Objective: To examine the effect of sex on clinical response to triptans 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: Out of >1200 publications on clinical trials with triptans, 244 were identified with sex-related search terms. Only 19 publications presented sex-specific results, comprising n=2280 men and n=13899 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%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 due to 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 due to longer attack duration related to sex hormonal changes.