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Geschlechterunterschiede in der Pharmakotherapie

Sex and gender differences in pharmacotherapy

Zusammenfassung

Arzneimittel wirken bei Männern und Frauen unterschiedlich. Biologische Unterschiede zwischen Männern und Frauen führen zu Unterschieden in der Pharmakokinetik, in der Arzneimittelresorption, in der Arzneimittelverteilung im Gewebe, in der Verstoffwechselung durch Leberenzyme, in der Ausscheidung durch die Niere und über den Darm. Darüber hinaus bestehen Geschlechterunterschiede in der Pharmakodynamik. Die biologischen Ursachen für diese Unterschiede liegen zum einen in der unterschiedlichen genetischen Ausstattung von Männern und Frauen, dann in unterschiedlichen epigenetischen Modifikationen und schließlich in der Wirkung von Sexualhormonen. Darüber hinaus spielt Gender als soziokulturelle Dimension von Geschlechterunterschieden in der Arzneimittelwirkung eine Rolle. Arzneimittel werden häufig nur an Tieren eines Geschlechts entwickelt und getestet entsprechend dem Vorurteil, dass Geschlechterunterschiede bei der klinischen Wirkung keine Rolle spielen. Auch in klinischen Studien wurden bislang die Geschlechterunterschiede häufig unterschätzt und Phase-III-Studien häufig nicht prospektiv darauf ausgelegt, Wirkungen bei Männern und Frauen zu erfassen. Hinzu kommt, dass Frauen und Männer Arzneimittel anders einnehmen. Ihre Compliance ist unterschiedlich, sie nehmen zusätzlich zu den verschriebenen Arzneimitteln unterschiedlich viele, möglicherweise interagierende, freiverkäufliche Substanzen ein. Weiter ist bekannt, dass Ärzte Frauen und Männer unterschiedlich intensiv behandeln. Fazit: Noch ist die Arzneimitteltherapie nicht für beide Geschlechter optimiert. Aber es besteht ein immer größeres Bewusstsein darüber, dass und welche Unterschiede zwischen Frauen und Männern beachtet werden müssen, um für beide Geschlechter optimale Arzneimittel in optimalen Dosierungen bereitzustellen.

Abstract

Many drugs have act differently in women and men. Biological differences between women and men lead to sex differences in pharmacokinetics, i.e., in drug absorption, distribution in tissues, metabolism by liver enzymes, and excretion via the kidney and intestine. In addition there are sex differences in pharmacodynamics, leading to a different efficacy of drugs in women and men. The biological differences between women and men may be caused by sex-specific gene expression, by sex-specific epigenetic modifications, and finally by the effect of sex hormones. In addition, gender plays a role in drug efficacy as a sociocultural dimension that may lead to differences between women and men. Frequently drugs are only tested on animals of one sex and thereby optimized for one sex. This is based on the notion that sex differences are not important for clinical drug effects. Furthermore, to date, sex and gender differences have been underestimated in clinical studies, and phase III studies were not prospectively designed to assess sex differences in drug effects. In addition, women and men use drugs differently with respect to compliance, adherence, and self-medication with over-the-counter drugs. Further, it is known that male and female physicians treat women and men as patients differently. In conclusion, drug therapy is not yet optimized for both genders. However, there is increasing awareness that differences between women and men should be respected in order to provide optimal drugs in optimal doses for both genders.

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Danksagungen

Dank gilt Herrn Frank Ording, Frau Stefanie Schmidt und Herrn Arne Kühne für die umfangreiche Mithilfe und sorgfältige Literaturrecherche.

Interessenkonflikt

V. Regitz-Zagrosek gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Regitz-Zagrosek, V. Geschlechterunterschiede in der Pharmakotherapie. Bundesgesundheitsbl. 57, 1067–1073 (2014). https://doi.org/10.1007/s00103-014-2012-6

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Schlüsselwörter

  • Sex
  • Gender
  • Stoffwechsel
  • Pharmakokinetik
  • Pharmakodynamik

Keywords

  • Sex
  • Gender
  • Metabolism
  • Pharmacokinetics
  • Pharmacodynamics