Evidence map›Paper›PMID 36307876›Full record

ArticleBiology of sex differences2022

Why the estrous cycle matters for neuroscience.

Devin Rocks, Heining Cham, Marija Kundakovic

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
18.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 100 citations in OpenAlex.

  1. Article
  2. Nucleus accumbens neuron subtype translatome signatures in socially stressed females.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  8. Review
  9. Review
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  12. Single-cell map of the female brain across reproductive transitions.bioRxiv : the preprint server for biology · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Devin RocksDepartment of Biological Sciences, Fordham University, 441 E. Fordham Road, Larkin Hall 160, Bronx, NY, 10458, USA.
Heining ChamDepartment of Psychology, Fordham University, 441 E. Fordham Road, Dealy Hall 226G, Bronx, NY, 10458, USA.
Marija KundakovicDepartment of Biological Sciences, Fordham University, 441 E. Fordham Road, Larkin Hall 160, Bronx, NY, 10458, USA. mkundakovic@fordham.edu.ORCID 0000-0002-6734-4217
Fordham University · US

Funding

Epigenetic regulation of brain and behavior by the estrous cycleR01MH123523 · NIMH · FORDHAM UNIVERSITY · PI KUNDAKOVIC, MARIJA · 2021 to 2025
$1.9M
NIMH NIH HHS R01 MH123523
6 · The paper itself

Abstract

backgroundOvarian hormone fluctuations over the rodent estrous cycle and the human menstrual cycle are known to significantly impact brain physiology and disease risk, yet this variable is largely ignored in preclinical neuroscience research, clinical studies, and psychiatric practice.

methodsTo assess the importance of the estrous cycle information for the analysis of sex differences in neuroscience research, we re-analyzed our previously published data with or without the estrous cycle information, giving a side-by-side comparison of the analyses of behavior, brain structure, gene expression, and 3D genome organization in female and male mice. We also examined and compared the variance of female and male groups across all neurobehavioral measures.

resultsWe show that accounting for the estrous cycle significantly increases the resolution of the neuroscience studies and allows for: (a) identification of masked sex differences; (b) mechanistic insight(s) into the identified sex differences, across different neurobehavioral outcomes, from behavior to molecular phenotypes. We confirm previous findings that female data from either mixed- or staged-female groups are, on average, not more variable than that of males. However, we show that female variability is not, at all, predictive of whether the estrous cycle plays an important role in regulating the outcome of interest.

conclusionsWe argue that "bringing back" the estrous cycle variable to the main stage is important in order to enhance the resolution and quality of the data, to advance the health of women and other menstruators, and to make research more gender-inclusive. We strongly encourage the neuroscience community to incorporate the estrous cycle information in their study design and data analysis, whenever possible, and we debunk some myths that tend to de-emphasize the importance and discourage the inclusion of this critically important biological variable. Highlights Ovarian hormone fluctuation impacts brain physiology and is a major psychiatric risk factor, yet this variable has been overlooked in neuroscience research and psychiatric practice. From rodent behavior to gene regulation, accounting for the estrous cycle increases the resolution of the neuroscience data, allowing identification and mechanistic insight(s) into sex differences. Female variability does not equal (and is not predictive of) the estrous cycle effect and should not be used as a proxy for the effects of ovarian hormones on the outcome of interest. Neuroscience researchers are advised to incorporate the estrous cycle information in their studies to foster more equitable, female- and gender-inclusive research. Studies of the ovarian cycle are especially important for improving women's mental health.

Indexed as

Estrous CycleSex CharacteristicsAnimalsFemaleHormonesHumansMaleMenstrual CycleMiceHormones

Identifiers

PMID36307876
PMCPMC9615204
OpenAlexW4308254599

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.