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Cited by 70Exercise and Physiological ResponsesEstrogen and related hormone effectsCardiovascular and exercise physiology

Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism

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Oosthuyse, Tanja, Strauss, Juliette A., Hackney, Anthony C.·2022·European Journal of Applied Physiology
DOI 10.1007/s00421-022-05090-3
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Abstract

Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-β-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.

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  • Recent guidelines provide recommendations on the conditions under which female sex hormones need to be considered.

    “these guidelines provide recommendations on the conditions under which female sex hormones need to be considered [1,8,11]”

    From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [8]

    The Conclusion and perspectives (page unavailable) recommends considering menstrual phase in specific exercise and nutrition contexts, including carbohydrate-restricted exercise and recovery planning. The source calls itself a review, however, rather than a guideline, so it supports the substance of the recommendations but not the description of this paper as a guideline. (LLM, conf=0.82)

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Research works printed but not linked: 1

  1. Häggström M, Richfield D (2014) Diagram of the pathways of human steroidogenesis. WikiJ Med. https:// doi. org/ 10. 15347/ 2FWJM/ 2F2014. 005 · DOI

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Authors
Oosthuyse, T., Strauss, J. A., & Hackney, A. C.
Affiliations
  • University of Cape Town (ZA)
  • Liverpool John Moores University (GB)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Oosthuyse, Tanja
ORCID
Venue
European Journal of Applied Physiology
Publisher
Springer Science and Business Media LLC
Published
2022-11-19
Volume
123
Issue
3
Pages
423-450
ISSN
  • 0020-9376 (ISSN-L)
  • 1439-6319
  • 1439-6327
DOI
10.1007/s00421-022-05090-3
OpenAlex
W4309404830
Cited by
70
References
163
Citations by year
2026: 10 · 2025: 21 · 2024: 27 · 2023: 12
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Applied Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion)
  • University of the Witwatersrand, Johannesburg Institutional Repository on DSpace (University of the Witwatersrand, Johannesburg) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
female athletes, menstrual cycle, exercise metabolism, estradiol, progesterone, ovarian hormones, nuclear receptors, membrane-bound estrogen receptor, exercise-induced muscle damage, antioxidant enzymes, GLUT4, gluconeogenesis, fat oxidation, protein degradation, satellite cells, muscle strength, estrogen-progesterone ratio, sex differences in exercise response
MeSH terms
Estradiol, Female, Follicular Phase, Humans, Luteal Phase, Male, Menstrual Cycle, Menstruation

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