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Geschlechterunterschiede in der Pharmakotherapie

Sex and gender differences in pharmacotherapy

  • Leitthema
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

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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Literatur

  1. Regitz-Zagrosek V, Seeland U (2012) Sex and gender differences in clinical medicine. Handb Exp Pharmacol 214:3–22

  2. Seeland U, Regitz-Zagrosek V (2012) Sex and gender differences in cardiovascular drug therapy. Handb Exp Pharmacol 214:211–236

  3. Oertelt-Prigione S, Regitz-Zagrosek V (2009) Gender aspects in cardiovascular pharmacology. J Cardiovasc Transl Res 2:258–266

    Article  PubMed  Google Scholar 

  4. Spoletini I, Vitale C, Malorni W, Rosano G (2012) Sex differences in drug effects: interaction with sex hormones in adult life. In: Regitz-Zagrosek V (Hrsg) Sex and gender differences in pharmacology. Springer, Berlin Heidelberg New York Tokyo, S 91–106

  5. Regitz-Zagrosek V (2006) Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nat Rev Drug Discov 5:425–438

    Article  CAS  PubMed  Google Scholar 

  6. Everson GT (1992) Gastrointestinal motility in pregnancy. Gastroenterol Clin North Am 21:751–776

    CAS  PubMed  Google Scholar 

  7. Soldin OP, Mattison DR (2009) Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 48:143–157

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Franconi F, Carru C, Malorni W, Vella S, Mercuro G (2011) The effect of sex/gender on cardiovascular pharmacology. Curr Pharm Des 17:1095–1107

    Article  CAS  PubMed  Google Scholar 

  9. Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler UH, Kuhl H (2003) Effect of four different oral contraceptives on various sex hormones and serum-binding globulins. Contraception 67:25–32

    Article  CAS  PubMed  Google Scholar 

  10. Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V (2005) Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur Heart J 26:1585–1595

    Article  CAS  PubMed  Google Scholar 

  11. Rathore SS, Wang Y, Krumholz HM (2002) Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 347:1403–1411

    Article  CAS  PubMed  Google Scholar 

  12. Viegas VU, Liu ZZ, Nikitina T, Perlewitz A, Zavaritskaya O, Schlichting J, Persson PB, Regitz-Zagrosek V, Patzak A, Sendeski MM (2012) Angiotensin II type 2 receptor mediates sex differences in mice renal interlobar arteries response to angiotensin II. J Hypertens 30:1791–1798

    CAS  PubMed  Google Scholar 

  13. Sandberg K, Ji H (2012) Sex differences in primary hypertension. Biol Sex Differ 3:7

    Article  PubMed Central  PubMed  Google Scholar 

  14. Karatas A, Hegner B, de Windt LJ, Luft FC, Schubert C, Gross V, Akashi YJ, Gurgen D, Kintscher U, da Costa Goncalves AC, Regitz-Zagrosek V, Dragun D (2008) Deoxycorticosterone acetate-salt mice exhibit blood pressure-independent sexual dimorphism. Hypertension 51:1177–1183

    Article  CAS  PubMed  Google Scholar 

  15. Herrmann SM, Nicaud V, Schmidt-Petersen K, Pfeifer J, Erdmann J, McDonagh T, Dargie HJ, Paul M, Regitz-Zagrosek V (2002) Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies. Eur J Heart Fail 4:707–712

    Article  CAS  PubMed  Google Scholar 

  16. Gerdts E, Okin PM, de Simone G, Cramariuc D, Wachtell K, Boman K, Devereux RB (2008) Gender differences in left ventricular structure and function during antihypertensive treatment: the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension 51:1109–1114

    Article  CAS  PubMed  Google Scholar 

  17. Petrov G, Regitz-Zagrosek V, Lehmkuhl E, Krabatsch T, Dunkel A, Dandel M, Dworatzek E, Mahmoodzadeh S, Schubert C, Becher E, Hampl H, Hetzer R (2010) Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Circulation 122:23–28

    Article  Google Scholar 

  18. Potapov E, Schweiger M, Lehmkuhl E, Vierecke J, Stepanenko A, Weng G, Pasic M, Huebler M, Regitz-Zagrosek V, Hetzer R, Krabatsch T (2012) Gender differences during mechanical circulatory support. ASAIO J 58:320–325

    Article  PubMed  Google Scholar 

  19. Drici MD, Knollmann BC, Wang WX, Woosley RL (1998) Cardiac actions of erythromycin: influence of female sex. JAMA 280:1774–1776

    Article  CAS  PubMed  Google Scholar 

  20. Woosley RL, Chen Y, Freiman JP, Gillis RA (1993) Mechanism of the cardiotoxic actions of terfenadine. JAMA 269:1532–1536

    Article  CAS  PubMed  Google Scholar 

  21. Mahmoodzadeh S, Dworatzek E, Fritschka S, Pham TH, Regitz-Zagrosek V (2010) 17beta-estradiol inhibits matrix metalloproteinase-2 transcription via map kinase in fibroblasts. Cardiovasc Res 85:719–728

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Nordmeyer J, Eder S, Mahmoodzadeh S, Martus P, Fielitz J, Bass J, Bethke N, Zurbrugg HR, Pregla R, Hetzer R, Regitz-Zagrosek V (2004) Upregulation of myocardial estrogen receptors in human aortic stenosis. Circulation 110:3270–3275

    Article  CAS  PubMed  Google Scholar 

  23. Regitz-Zagrosek V, Schubert C, Kruger S (2008) Sex differences in cardiovascular drug targeting. Internist 49:1383–1386, 1388–1390

    Article  CAS  PubMed  Google Scholar 

  24. Simon T, Mary-Krause M, Funck-Brentano C, Jaillon P (2001) Sex differences in the prognosis of congestive heart failure: results from the cardiac insufficiency bisoprolol study (CIBIS II). Circulation 103:375–380

    Article  CAS  PubMed  Google Scholar 

  25. Ghali JK, Pina IL, Gottlieb SS, Deedwania PC, Wikstrand JC, MERIT-HF Study Group (2002) Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Circulation 105:1585–1591

    Article  CAS  PubMed  Google Scholar 

  26. Garg R, Yusuf S (1995) Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 273:1450–1456

    Article  CAS  PubMed  Google Scholar 

  27. Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ, Second Australian National Blood Pressure Study Group (2003) A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 348:583–592

    Article  CAS  PubMed  Google Scholar 

  28. Mackay FJ, Pearce GL, Mann RD (1999) Cough and angiotensin II receptor antagonists: cause or confounding? Br J Clin Pharmacol 47:111–114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Abi-Gerges N, Philp K, Pollard C, Wakefield I, Hammond TG, Valentin JP (2004) Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes. Fundam Clin Pharmacol 18:139–151

    Article  CAS  PubMed  Google Scholar 

  30. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE (2005) A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 352:1293–1304

    Article  CAS  PubMed  Google Scholar 

  31. Arnold AP, Chen X, Itoh Y (2012) What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation. Handb Exp Pharmacol 214:67–88

  32. Xu J, Deng X, Disteche CM (2008) Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain. PloS One 3:e2553

    Article  PubMed Central  PubMed  Google Scholar 

  33. Queiros AM, Eschen C, Fliegner D, Kararigas G, Dworatzek E, Westphal C, Sanchez Ruderisch H, Regitz-Zagrosek V (2013) Sex- and estrogen-dependent regulation of a mirna network in the healthy and hypertrophied heart. Int J Cardiol 169:331–338

    Article  PubMed  Google Scholar 

  34. Raz L, Miller VM (2012) Considerations of sex and gender differences in preclinical and clinical trials. Handb Exp Pharmacol 214:127–147

  35. Enserink M (2005) Let’s talk about sex – and drugs. Science 308:1578

    Article  CAS  PubMed  Google Scholar 

  36. Anonymous (2010) Putting gender on the agenda. Nature 465:665

  37. Pollitzer E (2013) Biology: cell sex matters. Nature 500:23–24

    Article  CAS  PubMed  Google Scholar 

  38. Karbwang J, Torres C (2011) Ethical issues related to clinical trials outside the International Conference on Harmonization regions. Future Med Chem 3:1457–1460

    Article  CAS  PubMed  Google Scholar 

  39. Daly C, Clemens F, Lopez Sendon JL, Tavazzi L, Boersma E, Danchin N, Delahaye F, Gitt A, Julian D, Mulcahy D, Ruzyllo W, Thygesen K, Verheugt F, Fox KM, Euro Heart Survey Investigators (2006) Gender differences in the management and clinical outcome of stable angina. Circulation 113:490–498

    Article  PubMed  Google Scholar 

  40. Baumhakel M, Muller U, Bohm M (2009) Influence of gender of physicians and patients on guideline-recommended treatment of chronic heart failure in a cross-sectional study. Eur J Heart Fail 11:299–303

    Article  PubMed Central  PubMed  Google Scholar 

  41. Geller JC, Cassens S, Brosz M, Keil U, Bernarding J, Kropf S, Bierwirth RA, Lippmann-Grob B, Schultheiss HP, Schluter K, Pels K (2007) Achievement of guideline-defined treatment goals in primary care: the German Coronary Risk Management (CoRiMa) study. Eur Heart J 28:3051–3058

    Article  CAS  PubMed  Google Scholar 

  42. Journath G, Hellenius ML, Petersson U, Theobald H, Nilsson PM, Hyper-Q Study Group Sweden (2008) Sex differences in risk factor control of treated hypertensives: a national primary healthcare-based study in Sweden. Eur J Cardiovasc Prev Rehabil 15:258–262

    Article  PubMed  Google Scholar 

  43. Gouni-Berthold I, Berthold HK (2012) Role of physician gender in drug therapy. Handb Exp Pharmacol 214:183–208

  44. Hofer-Duckelmann C (2012) Gender and polypharmacotherapy in the elderly: a clinical challenge. Handb Exp Pharmacol 214:169–182

  45. Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD (1998) Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol 46:505–511

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Thurmann PA, Haack S, Werner U, Szymanski J, Haase G, Drewelow B, Reimann IR, Hippius M, Siegmund W, May K, Hasford J (2006) Tolerability of beta-blockers metabolized via cytochrome P450 2D6 is sex-dependent. Clin Pharmacol Ther 80:551–553

    Article  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

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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  1. Institut für Geschlechterforschung in der Medizin (GIM), Charité-Universitätsmedizin Berlin, Hessische Straße 3–4, 10115, Berlin, Deutschland

    V. Regitz-Zagrosek

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Correspondence to V. Regitz-Zagrosek.

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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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