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January 26, 2021; 96 (4) Views & Reviews

Sex Differences in Response to Triptans

A Systematic Review and Meta-analysis

Daphne S. van Casteren, View ORCID ProfileTobias Kurth, A.H. Jan Danser, Gisela M. Terwindt, Antoinette MaassenVanDenBrink
First published November 18, 2020, DOI: https://doi.org/10.1212/WNL.0000000000011216
Daphne S. van Casteren
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.
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Tobias Kurth
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.
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  • ORCID record for Tobias Kurth
A.H. Jan Danser
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.
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Gisela M. Terwindt
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.
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Antoinette MaassenVanDenBrink
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.
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Citation
Sex Differences in Response to Triptans
A Systematic Review and Meta-analysis
Daphne S. van Casteren, Tobias Kurth, A.H. Jan Danser, Gisela M. Terwindt, Antoinette MaassenVanDenBrink
Neurology Jan 2021, 96 (4) 162-170; DOI: 10.1212/WNL.0000000000011216

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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.

Glossary

CI=
confidence interval;
RR=
risk ratio;
RoM=
ratio of mean

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Equal author contributions: Gisela M Terwindt and Antoinette MaassenVanDenBrink are shared last author.

  • Received April 3, 2020.
  • Accepted in final form September 25, 2020.
  • © 2020 American Academy of Neurology
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