Including Female Subjects in Research

Whether you're studying humans, non-human primates, rodents, or even fish, it's important to consider including female subjects in your research. There are endless discoveries to be made about the brain, but when you exclude females you miss out on some of these opportunities. Here, I'll explain some of the key reasons why females need to be included in research, but it's important to note that there are many more reasons out there.

 

1) If you don't include females, we may never learn about important sex differences. Many recent studies have found that there are sex differences in areas we previously though to be similar between females and males. One example is traumatic brain injuries. In medicine, female subjects are often treated as though they're just smaller, strange males. Thinking like this have caused human women to go under diagnosed, suffer increased adverse drug reactions, and being overmedicated.

​

2) Females behave differently than males in a lot of tasks. Many studies have found that female subjects often perform differently than males and even when they perform similarly they may be using a different strategy. So making the assumption that females are just smaller males means you would miss out on the nuances of their behaviors. Not to mention that females and males respond differently to certain stimuli, like stress, so if you made a statement like "rats respond to stress by ___" without taking females into account, you would likely be incorrect. Assuming that females will behave the same as males has led people to use incorrect behavioral assays on females, like the elevated plus maze or open field test.

​

3) Only examining males perpetuates the harmful ideas that females don't belong in research, females are "too hormonal", and that males are normal while females are weird. It may seem like a small thing, but thinking like this leads to discrimination against women in medicine and in neuroscience. Both females and males of all species have hormonal cycles, whether that's an estrogen, progesterone, testosterone, or sleep cycle. Our bodies run on hormones and if all of your hormones were constantly the same, that would not be good. Sex differences are important to study, but they don't mean that any sex is better or worse than another. Studies in both rats and mice (two common research models) have shown that not only are females no more variable than males, but that including females in different stages of their hormonal cycle produces less variability than things like group versus single housing. 

​

4) Females are still understudied in neuroscience research. Which selfishly means that there is much more potential for you to discover something new by including females in your research!

​

But Morgan, I thought the NIH fixed this underrepresentation issue by requiring people to include both sexes in their research? In 2010 a study was published examining sex bias in neuroscience research. This study found that in non-human research for every paper published using females, 5.5 using males were published, showing a clear bias toward only studying males. Papers that included justification for only using males perpetuated the myth that females are inherently more variable than males. To attempt to address this issue, the NIH implemented a new policy that required researchers to consider sex as a biological variable. This sparked a follow up study in 2019 to examine the effectiveness of this new policy. This study found that, in the field of neuroscience, there was an increase from 29% of studies including females in 2009 to 63% in 2019! So problem solved, right? The study also found that only 42% of studies including both sexes analyzed their data including sex as a biological variable, meaning that 58% of studies *potentially* missed out on discovering new and exciting sex differences or varifying that females and males are similar in a particular aspect. Lasty, similarly to the previous study, they found that papers that justified their lack of female inclusion cited myths about increased variability in females. While it's great that neuroscience has made great strides in our inclusion of female subjects, we still have a long way to go and it is important that we continue advocating for the inclusion of both females and males in research.

​

Other useful resources:

Gender bias in (neuro)science: Facts, consequences, and solutions

Are hormones a "female problem" for animal research?

Strategies and methods for research on sex differences in brain and behavior

Inclusion of females does not increase variability in rodent research studies

Why neuroscience needs girls: gender diversity drives scientific discovery

Women in neuroscience: a short time travel

Considering sex as a biological variable will require a global shift in science culture

The perils and pitfalls of reporting sex differences

Reporting and mis-reporting of sex differences in the biological sciences