Limits of mice and men: Underrepresenting female and intersex patients in anaesthesia research

Abstract

Abstract Animal model research is insufficient to guide the application of novel therapies in human patients, but the same objections should apply to human trials which do not representatively sample sexes in the population. Female participants have historically been excluded from anaesthesia research due to concerns of potential teratogenicity and unfounded apprehension that female hormones would interfere with the physiologic processes under examination. Consequently, many drugs currently available on the international market have not been thoroughly tested in female patients. The representation of intersex individuals in anaesthesia research, moreover, is exceedingly rare. An increasing awareness of these disparities in recent decades has led to the recognition of biological sex as an important pharmacodynamic variable, and the prospect that clinical decision-making in anaesthesia can be informed by known sex differences in the sensitivity to anaesthetics, the risk of adverse drug reactions, and the distribution and excretion of agents used to induce and maintain anaesthesia. Despite this, sex representation in anaesthesia research remains poorly regulated and sex-specific data are often reported in aggregate. Greater formal recognition of sex differences in study protocols and practice guidelines is warranted to meaningfully and incrementally improve anaesthesia care for female and intersex patients.