Great piece Aarthi! Super appreciate the external link that you provided from Scientific American.

The issue you bring up is a general issue within a lot of scientific research right now. The NIH thankfully makes it a requirement now that you include both sexes in all preclinical studies. I am super intrigued by the point you brought  up with regards to the sex differences in neurological and psychiatric  conditions. It really seems that the sex differences in these conditions have been the main driving point to really start considering sex differences in other health conditions. I recently reviewed the literature with regards to the sexual dimorphism of the placenta, and many of the papers I came  upon had as their rationale the sex differences in neurological and psychiatric conditions in humans. It seems that even in the case of placental development and function, sex differences are KEY. The literature was supporting the idea that the placenta produces sexually dimorphic responses to intrauterine stress exposure which leads to differences in neurodevelopment in the fetus. And thus, possibly explaining the differences in disease prevalence. Thanks for this! 

Thanks for writing this piece. I think it is an extremely important point to  make not just to the neuroscience research community but to the general public. I was actually unaware that some researchers have equated sex differences in the brain as a form of ‘neurosexism’.  It’s an interesting argument because while as a woman in STEM I understand the need to combat sexism in the workplace, I also know that sex differences  do play an important role in many neurological diseases and neuropsychiatric conditions. For example, in pre-clinical stroke research there is a huge push to start incorporating male and female animals in studies in order to examine sex differences in post stroke recovery. This push is based on the fact that women over the age of 60 who have strokes are more likely to die or have worse functional  impairments compared to men over 60. These statistics clearly point to sex differences in brain responses to stroke, therefore validating the need to address sex differences in neuroscience research. 

As Laetitia said, the NIH has begun to address the issue of including male and female subjects in clinical studies due to clear differences in responses to drug treatments.

Basic science falls further behind in dealing with sex and gender differences. Female mice are traditionally excluded from behavioral research because people believed the estrous cycle might cause uncontrollable variability. This belief may be based on erroneous anecdotal evidence, and recent research shows that variability may even be higher for males.

Classic work in pain processing performed in male mice has turned out to only apply to males. By excluding females, we fail to recognize possible sex differences in unexpected places that may also extend to humans.

Clear sex-specific differences in responses to drug treatments have fueled a response to the problem of focusing on men for research studies. However, ignoring the problem at the basic science level creates a dangerous situation in which a lack of knowledge can perpetuate misunderstandings about how the female nervous system works.

Thanks for this great article on a major social issue that impacts neuroscience and biology research every day.

Great piece Aarthi!

I was particularly interested in the part where you mention how results from studies investigating sex differences in the brain might have implications in academic institutions! This is definitely something that is worth pondering over. My concern is that these might not only have implications in academia but in society as a whole. For instance, how will this influence the pay gap? How will this translate in courtrooms? Are women more or less accountable for a crime because of the effects of female hormones on emotions and behaviour? Research involving female and male participants will definitely move the field of neuroscience forward in many ways but we must acknowledge that it might also carry several implications on gender inequality.

Thanks so much everyone for the supportive words! I wanted to share my thoughts to some of the thoughtful points raised here:

I love the point raised by Jenna about sex differences in pain responses. Stories from women experiencing distress and poor medical treatment because their doctors dismissed their pain or did not treat the pain as serious red flags of underlying physiological problems are gaining more visibility. But, if we believe women’s pain only to treat them with drugs that were optimized for the male nervous system, then we are still failing to provide good medical treatment for female patients. Addressing sex and gender differences is important for preclinical and clinical perspectives.

And thank you for bringing up that point about the estrous cycle–the estrous cycle does not make data more variable! I get frustrated when I hear scientists try to justify excluding females for that reason because it seems rooted in a misogynistic belief that hormones make females problematic–even though everyone has hormones! Conflating hormone cycles with unpredictability or treating them as a frivolous complication seems like a way to undermine women, both in data sets and in real life.

I also agree with the point raised by Katherine - I think the implications of sex differences in the brain have broad impacts well outside academia, and I’m fascinated by how neuroscience in general will intersect with the law. As the field of neuroethics grows, I hope it paves the way for better communication between researchers and public audiences.

Love this piece. An article recently came out in Science directly discussing this topic. My biggest takeaway from this article was the general bias against female mice for “hormonal problems” that could make their behavior too erratic for study. This bias can be dangerous, as scientific results that lead to drug or treatment development are inherently skewed to favor men (as discussed in the article). However, a metadata analysis of almost 300 different articles shows the opposite: females are not significantly more variable than males in various behavioral, physiological, and morphological traits.

It is important to remember that these biases stem from trends in the basic research and the structure of the research experiments themselves. Male mice are preferentially used in basic science experiments. This trend has been present in neuroscience research since the 1950s, and many landmark findings were made exclusively in male models (i.e. aspirin). In 2016, the NIH and CIHR both required science produced under their grants to consider sex as a biological variable for reporting, which has remained controversial.

Not only do we need to focus on the using the results of sex differences in the brain for treatment more seriously, but there also needs to be a serious overhaul in the current basic experimental procedure to even create more female-oriented data!

Wonderful piece! I was just thinking/hoping to see a piece about sex differences in the brain as the FDA just approved it’s first drug for post partum depression recently from Sage Therapeutics. As great as this breakthrough is, it really highlights how behind we are; that in 2019, the first treatment for a disorder affecting 15% of births is only just now being approved.

Additionally, sex differences in alcohol drinking in females is widely reported in the alcohol field and recent research shows increases in binge drinking in women (Breslow, Castle, Chen, & Graubard, 2017) further highlighting the need to include females in basic animal research on alcohol drinking to better understand how alcohol affects females as well.

Also, snaps to Jenna for bringing up the excuse of many researchers to exclude female mice from their research because of their estrous cycle as if males do not also have sex hormones!

Great piece Aarthi Thank you for bringing up the social impact neuroscience research has on marginalized groups as well. It makes platforms like this all the more important for scientists to be able to communicate their science accurately and easily to avoid data being used in the wrong way.

Thank you for writing this piece Aarthi. Avoiding the use of women and female animals in research because of their “complicated hormones” has been a long-time problem in neuroscience and other areas of psychology. Whether it is true that females are “harder to study” because their hormones are more variable (and some research shows that this belief is not based on empirical evidence), this is nevertheless a limitation that researchers will have to address and fix to produce good science. Thankfully, newer research is challenging assumptions about how hard it is to statistically control for the female menstrual cycle, and there is a greater push for neuroscientists to use both male and female rats in their studies.

On the flip side, I can see why scientists like Gina Rippon and others are worried about neurosexism. Often, sex differences in studies are small to moderate and yet they are exaggerated in the media, leading the lay public to speculate about what this means in terms of differences between men and women and their respective values to society. Are they just differences or are they hierarchical? This is why it is important to point out the effect sizes, or magnitude of differences, in studies of sex differences, as opposed to simply stating whether a difference was detected.

It also seems to me that Rippon and others of the same mindset don’t necessarily believe that men and women’s brains are exactly identical either but that they are 1) plastic, and 2) where there are differences, they develop by way of gendered socialization. This view, while not entirely wrong, does deserve some criticism (i.e., nature and nurture are inextricably linked, after all, and downplaying the nature side of things does nothing to further scientific knowledge or help with gender inequality).

At any rate, it is important that science communicators continue to set the record straight that biology is not destiny (ostensibly a more widely held belief than the environment-is-destiny view) and that pointing out that there are sex differences in the brain says nothing about whether those differences are immutable, how they developed (and everything must develop somehow, whether in or outside the womb), or whether they mean that one group is inherently “better” than the other. If and how long it will take for these messages to get through to lay audiences, however, remains to be seen.