Mechanisms of sex differences in exercise capacity
Open accessAbstract
Sex differences are an important component of National Institutes of Health rigor. The goal of this investigation was to test the hypothesis that female mice have greater exercise capacity than male mice, and that it is due to estrogen, nitric oxide, and myosin heavy chain expression. Female C57BL6/J wild-type mice exhibited greater ( P < 0.05) maximal exercise capacity for running distance (489 ± 15 m) than age-matched male counterparts (318 ± 15 m), as well as 20% greater work to exhaustion. When matched for weight or muscle mass, females still maintained greater exercise capacity than males. Increased type I and decreased type II myosin heavy chain fibers in the soleus muscle from females are consistent with fatigue resistance and better endurance in females compared with males. After ovariectomy, female mice no longer demonstrated enhanced exercise, and treatment of male mice with estrogen resulted in exercise capacity similar to that of intact females (485 ± 37 m). Nitric oxide synthase, a downstream target of estrogen, exhibited higher activity in female mice compared with male mice, P < 0.05, whereas ovariectomized females exhibited nitric oxide synthase levels similar to males. Nitric oxide synthase activity also increased in males treated with chronic estrogen to levels of intact females. Nitric oxide synthase blockade with N ω-nitro-l-arginine methyl ester eliminated the sex differences in exercise capacity. Thus estrogen, nitric oxide, and myosin heavy chain expression are important mechanisms mediating the enhanced exercise performance in females.
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Women utilize more lipid than men, largely attributable to sex-specific hormonal influences and epigenetic adaptations to endurance exercise.
“women utilize more lipid when compared to men and this is largely attributable to sex-specific hormonal influences and epigenetic adaptations to endurance exercise [86,175–177].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [86]
The Discussion (page unavailable) links estrogen to greater exercise capacity in female mice, not to lipid utilization in women. Searches for lipid utilization and epigenetic adaptations found no passage addressing either part of the attributed claim. (LLM, conf=0.75)
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- Authors
- Oydanich, M., Babici, D., Zhang, J., Rynecki, N., Vatner, D. E., & Vatner, S. F.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Vatner, Stephen F.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2019-06-01
- Volume
- 316
- Issue
- 6
- Pages
- R832-R838
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC6734069
- OpenAlex
- W2942330094
- Cited by
- 55
- References
- 30
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 5 · 2020: 5 · 2019: 3
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute on Aging (U.S. National Institute on Aging) (R21AG053514)
- HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI) (R01HL119464, R01HL137405, R01HL106511, R01HL124282, R01HL137368, R01HL102472, R01HL130848)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- sex differences, exercise capacity, estrogen, nitric oxide synthase, myosin heavy chain, ovariectomy, endurance, fatigue resistance, soleus muscle, L-NAME
- MeSH terms
- Animals, Estrogens, Female, Male, Mice, Inbred C57BL, Nitric Oxide, Ovariectomy, Physical Conditioning, Animal, Sex Characteristics, Sex Factors, Exercise Tolerance, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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