Sex Differences in Response to Triptans

Neurology, vol. 96, pp. 162–170

Abstract

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.

Authors 5

1. Daphne S. van Casteren Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Internal Medicine

   Leiden University Medical Center · Erasmus MC · Charité - Universitätsmedizin Berlin · Erasmus University Rotterdam

   Affiliation as printed

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Internal Medicine (A.H.J.D., A.M.V.D.B.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

2. Tobias Kurth Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Internal Medicine

   Leiden University Medical Center · Erasmus MC · Charité - Universitätsmedizin Berlin · Erasmus University Rotterdam

   Affiliation as printed

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Internal Medicine (A.H.J.D., A.M.V.D.B.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

3. A.H. Jan Danser Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Internal Medicine

   Leiden University Medical Center · Erasmus MC · Charité - Universitätsmedizin Berlin · Erasmus University Rotterdam

   Affiliation as printed

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Internal Medicine (A.H.J.D., A.M.V.D.B.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

4. Gisela Marie Terwindt Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Internal Medicine

   Leiden University Medical Center · Erasmus MC · Charité - Universitätsmedizin Berlin · Erasmus University Rotterdam

   Affiliation as printed

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Internal Medicine (A.H.J.D., A.M.V.D.B.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

5. Antoinette MaassenVanDenBrink Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Internal Medicine

   Leiden University Medical Center · Erasmus MC · Charité - Universitätsmedizin Berlin · Erasmus University Rotterdam

   Affiliation as printed

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Internal Medicine (A.H.J.D., A.M.V.D.B.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   Department of Neurology (G.M.T.), Leiden University Medical Center, Leiden, The Netherlands

   From the Department of Internal Medicine (D.S.v.C.), Erasmus University Medical Center, Rotterdam and Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands