Sex differences in response to triptans: a systematic review and meta-analysis

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.