstrual attacks, after correcting for confounders (P < .001). These migraines were more severe than nonperimenstrual attacks, “due to a higher recurrence risk after triptan intake with no difference in 2-hour headache and pain free response.”

As an overlap in symptomology exists between PMS and the prodromal phase of migraine, it is possible women with MRM may have found it difficult to differentiate between these 2 conditions.

Subgroup analyses were not performed for women who took preventive medications, marking a limitation to the study.

Findings support the fact that “women with MRM are at increased risk for medication overuse,” authors concluded.

“The long duration of perimenstrual migraine attacks with a high risk of recurrence highlights the need to improve understanding of the role of sex hormones in the provocation of attacks in women with migraine. Ultimately, this knowledge will contribute to the development of an urgently needed female-specific prophylactic treatment intervening with sex hormones.”


van Casteren DS, Verhagen IE, van der Arend BWH, van Zwet EW, MaassenVanDenBrink A, Terwindt GM. Comparing perimenstrual and nonperimenstrual migraine attacks using an e-diary. Neurology. Published online September 7, 2021. doi:10.1212/WNL.0000000000012723

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