Sex Differences in Response to Triptans: A Systematic Review and Meta-analysis

Neurology. 2021 Jan 26;96(4):162-170. doi: 10.1212/WNL.0000000000011216. Epub 2020 Nov 18.


Objective: To examine the effect of sex on clinical response to triptans in migraine and to determine whether these differences are related to pharmacokinetics of triptans in men and women, we performed a systematic review and meta-analysis.

Methods: We searched clinical trials distinguishing clinical response to or pharmacokinetic parameters of triptans between sexes in PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science up to Dec 12, 2019. Analysis was based on data extracted from published reports. Male-to-female pooled risk ratios (RR) were calculated for clinical outcomes and pooled ratio of means (RoM) for pharmacokinetic outcomes using random-effects models.

Results: Of 1,188 publications on clinical trials with triptans, 244 were identified with sex-related search terms. Only 19 publications presented sex-specific results, comprising n = 2,280 men and n = 13,899 women. No sex differences were revealed for 2-hour headache and pain-free responses, but men had a lower risk for headache recurrence (male-to-female RR 0.64, 95% confidence interval [CI]: 0.55-0.76, Q = 0.81) and adverse events (RR 0.82, 95% CI: 0.72-0.93, Q = 4.93). Men had lower drug exposure with lower area under the curve (RoM 0.69, 95% CI: 0.60-0.81, Q = 18.06) and peak drug concentration (RoM 0.72, 95% CI: 0.64-0.82, Q = 8.24) than women.

Conclusions: Remarkably few publications about sex differences in triptan response are available. The limited number of eligible studies show sex differences in adverse event frequency, which may be partly because of drug exposure differences. This higher drug exposure in women is not reflected in different response rates. Despite higher exposure, women have higher headache recurrence rates possibly because of longer attack duration related to sex hormonal changes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Female
  • Humans
  • Male
  • Migraine Disorders / diagnosis*
  • Migraine Disorders / drug therapy*
  • Observational Studies as Topic / methods
  • Randomized Controlled Trials as Topic / methods
  • Recurrence
  • Sex Characteristics*
  • Treatment Outcome
  • Tryptamines / adverse effects
  • Tryptamines / therapeutic use*


  • Tryptamines