Gender differences in adverse drug reaction reports; How can they be explained?

Background/Introduction: In general, women have a higher risk for adverse drug reactions (ADRs) being reported than men [1]. Women also generally use more drugs as compared to men in various therapeutic areas [2]. It is unclear which differences in reporting pattern for both genders exist after correcting for drug use. Knowledge of these differences, and possible mechanisms that may explain them, may help in optimizing gender-specific pharmacotherapy. Objective/Aim: To assess and characterize gender differences in reported drug-ADR combinations to the national pharmacovigilance centre in the Netherlands, corrected for differences in drug use. Methods: We included drug-ADR combinations reported by healthcare professionals and patients to the Netherlands Pharmacovigilance Centre Lareb. Only combinations (ATC-MedDRA preferred term) that were reported at least 10 times between 2003 and 2016 for drugs that were used by ≥ 10,000 persons in that period were taken into account. Genderspecific ADRs, like gynaecological problems, were excluded. Data from the National Health Care Institute were used to correct for the number of users per drug. Gender differences in specific drug-ADR combinations were tested using bivariate logistic regression analyses, adjusted for the number of drug users per gender. Results: A total number of 2482 drug-ADR combinations were analysed. Statistically significant differences (p <0.05) were shown in 363 combinations (15%). Most of these drug-ADR combinations were reported more often for women (321 combinations, 88%). Drugs with the highest number of ADRs that were more often reported for women included thyroid hormones, and antidepressants. Some ADRs were predominantly reported for women across a range of drugs like headache and dizziness whereas other ADRs like tendon ruptures and aggression were reported more often for men. Conclusion: Identified gender differences in reporting ADRs often referred to women. These differences may have various causes. Men and women differ in respect to their physiology, immunological processes and type and function of various hormones. This may result in differences in pharmacokinetics and pharmacodynamics. Examples are the predominance of dose depending ADRs being reported in women which may depend on pharmacokinetic properties and the predominance of ADRs associated with psychotropic drugs which may be caused by differences in pharmacodynamics. Gender differences may also result of variations in perception by reporter and patient since they are experienced as bothersome depending on a gender-specific self-image. An example is the occurrence of hair thinning and hair loss, which is more common in aging men but is likely to be considered as disturbing particularly when it occurs in women. In addition, differences in background incidence in disorders and diseases between both genders exist and may be reflected in reporting ADRs. Finally, gender differences in reporting may result from variations in reporting behaviour of the reporter, either healthcare professional or patient. Further studies are needed to assess underlying reasons, including pharmacological and behavioural factors. The results may ultimately lead to gender-specific prescribing or monitoring recommendations