Sex bias in neuroscience and biomedical research

Abstract

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.

Figure 1

Distribution of studies by sex and field in 2009. (A) Percent of articles describing non-human animal research that used male subjects, female subjects, both male and female subjects, or did not specify the sex of the subjects. (B) Percent of articles describing human research in the same categories. The zoology category was excluded because of insufficient use of human subjects in this field to form an accurate estimate.

Figure 2

Percent of articles in which some portion of the results was analyzed by sex. Data are presented by discipline for articles that utilized both sexes.

Figure 3

Species use in animal studies by subject area in 2009. Six fields (general biology, immunology, neuroscience, physiology, pharmacology, and endocrinology) relied on rodents in 80% or more of animal studies.

Figure 4

Historical change in study sex distribution in animal and human literatures. (A) Combined data from two journals publishing primarily non-human animal research: JPET and J Physiol.. Human studies were excluded from consideration for this graph. (B) Combined data from two clinical journals: JCEM and J Clin Invest. JCEM debuted in 1941. Animal studies were excluded from consideration for this graph. In the both animal and human literatures the number of studies in which sex is not specified has declined, but remains close to 20% in the animal literature. In the human literature there has been an increase in percent of studies of both sexes, not echoed in non-human animal research. Animal studies restricted to males alone have become more common in recent years.