Sex and gender aspects in drug utilization

Drug prescribing is one of the most important processes in healthcare and drugs are also commonly used in the population. Drug use differs between men and women and descriptive reports of sex differences in drug use have been published with examples from different therapeutic areas. However, it’s not easy to gain a comprehensive overview as results differs, not only between therapeutic areas but also over time and between different populations. Differences between men and women are mostly caused by a combination of biological (sex) and socio-cultural (gender) factors. For example, there are differences between men and women in disease prevalence and comorbidity, pharmacokinetics and pharmacodynamics, and hormone levels as well as in perceptions of disease, help-seeking behavior, interaction with healthcare professionals and utilization of healthcare that may affect drug utilization.

Study I was an observational cross-sectional study using data from the Swedish Prescribed Drug Register (SPDR) analyzing differences between men and women in drug utilization, overall and within different pharmacological groups in Sweden 2010. Substantial sex differences in prevalence and incidence of dispensed drugs were found, for example in antibiotics and in cardiovascular drugs. Most differences were rational and reflected differences between men and women in the incidence or prevalence of disease or biological differences. Other differences were more difficult to explain on medical grounds and may indicate unequal treatment.

Study II was an observational cross-sectional study using data from the SPDR and The Swedish Drug Information System (SWEDIS) analyzing differences between men and women in bleeding event reports for clopidogrel, low-dose acetylsalicylic acid (Aspirin) and warfarin. Total number of bleeding event report for each substance was adjusted for dispensed drugs of that substance during the same time-period. For low-dose aspirin, there were significant sex differences with more bleeding event reports in men, regardless of whether the figures were adjusted for dispensed prescriptions or exposed individuals. For clopidogrel, bleeding event reports seemed to be more common in women when adjusting for exposed individuals, however the sex difference was not significant. For warfarin, bleeding event reports were more common in women when adjusting for dispensed prescriptions for the time-period 1999-2010, but otherwise no sex differences were found.

Study III was a qualitative study using focus groups discussions to explore general practitioners’ (GPs’) awareness of sex and gender differences and assess their perceptions of whether men and women are treated differently in primary care with a particular focus on medical treatment. Stereotyped perceptions of men and women existed among the physicians, but individual factors seemed to be taken into account more often than the patient’s sex when deciding on treatment. The physicians described that they followed the recommendations from the respective Drug and Therapeutics Committee (DTC), and that they relied on the DTCs’ to have considered sex and gender when making recommendations. The physicians expressed that they had no or very little knowledge of sex differences in drug treatment. However, they gave several examples of how they considered the patient’s sex in drug treatment indicating the opposite.

Study IV was a repeated observational cross-sectional study of individuals in the region of Stockholm with a diagnosis of nonvalvular atrial fibrillation in 2011 and 2015, respectively. Dispensed thromboprophylactic treatment, i.e. warfarin, non-vitamin K antagonist oral anticoagulants (NOACs), and low-dose aspirin, was described by sex and age group, and by sex and CHA2DS2-VASc score. The prevalence of atrial fibrillation increased in both men and women between 2011 and 2015, as did the proportion of patients using oral anticoagulants (OACs). Patients with comorbidities potentially complicating OAC use, such as prior severe bleed, anemia, dementia, alcoholism, and frequent falls, used more OAC in 2015 compared to 2011. OAC treatment was less common in women in 2011, however in 2015 the sex difference had disappeared, except in elderly and in patients with complicated comorbidity.

Study V was an observational study following a cohort of patients with epilepsy after stroke treated with antiepileptic drugs (AEDs) using data from a regional healthcare database on diagnoses and dispensed prescription drugs in Stockholm. Choice of AED when initiating treatment in men and women was described. Levetiracetam was most common in both men and women. Multinomial logistic regression identified several factors associated with choice of AED, including for instance patient sex, age, and renal impairment. Furthermore, persistence to therapy was studied for the most used AEDs and levetiracetam had the highest persistence in both men and women. Factors associated with AED discontinuation within 90-days were choice of AED, use of OAC and percutaneous endoscopic gastrostomy tube delivery of the drug (PEG).

List of scientific papers

I. Loikas D, Wettermark B, von Euler M, Bergman U, Schenck-Gustafsson K. Differences in drug utilisation between men and women: a cross-sectional analysis of all dispensed drugs in Sweden. BMJ Open. 2013;3(5).
https://doi.org/10.1136/bmjopen-2012-002378

II. Rydberg DM, Holm L, Mejyr S, Loikas D, Schenck-Gustafsson K, von Euler M, Wettermark B, Malmström RE. Sex differences in spontaneous reports on adverse bleeding events of antithrombotic treatment. Eur J Clin Pharmacol. 2014;70(1):117-26.
https://doi.org/10.1007/s00228-013-1591-8

III. Loikas D, Karlsson L, von Euler M, Hallgren K, Schenck-Gustafsson K, Bastholm Rahmner P. Does patient’s sex influence treatment in primary care? Experiences and expressed knowledge among physicians--a qualitative study. BMC Fam Pract. 2015;16:137.
https://doi.org/10.1186/s12875-015-0351-5

IV. Loikas D, Forslund T, Wettermark B, Schenck-Gustafsson K, Hjemdahl P, von Euler M. Sex and gender differences in thromboprophylactic treatment of patients with atrial fibrillation after the Introduction of non-vitamin K oral anticoagulants. Am J Cardiol. 2017;120(8):1302-8.
https://doi.org/10.1016/j.amjcard.2017.07.002

V. Loikas D, Linnér L, Sundström A, Wettermark B, von Euler M. Post-stroke epilepsy and antiepileptic drug use in men and women. [Submitted]