Various Aspects of Sex and Gender Bias in Biomedical Research

Abstract

The main role of research in medicine is to provide relevant knowledge which, after successful translation to clinical practice, improves the quality of healthcare. The sex bias which is still present in the majority of research disciplines prefers male subjects despite legislation changes in the US grant agencies and European research programme Horizon 2020. Male subjects (cells, animals) still dominate in preclinical research and it has detrimental consequences for women’s health and the quality of science. Opposite bias exists for data obtained mainly in animal models utilizing female subjects (e.g. research in multiple sclerosis, osteoporosis) with skewed outcomes for men affected by these diseases. Either way, scientists are producing results which compromise half of the population. Assumptions that females as cohorts are more variable and another assumption that the oestrous cycle should be tracked in case the females are enrolled in preclinical studies were proven wrong. Variability of male versus female cohorts are comparable and do not only stem from hormonal levels. The widespread prevalence of sex differences in human diseases ultimately requires detailed experiments performed on both sexes, unless the studies are specifically addressing reproduction or sex-related behaviors.

Effects of Oral 5-Aminolevulinic Acid on Lipopolysaccharide-Induced Ocular Inflammation in Rats

“…By synthesizing various cytokines and other inflammatory mediators, macrophages/monocytes may play an important role in EIU [ 38 ]. Macrophages and monocytes, followed by polymorphonuclear leukocytes and T cells, are the first inflammatory cells to enter the eye after LPS injection [ 39 ]. Thus, we used RAW264.7 cells to investigate the in vitro anti-inflammatory effects of 5-ALA. We found that 5-ALA significantly inhibited iNOS and tended to suppress COX-2 expression.…”

Cortical Spheroid Model for Studying the Effects of Ischemic Brain Injury

“…Males are over-represented in both in vitro and in vivo preclinical trials, and the use of male animals is about five-fold higher in both cardiovascular and neuroscience studies [26][27][28]. Many researchers do not know or do not report the sex of their cell sources, and although some steps have been taken to improve the representation of female animals in preclinical research there is still much room for improvement [26,29]. Progress in this area is particularly important as outcomes of neurological disorders involving ischemia, such as stroke, and drug interaction are sexually dimorphic [26,30].…”

Cortical Spheroid Model for Studying the Effects of Ischemic Brain Injury

“…Despite these sex differences, males are massively overrepresented in both in vitro and in vivo preclinical trials, and many researchers do not know or do not report the sex of their cell sources (Karp and Reavey 2019). The use of male animals is about five-fold higher in both cardiovascular and neuroscience studies, and although some steps have been taken to improve the representation of female animals in preclinical research there is still huge room for improvement (Ramirez et al 2017; Beery and Zucker 2011; Plevkova et al 2021). There is a need to study ischemic brain injury and test potential stroke therapeutics in both female and male derived in vitro models, as both stroke outcome and drug interaction are sexually dimorphic (Virani et al 2020; Karp and Reavey 2019).…”