Unmasking the Adverse Impacts of Sex Bias on Science and Research Animal Welfare

SIMPLE SUMMARY: Sex bias—the use of one sex over the other—is a common practice in biomedical research, typically with over selection of male animals. There are a number of reasons that this practice is common, but it has resulted in dosing errors and unintended side effects in a number of cases in women when products are given without adequate testing in female animals. Sex bias can also result in animal welfare issues given that both sexes are born in approximately equal numbers. Welfare issues include overproduction of the unwanted sex, inadequate ability to recognize and treat pain in female animals, stress associated with differential housing needs based on animal sex, and potential wastage of animals if study results are incorrect or studies need to be redone because only one sex was studied. Even though many government agencies and funding sources now require both sexes to be studied in biomedical research, single-sex studies are still common. More systematic planning and reporting of study details is needed, as well as exploring sex selection technology used in other animal production sectors when single-sex studies are justified, to reduce animal waste. ABSTRACT: Sex bias in biomedical and natural science research has been prevalent for decades. In many cases, the female estrous cycle was thought to be too complex an issue to model for, and it was thought to be simpler to only use males in studies. At times, particularly when studying efficacy and safety of new therapeutics, this sex bias has resulted in over- and under-medication with associated deleterious side effects in women. Many sex differences have been recognized that are unrelated to hormonal variation occurring during the estrous cycle. Sex bias also creates animal welfare challenges related to animal over-production and wastage, insufficient consideration of welfare (and scientific) impact related to differential housing of male vs female animals within research facilities, and a lack of understanding regarding differential requirements for pain recognition and alleviation in male versus female animals. Although many funding and government agencies require both sexes to be studied in biomedical research, many disparities remain in practice. This requires further enforcement of expectations by the Institutional Animal Care and Use Committee when reviewing protocols, research groups when writing grants, planning studies, and conducting research, and scientific journals and reviewers to ensure that sex bias policies are enforced.