Evidence map›Paper›PMID 33704446›Full record

ArticleEndocrine reviews2021

Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement.

Aditi Bhargava, Arthur P Arnold, Debra A Bangasser, Kate M Denton, Arpana Gupta, Lucinda M Hilliard Krause, Emeran A Mayer, Margaret McCarthy, Walter L Miller, Armin Raznahan and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

69 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Biomaterials Empowering in New Era of Women's Healthcare System.Reproductive sciences (Thousand Oaks, Calif.) · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Toward Sex-Specific Biomaterials Innovation: A Perspective.ACS biomaterials science & engineering · 2025
    Review
  17. Article
  18. Article
  19. Longitudinal Sex-at-Birth and Age Analyses of Cortical Structure in the ABCD Study.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  20. Article

9 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

11 authors.

Aditi BhargavaCenter for Reproductive Sciences, San Francisco, CA, USA.ORCID 0000-0003-1334-0517
Arthur P ArnoldDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Debra A BangasserDepartment of Psychology and Neuroscience Program, Temple University, Philadelphia, PA, USA.
Kate M DentonCardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.
Arpana GuptaG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA, USA.
Lucinda M Hilliard KrauseCardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.
Emeran A MayerG. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA, USA.
Margaret McCarthyDepartment of Pharmacology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.
Walter L MillerCenter for Reproductive Sciences, San Francisco, CA, USA.
Armin RaznahanSection on Developmental Neurogenomics, Human Genetics Branch, National Institutes of Mental Health, Intramural Research Program, Bethesda, MD, USA.ORCID 0000-0002-5622-1190
Ragini VermaDiffusion and Connectomics In Precision Healthcare Research (DiCIPHR) lab, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Funding

Section on Developmental NeurogenomicsZIAMH002949 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI RAZNAHAN, ARMIN · 2016 to 2025
$30.0M
Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
Social Isolation and Discrimination as Stressors Influencing Brain-Gut Microbiome Alterations among Filipino and Mexican AmericanR01MD015904 · NIMHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHURCH, ARPANA · 2021 to 2025
$4.1M
Genetic Mechanisms in Klinefelter Syndrome-Related BehaviorsR01HD076125 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, JENTSCH, J. DAVID · 2014 to 2018
$2.3M
Coupling neuroimaging with CLARITY and single cell genomics to dissect sex differences in the developing brainR01HD100298 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, LERCH, JASON P. · 2020 to 2024
$2.2M
Biomedical Image Computing and Informatics ClusterS10OD023495 · OD · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2017 to 2017
$1.9M
Epigenetic regulation of myocardial ischemia/reperfusion injury by X chromosomeR01HL131182 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, EGHBALI, MANSOUREH · 2016 to 2019
$1.5M
Sry transgenic rats for investigation of XX vs. XY differences in phenotypesR21OD026560 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, DWINELL, MELINDA R · 2018 to 2019
$440k
Discriminating sex chromosome and hormonal effects on brain sexual dimorphismsR21HD090637 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, MACKENZIE-GRAHAM, ALLAN JAMES · 2017 to 2018
$428k
Sex differences in myocardial ischemia/reperfusion injuryR56HL119886 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, EGHBALI, MANSOUREH · 2014 to 2014
$350k
Role of the Gut Microbiome in Reward Network Alterations in ObesityR03DK121025 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHURCH, ARPANA · 2020 to 2021
$234k
NHLBI NIH HHS R01 HL131182NHLBI NIH HHS R56 HL119886NICHD NIH HHS R01 HD100298NICHD NIH HHS R21 HD090637NIDDK NIH HHS R03 DK121025NIDDK NIH HHS U54 DK120342NIH HHS R21 OD026560NIH HHS S10 OD023495NIMHD NIH HHS R01 MD015904
6 · The paper itself

Abstract

In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the "observer effect") and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the "sex" of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design.

Indexed as

Biomedical ResearchAnimalsFemaleHumansMaleNational Institutes of Health (U.S.)Sex CharacteristicsSex FactorsUnited Statesbrain-gutcardiovascular diseasechromosome complementgendersex differencessteroid hormones

Identifiers

PMID33704446
PMCPMC8348944

What OpenQuestion holds

Textmetadata
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.