Skip to main content

Women encounter ADRs more often than do men



Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs.


A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database—KLASSE.


In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31–1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15–3.19; p = 0.012).


Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.

This is a preview of subscription content, access via your institution.


  1. 1.

    Bowman L, Carlstedt BC, Hancock EF, Black CD (1996) Adverse drug reaction (ADR) occurrence and evaluation in elderly inpatients. Pharmacoepidemiol Drug Saf 5:9–18

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Caamano F, Pedone C, Zuccala G, Carbonin P (2005) Socio-demographic factors related to the prevalence of adverse drug reaction at hospital admission in an elderly population. Arch Gerontol Geriatr 40:45–52

    PubMed  Article  Google Scholar 

  3. 3.

    Camargo AL, Cardoso Ferreira MB, Heineck I (2006) Adverse drug reactions: a cohort study in internal medicine units at a university hospital. Eur J Clin Pharmacol 62:143–149

    PubMed  Article  Google Scholar 

  4. 4.

    Carbonin P, Pahor M, Bernabei R, Sgadari A (1991) Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 39:1093–1099

    PubMed  CAS  Google Scholar 

  5. 5.

    Gonzalez-Martin G, Yanez CG, Gonzalez-Contreras L, Labarca J (1999) Adverse drug reactions (ADRs) in patients with HIV infection, A prospective study. Int J Clin Pharmacol Ther 37:34–40

    PubMed  CAS  Google Scholar 

  6. 6.

    Hoigne R, Sollberger J, Zoppi M, Muller U, Hess T, Fritschy D, Stocker F, Maibach R (1984) [Significance of age, sex, kidney function, atopy and number of prescriptions for the occurrence of adverse drug reactions, studied by multivariate statistical methods. Results from the Comprehensive Hospital Drug Monitoring Berne (CHDMB)]. Schweiz Med Wochenschr 114:1854–1857

    PubMed  CAS  Google Scholar 

  7. 7.

    Light KP, Lovell AT, Butt H, Fauvel NJ, Holdcroft A (2006) Adverse effects of neuromuscular blocking agents based on yellow card reporting in the U.K.: are there differences between males and females? Pharmacoepidemiol Drug Saf 15:151–160

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Onder G, Pedone C, Landi F, Cesari M, Della Vedova C, Bernabei R, Gambassi G (2002) Adverse drug reactions as cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA). J Am Geriatr Soc 50:1962–1968

    PubMed  Article  Google Scholar 

  9. 9.

    Tran C, Knowles SR, Liu BA, Shear NH (1998) Gender differences in adverse drug reactions. J Clin Pharmacol 38:1003–1009

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    van den Bemt PM, Egberts AC, Lenderink AW, Verzijl JM, Simons KA, van der Pol WS, Leufkens HG (2000) Risk factors for the development of adverse drug events in hospitalized patients. Pharm World Sci 22:62–66

    PubMed  Article  Google Scholar 

  11. 11.

    Aros CA, Ardiles LG, Schneider HO, Flores CA, Alruiz PA, Jerez VR, Mezzano SA (2005) No gender-associated differences of cyclosporine pharmacokinetics in stable renal transplant patients treated with diltiazem. Transplant Proc 37:3364–3366

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Trifiro G, Calogero G, Ippolito FM, Cosentino M, Giuliani R, Conforti A, Venegoni M, Mazzaglia G, Caputi AP (2005) Adverse drug events in emergency department population: a prospective Italian study. Pharmacoepidemiol Drug Saf 14(5):333–340

    PubMed  Article  Google Scholar 

  13. 13.

    Schwartz JB (2003) The influence of sex on pharmacokinetics. Clin Pharmacokinet 42:107–121

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Kashuba AD, Nafziger AN (1998) Physiological changes during the menstrual cycle and their effects on the pharmacokinetics and pharmacodynamics of drugs. Clin Pharmacokinet 34:203–218

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Anderson GD (2005) Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 14:19–29

    Article  Google Scholar 

  16. 16.

    Tanaka E (1999) Gender-related differences in pharmacokinetics and their clinical significance. Clin Pharm Ther 24:339–346

    CAS  Google Scholar 

  17. 17.

    Zhu Y, Statkevich P, Curtis D, Cutler DL, Zhang M, Richards W (2004) Effects of age and gender on the pharmacokinetics of lonafarnib (L) following a single oral dose. Clin Pharm Ther 75:P59

    Google Scholar 

  18. 18.

    Dormann H (2006) Model-Projekt OntoDrug: Befundpräsentation Arzneimittelnebenwirkung DMW 34/35

  19. 19.

    WHO (2006) WHO Collaboration Centre for Drug Statistics Methodology. Guidelines for ATC classification 2006. Cited March 17, 2008.

  20. 20.

    Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–1259

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245

    PubMed  CAS  Google Scholar 

  22. 22.

    Dormann H, Muth-Selbach U, Krebs S, Criegee-Rieck M, Tageder I, Schneider HT, Hahn EG, Levy M, Brune K, Geisslinger G (2000) Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting. Drug Saf 22:161–168

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Uppsala Monitoring Centre (2008) The Uppsala Monitoring Centre. Causality Assessment of Suspected Adverse Reactions, 2008. Cited March 17, 2008.

  24. 24.

    WHO (2005) The WHO Adverse Reaction Terminology – WHO ART. Terminology for coding clinical information in relation to drug therapy, 2005. Cited March 17, 2008.

  25. 25.

    Gray SL, Mahoney JE, Blough DK (1999) Adverse drug events in elderly patients receiving home health services following hospital discharge. Ann Pharmacother 33:1147–1153

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Beierle I, Meibohm B, Derendorf H (1999) Gender differences in pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther 37:529–547

    PubMed  CAS  Google Scholar 

  27. 27.

    Franconi F, Brunelleschi S, Steardo L, Cuomo V (2007) Gender differences in drug responses. Pharmacol Res 55:81–95

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Kando JC, Yonkers KA, Cole JO (1995) Gender as a risk factor for adverse events to medications. Drugs 50:1–6

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Krecic-Shepard ME, Barnas CR, Slimko J, Jones MP, Schwartz JB (2000) Gender-specific effects on verapamil pharmacokinetics and pharmacodynamics in humans. J Clin Pharmacol 40:219–230

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Passarelli MC, Jacob-Filho W, Figueras A (2005) Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging 22:767–777

    PubMed  Article  Google Scholar 

  31. 31.

    Bates DW, Miller EB, Cullen DJ, Burdick L, Williams L, Laird N, Petersen LA, Small SD, Sweitzer BJ, Vander Vliet M, Leape LL (1999) Patient risk factors for adverse drug events in hospitalized patients ADE Prevention Study Group. Arch Intern Med 159:2553–2560

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Cosentino M, Leoni O, Banfi F, Lecchini S, Frigo G (1997) Attitudes to adverse drug reaction reporting by medical practitioners in a Northern Italian district. Pharmacol Res 35:85–88

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Gurwitz JH, Avorn J (1990) Old age–is it a risk for adverse drug reactions? Agents Actions (Suppl) 29:13–25

    CAS  Google Scholar 

  34. 34.

    Vakil BJ, Kulkarni RD, Chabria NL, Chadha DR, Deshpande VA (1975) Intense surveillance of adverse drug reactionsAn analysis of 338 patients. J Clin Pharmacol 15:435–441

    PubMed  CAS  Google Scholar 

  35. 35.

    Atkin PA, Veitch PC, Veitch EM, Ogle SJ (1999) The epidemiology of serious adverse drug reactions among the elderly. Drugs Aging 14:141–152

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Schwartz JB (2007) The current state of knowledge on age, sex, and their interaction on clinial pharmacology. Clin Pharmacol Ther 82:87–96

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Harris RZ, Benet LZ, Schwartz JB (1995) Gender effects in pharmacokinetics and pharmacodynamics. Drugs 50:222–239

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Hunt CM, Westerkam WR, Stave GM (1992) Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 44:275–283

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Rademaker M (2001) Do women have more adverse drug reactions? Am J Clin Dermatol 2:349–351

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Bebia Z, Buch SC, Wilson JW, Frye RF, Romkes M, Cecchetti A, Chaves-Gnecco D, Branch RA (2004) Bioequivalence revisited: influence of age and sex on CYP enzymes. Clin Pharmacol Ther 76:618–627

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Laine K, Tybring G, Bertilsson L (2000) No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Clin Pharmacol Ther 68:151–159

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Wilkinson GR, Guengerich FP, Branch RA (1989) Genetic polymorphism of S-mephenytoin hydroxylation. Pharmacol Ther 43:53–76

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Hagg S, Spigset O, Dahlqvist R (2001) Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Br J Clin Pharmacol 51:169–173

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Gleiter CH, Gundert-Remy U (1996) Gender differences in pharmacokinetics. Eur J Drug Metab Pharmacokinet 21:123–128

    PubMed  CAS  Google Scholar 

  45. 45.

    Drici MD, Clement N (2001) Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf 24:575–585

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Wolbrette DL (2003) Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. Am J Cardiol 91:39D–44D

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Wolbrette D (2002) Gender differences in the proarrhythmic potential of QT-prolonging drugs. Curr Womens Health Rep 2:105–109

    PubMed  Google Scholar 

  48. 48.

    Peters RW, Gold MR (2004) The influence of gender on arrhythmias. Cardiol Rev 12:97–105

    PubMed  Article  Google Scholar 

  49. 49.

    Galatti L, Giustini SE, Sessa A, Polimeni G, Salvo F, Spina E, Caputi AP (2005) Neuropsychiatric reactions to drugs: an analysis of spontaneous reports from general practitioners in Italy. Pharmacol Res 51:211–216

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Domecq C, Naranjo CA, Ruiz I, Busto U (1980) Sex-related variations in the frequency and characteristics of adverse drug reactions. Int J Clin Pharmacol Ther Toxicol 18:362–366

    PubMed  CAS  Google Scholar 

Download references


We thank Ulrich Rothe (head of pharmacy at the University of Regensburg) and Prof. Dr. Jürgen Schölmerich (director of the Medical Department I) of the University Hospital of Regensburg for the possibility of implementing KLASSE in their departments to establish computerised intensive drug surveillance studies. We also thank Prof. Micha Levy, the former incumbent of the Wilfred P. and Rose J. Cohen chair in Internal Medicine and the former Chairman of Medicine at Hadassah-Hebrew University School of Medicine for his cooperation in developing KLASSE and the early discussions on this topic and his comments. Furthermore, we thank Prof. Petra Thürmann (director of the Helios Research Center, director of the Philipp Klee Institute for Clinical Pharmacology, member of the German Drug Commission) for discussions and important comments. Finally, we thank our physicians and pharmacists who participated in intensive pharmacovigilance, namely, M. Reisig, PhD, M. Finkenzeller, PhD, S. Krebs, PhD and for medical informatics A. Ackermann, PhD and M. Criegee-Rieck, PhD, for developing and implementing KLASSE in clinical routine.

Author information



Corresponding author

Correspondence to Y. Zopf.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zopf, Y., Rabe, C., Neubert, A. et al. Women encounter ADRs more often than do men. Eur J Clin Pharmacol 64, 999 (2008).

Download citation


  • Gender
  • Risk factors
  • Adverse drug reaction
  • Pharmacokinetics