Sex bias in neuroscience and biomedical research

Robert Wood Johnson Health & Society Scholar at University of California, San Francisco, CA, USA.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 01/2011; 35(3):565-72. DOI: 10.1016/j.neubiorev.2010.07.002
Source: PubMed


Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex.

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    • "The resulting gender bias in animal research is a serious concern. Researchers are encouraged to study both males and females of each animal model [153]. In many studies significant gender differences are reported [154], but these are not taken into consideration in the design of subsequent clinical trials [155]. "
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    • "Moreover, the male GR DBHCre mutants not only did not exhibit changes in basal behavior but were resistant to chronic restraint stress, which clearly indicates the gender-dependent response to this particular mutation. The gender differences in our model are particularly interesting because depression is more prevalent in women (Seedat et al., 2009), and this issue has not been properly addressed in most descriptions of transgenic and pharmacological models of this illness (Beery and Zucker, 2011; Kreiner et al., 2013). Interestingly, several studies performed with transgenic mouse models with differences in male and female behavioral responses have reported gender-specific differences in depressive-like behavior after modification of the serotonergic system (Bhatnagar et al., 2004; Jones and Lucki, 2005), HPA axis elements (Chen et al., 2006; Solomon et al., 2012) and BDNF expression (Monteggia et al., 2007). "
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    • "However, in studies that employ animal models of depression and anxiety, there exists a large male bias, again due to the hormonal fluctuations at play during the estrous cycle which cause significant changes in both physiology and behaviour (for review see [45]. Zucker and Beery [5] [69] found that even in studies of diseases that predominantly affect women such as anxiety and depression, the research is primarily carried out with male animals. The environment can also play a large role in the development of depression. "
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