Sex bias in neuroscience and biomedical research
Open accessAbstract
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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Women were historically excluded from research partly because ovarian hormone fluctuations were assumed to induce variability, especially in emotion, that could not be experimentally controlled.
“Women were historically excluded from research participation partly due to the assumption that ovarian hormone fluctuations lead to variation, especially in emotion, that could not be experimentally controlled.”
From Little evidence for sex or ovarian hormone influences on affective variability (2021) · cites this paper as [1]
The Introduction says women and female mammals were underrepresented partly because hormonal cycles were thought to reduce study-population homogeneity and confound experiments; the Conclusions describe perceived complications from ovarian hormone variation. The paper does not identify emotion as an especially variable outcome, and its Recommendations say hormone variation can be incorporated into study design, rather than establishing that it could not be experimentally controlled. The supplied passages have section labels but no page numbers. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTo avoid confounding effects of fluctuating ovarian hormones in females, only male mice were used.
“To avoid the confounding effects of fluctuating ovarian hormones in females (Beery and Zucker, 2011), nine male 3×Tg-AD mice on a C57BL/6J-congenic background (approximately 7 months old) and nine control mice weighing approximately 25 to 30 g were procured from Wuhan Youdu Biotechnology Company (Wuhan, China; license no. SCXK (E) 2021-0025).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Beery and Zucker, 2011
The Introduction describes concern that hormonal cycles can confound experiments, so the cited paper supports the existence of that concern. But the Recommendations say female rodents can be studied without estrous-cycle confounding through appropriate study design; the paper does not support using males only as a necessary way to avoid it. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPrevious oxytocin studies are male biased and often constrained by task-based inferences.
“Previous oxytocin studies are male biased and often constrained by task-based inferences.”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [10]
There are notable male biases throughout neuroscience and medical research.
“There are notable male biases throughout neuroscience and medical research and this bias may explain why studies looking at the effects of drugs tend to miss many adverse effects or show a lack of efficacy when applied to females.10, 46”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [10]
This male bias may explain why studies looking at effects of drugs tend to miss many adverse effects or show a lack of efficacy when applied to females.
“There are notable male biases throughout neuroscience and medical research and this bias may explain why studies looking at the effects of drugs tend to miss many adverse effects or show a lack of efficacy when applied to females.10, 46”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [10]
Male bias is evident in most fields of biological research, and particularly so in the field of neuroscience, where males outnumber females at a ratio of 5.5 to 1.
“Male bias is evident in most fields of biological research, and particularly so in the field of neuroscience, where males outnumber females at a ratio of 5.5 to 1 [186].”
From Temperature regulation in women: Effects of the menstrual cycle (2020) · cites this paper as [186]
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- Authors
- Beery, A. K., & Zucker, I.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Corresponding author
- Zucker, Irving
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 35
- Issue
- 3
- Pages
- 565-572
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC3008499
- OpenAlex
- W2009792683
- Cited by
- 1,763
- References
- 67
- Citations by year
- 2026: 146 · 2025: 170 · 2024: 167 · 2023: 182 · 2022: 171 · 2021: 160 · 2020: 164 · 2019: 113 · 2018: 91 · 2017: 93 · 2016: 99 · 2015: 56 · 2014: 58 · 2013: 23 · 2012: 37
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Smith ScholarWorks (Smith College) (submittedVersion)
- Funders
- Robert Wood Johnson Foundation Health & Society Scholars program
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Social Sciences › Gender Studies › Diversity and Career in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- sex bias, sex differences in research, sex-inclusive research, sex as a biological variable, animal models of disease, rats and mice, brain research, biomedical research funding
- MeSH terms
- Animals, Female, Humans, Male, Neurosciences, Prejudice, Biomedical Research, Mice, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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