Are hormones a ‘female problem’ for animal research?

Women, but not men, are often still described as “hormonal” or “emotional,” an outdated stereotype that poses a critical problem for public health, writes Rebecca Shansky in this Perspective. The belief that circulating ovarian hormones make data from female subjects “messier” continues to influence experimental design in laboratory animals today, with animals often still largely male, particularly in Shansky’s field of neuroscience. “When we view females through a male lens,” Shanksy says, “we risk missing what may be at the crux of the question for females,” an issue especially troublesome in behavior studies related to mood and anxiety disorders, like Major Depressive Disorder and Post-Traumatic Stress Disorder, both twice as prevalent in women. The idea that the estrous cycle would make data from female subjects more variable than that from males has seemed like such a reasonable assumption throughout history, Shanksy writes, that it wasn’t examined scientifically until 2014, when meta-analyses of published neuroscience articles that used mice as subjects showed that data collected from female mice – regardless of the estrous cycle – did not vary more than that from males. In fact, in some instances male mice in fact varied more than females. In particular, group-housed males, but not females, established a dominance hierarchy that saw dominant males exhibiting testosterone levels on average five times as high as subordinates. Only in 2016 did any funding agency in the United States require grant recipients to use both sexes in animal studies, with the introduction of the Sex as a Biological Variable (SABV) mandate. However, because the SABV mandate does not explicitly dictate how to incorporate both sexes into experimental designs, one “compromise” upon which some neuroscientists have landed is to work things out in males first, and then, armed with their findings, tackle the same question in females. This strategy is “dangerous,” Shansky says, “because it perpetuates the dated, sexist, and scientifically inaccurate idea that male brains are a standard from which female brains deviate. She says it is imperative that in adhering to the mandate, researchers do not allow antiquated gender stereotypes to bias their approach to scientific rigor. “Women are not more complicated than men, and hormones are not a ‘female problem’ for animal research. We need to stop treating them that way.”

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