Sex-Related Differences in Drugs with Anti-Inflammatory Properties

Abstract

There is increasing evidence of sex differences in the action of anti-inflammatory drugs, with women being at significantly higher risk of adverse effects. Nevertheless, clinicians' awareness of the implications of these sex differences on dosing and adverse event monitoring in routine practice is still in need of improvement. We reviewed the literature evaluating sex differences in terms of pharmacokinetics and pharmacodynamics of anti-inflammatory drugs. The anti-thrombotic activity of selective and non-selective COX-inhibitors tends to be stronger in men than women. Side effect profiles differ with regards to gastro-intestinal, renal and hepatic complications. Glucocorticosteroids were found to be more effective in men; women were more sensitive to corticosteroids when their oestradiol levels were high, a finding important for women taking hormonal contraception. TNF-alpha inhibitors have a longer half-life in men, leading to stronger immunosuppression and this a higher incidence of infections as side effects. Although research on sex differences in the effectiveness and safety of drugs is increasing, findings are often anecdotal and controversial. There is no systematic sex-differentiated reporting from clinical trials, and women are often under-represented. As personalized medicine is gaining in importance, sex, and gender aspects need to become integral parts of future research and policy making.

Keywords: COVID-19; NSAID; SARS-CoV-2; anti-inflammatory drug; gender; pharmacodynamics; pharmacokinetics; sex; steroid.

Figure 1

Gender-specific differences in immune responses and inflammatory diseases. Multiple immunological factors vary between the sexes throughout the course of life. For certain factors (for example, pro-inflammatory responses), the sex differences change at puberty and then wane in later life, suggesting hormonal effects. For other factors, the sex difference remains constant from birth to old age (for example, higher numbers of CD4⁺ T cells and CD4/CD8 T cell ratios in females). The paucity of studies in this area is notable, particularly in utero sex differences in which results are conflicting. IL-10, interleukin-10; NK, natural killer; T_reg, regulatory T. Reproduced with permission from [26].