No retraction, correction or concern found when last checked on Nov 1, 2026.

Problems and Progress regarding Sex Bias and Omission in Neuroscience Research

Tyler R. Will, Stephanie B. Proaño, Anly M. Thomas and 8 more

eneuro · 2017 · CC BY-NC-SA

doi:10.1523/eneuro.0278-17.2017

Abstract

Neuroscience research has historically ignored female animals. This neglect comes in two general forms. The first is sex bias, defined as favoring one sex over another; in this case, male over female. The second is sex omission, which is the lack of reporting sex. The recognition of this phenomenon has generated fierce debate across the sciences. Here we test whether sex bias and omission are still present in the neuroscience literature, whether studies employing both males and females neglect sex as an experimental variable, and whether sex bias and omission differs between animal models and journals. To accomplish this, we analyzed the largest-ever number of neuroscience articles for sex bias and omission: 6636 articles using mice or rats in 6 journals published from 2010 to 2014. Sex omission is declining, as increasing numbers of articles report sex. Sex bias remains present, as increasing numbers of articles report the sole use of males. Articles using both males and females are also increasing, but few report assessing sex as an experimental variable. Sex bias and omission varies substantially by animal model and journal. These findings are essential for understanding the complex status of sex bias and omission in neuroscience research and may inform effective decisions regarding policy action.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 52

1.
Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies · 2014
No notice
2.
Beach FA (1950 ) The snark was a boojum. Am Psychol 115–124.
Not in our library10.1037/h0056510
3.
Becker JB, Arnold AP, Berkley KJ, Blaustein JD, Eckel LA, Hampson E, Herman JP, Marts S, Sadee W, Steiner M, Taylor J, Young E (2005 ) Strategies and methods for research on sex differences in brain and behavior. Endocrinology 146:1650–1673.
Not in our library10.1210/en.2004-1142
4.
Female rats are not more variable than male rats: a meta-analysis of neuroscience studies · 2016
No notice
5.
Beery AK, Zucker I (2011 ) Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35:565–572.
Not in our library10.1016/j.neubiorev.2010.07.002
6.
Berkley KJ (1992 ) Vive la différence! Trends Neurosci 15:331–332.
Not in our library10.1016/0166-2236(92)90048-d
7.
Blaustein JD (2012 ) Animals have a sex, and so should titles and methods sections of articles in Endocrinology. Endocrinology 153:2539–2540.
Not in our library10.1210/en.2012-1365
8.
Brenowitz EA, Zakon HH (2015 ) Emerging from the bottleneck: benefits of the comparative approach to modern neuroscience. Trends Neurosci 38:273–278.
Not in our library10.1016/j.tins.2015.02.008
9.
Brooks CE, Clayton JA (2017 ) Sex/gender influences on the nervous system: basic steps toward clinical progress. J Neurosci Res 95:14–16.
Not in our library10.1002/jnr.23902
10.
Cahill L, Aswad D (2015 ) Sex influences on the brain: an issue whose time has come. Neuron 88:1084–1085.
Not in our library10.1016/j.neuron.2015.11.021
11.
Clayton JA, Collins FS (2014 ) Policy: NIH to balance sex in cell and animal studies. Nature 509:282–283.
Not in our library10.1038/509282a
12.
Duchesne A, Tannenbaum C, Einstein G (2017 ) Funding agency mechanisms to increase sex and gender analysis. Lancet 389:699.
Not in our library10.1016/s0140-6736(17)30343-4
13.
Eliot L, Richardson SS (2016 ) Sex in context: limitations of animal studies for addressing human sex/gender neurobehavioral health disparities. J Neurosci 36:11823–11830.
Not in our library10.1523/jneurosci.1391-16.2016
14.
Fields RD (2014 ) NIH policy: mandate goes too far. Nature 510:340.
Not in our library10.1038/510340a
15.
Flórez-Vargas O, Brass A, Karystianis G, Bramhall M, Stevens R, Cruickshank S, Nenadic G (2016 ) Bias in the reporting of sex and age in biomedical research on mouse models. eLife 5:e13615.
Not in our library10.7554/elife.13615
16.
Freedman LP, Venugopalan G, Wisman R (2017 ) Reproducibility2020: progress and priorities. F1000Res 6:604.
Not in our library10.12688/f1000research.11334.1
17.
Guizzetti M, Davies DL, Egli M, Finn DA, Molina P, Regunathan S, Robinson DL, Sohrabji F (2016 ) Sex and the lab: an alcohol-focused commentary on the NIH initiative to balance sex in cell and animal studies. Alcohol Clin Exp Res 40:1182–1191.
Not in our library10.1111/acer.13072
18.
Han S, Olonisakin TF, Pribis JP, Zupetic J, Yoon JH, Holleran KM, Jeong K, Shaikh N, Rubio DM, Lee JS (2017 ) A checklist is associated with increased quality of reporting preclinical biomedical research: a systematic review. PLoS One 12:e0183591.
Not in our library10.1371/journal.pone.0183591
19.
Joel D, McCarthy MM (2017 ) Incorporating sex as a biological variable in neuropsychiatric research: where are we now and where should we be? Neuropsychopharmacology 42:379–385.
Not in our library10.1038/npp.2016.79
20.
Johnson J, Sharman Z, Vissandjée B, Stewart DE (2014 ) Does a change in health research funding policy related to the integration of sex and gender have an impact? PLoS One 9:e99900.
Not in our library10.1371/journal.pone.0099900
21.
Prevalence of sexual dimorphism in mammalian phenotypic traits · 2017
No notice
22.
Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research · 2010
No notice
23.
Klein SL, Schiebinger L, Stefanick ML, Cahill L, Danska J, de Vries GJ, Kibbe MR, McCarthy MM, Mogil JS, Woodruff TK, Zucker I (2015 ) Opinion: Sex inclusion in basic research drives discovery. Proc Natl Acad Sci U S A 112:5257–5258.
Not in our library10.1073/pnas.1502843112
24.
Krebs HA (1975 ) The August Krogh principle: “For many problems there is an animal on which it can be most conveniently studied.” J Exp Zool 194:221–226.
Not in our library10.1002/jez.1401940115
25.
Maney DL (2016 ) Perils and pitfalls of reporting sex differences. Philos Trans R Soc Lond B Biol Sci 371:20150119.
Not in our library10.1098/rstb.2015.0119
26.
McCarthy MM (2015 ) Incorporating sex as a variable in preclinical neuropsychiatric research. Schizophr Bull 41:1016–1020.
Not in our library10.1093/schbul/sbv077
27.
McCullough LD, McCarthy MM, de Vries GJ (2014 ) NIH policy: status quo is also costly. Nature 510:340.
Not in our library10.1038/510340b
28.
McEwen BS, Milner TA (2017 ) Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res 95:24–39.
Not in our library10.1002/jnr.23809
29.
McNutt M (2014 ) Journals unite for reproducibility. Science 346:679.
Not in our library10.1126/science.aaa1724
30.
Miller LR, Marks C, Becker JB, Hurn PD, Chen WJ, Woodruff T, McCarthy MM, Sohrabji F, Schiebinger L, Wetherington CL, Makris S, Arnold AP, Einstein G, Miller VM, Sandberg K, Maier S, Cornelison TL, Clayton JA (2017 ) Considering sex as a biological variable in preclinical research. FASEB J 31:29–34.
Not in our library10.1096/fj.201600781r
31.
Miller VM (2012 ) In pursuit of scientific excellence: sex matters. Am J Physiol Cell Physiol 302:C1269–C1270.
Not in our library10.1152/ajpcell.00073.2012
32.
Mogil JS (2016 ) Perspective: equality need not be painful. Nature 535:S7.
Not in our library10.1038/535s7a
33.
Mogil JS, Chanda ML (2005 ) The case for the inclusion of female subjects in basic science studies of pain. Pain 117:1–5.
Not in our library10.1016/j.pain.2005.06.020
34.
Moher D, Avey M, Antes G, Altman DG (2015 ) The National Institutes of Health and guidance for reporting preclinical research. BMC Med 13:34.
Not in our library10.1186/s12916-015-0284-9
35.
Guidance for Developers of Health Research Reporting Guidelines · 2010
No notice
36.
Nature (2014 ) Journals unite for reproducibility. Nature 515:7.
Not in our library10.1038/515007a
37.
Panzica G, Melcangi RC (2016 ) Structural and molecular brain sexual differences: a tool to understand sex differences in health and disease. Neurosci Biobehav Rev 67:2–8.
Not in our library10.1016/j.neubiorev.2016.04.017
38.
Park MN, Park JH, Paik HY, Lee SK (2015 ) Insufficient sex description of cells supplied by commercial vendors. Am J Physiol Cell Physiol 308:C578–C580.
Not in our library10.1152/ajpcell.00396.2014
39.
Remage-Healey L, Krentzel AA, Macedo-Lima M, Vahaba D (2017 ) Species diversity matters in biological research. Policy Insights Behav Brain Sci 4:210–218.
Not in our library10.1177/2372732217719908
40.
Richardson SS, Reiches M, Shattuck-Heidorn H, LaBonte ML, Consoli T (2015 ) Opinion: Focus on preclinical sex differences will not address women’s and men’s health disparities. Proc Natl Acad Sci U S A 112:13419–13420.
Not in our library10.1073/pnas.1516958112
41.
A meta-analysis of sex differences in human brain structure · 2014
No notice
42.
Sechzer JA, Rabinowitz VC, Denmark FL, McGinn MF, Weeks BM, Wilkens CL (1994 ) Sex and gender bias in animal research and in clinical studies of cancer, cardiovascular disease, and depression. Ann N Y Acad Sci 736:21–48.
Not in our library10.1111/j.1749-6632.1994.tb12816.x
43.
Sekula P, Mallett S, Altman DG, Sauerbrei W (2017 ) Did the reporting of prognostic studies of tumour markers improve since the introduction of REMARK guideline? A comparison of reporting in published articles. PLoS One 12:e0178531.
Not in our library10.1371/journal.pone.0178531
44.
Shansky RM, Woolley CS (2016 ) Considering sex as a biological variable will be valuable for neuroscience research. J Neurosci 36:11817–11822.
Not in our library10.1523/jneurosci.1390-16.2016
45.
Smidt N, Rutjes AW, van der Windt DA, Ostelo RW, Bossuyt PM, Reitsma JB, Bouter LM, de Vet HC (2006 ) The quality of diagnostic accuracy studies since the STARD statement: has it improved? Neurology 67:792–797.
Not in our library10.1212/01.wnl.0000238386.41398.30
46.
Tannenbaum C, Schwarz JM, Clayton JA, de Vries GJ, Sullivan C (2016 ) Evaluating sex as a biological variable in preclinical research: the devil in the details. Biol Sex Differ 7:13.
Not in our library10.1186/s13293-016-0066-x
47.
Taylor KE, Vallejo-Giraldo C, Schaible NS, Zakeri R, Miller VM (2011 ) Reporting of sex as a variable in cardiovascular studies using cultured cells. Biol Sex Differ 2:11.
Not in our library10.1186/2042-6410-2-11
48.
Thigpen JE, Setchell KD, Kissling GE, Locklear J, Caviness GF, Whiteside T, Belcher SM, Brown NM, Collins BJ, Lih FB, Tomer KB, Padilla-Banks E, Camacho L, Adsit FG, Grant M (2013 ) The estrogenic content of rodent diets, bedding, cages, and water bottles and its effect on bisphenol A studies. J Am Assoc Lab Anim Sci 52:130–141.
Not in our library
49.
Turner L, Shamseer L, Altman DG, Weeks L, Peters J, Kober T, Dias S, Schulz KF, Plint AC, Moher D (2012 ) Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals. Cochrane Database Syst Rev 11:MR000030.
Not in our library10.1002/14651858.mr000030.pub2
50.
Wizemann TM (2012 ). Sex-Specific Reporting of Scientific Research: A Workshop Summary. Washington, DC, National Academy of Sciences.
Not in our library
51.
Yoon DY, Mansukhani NA, Stubbs VC, Helenowski IB, Woodruff TK, Kibbe MR (2014 ) Sex bias exists in basic science and translational surgical research. Surgery 156:508–516.
Not in our library10.1016/j.surg.2014.07.001
52.
Zakiniaeiz Y, Cosgrove KP, Potenza MN, Mazure CM (2016 ) Balance of the sexes: addressing sex differences in preclinical research. Yale J Biol Med 89:255–259.
Not in our library

Cited by papers we hold 4

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.