Menstrual cycle rhythmicity: metabolic patterns in healthy women
Open accessAbstract
The menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids were collected at four timepoints in the menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary luteinizing hormone and self-reported menstrual cycle timing were used for a 5-phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase, possibly indicative of an anabolic state during the progesterone peak and recovery during menstruation and the follicular phase. The reduced metabolite levels observed may represent a time of vulnerability to hormone related health issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These results provide a foundation for further research on cyclic differences in nutrient-related metabolites and may form the basis of novel nutrition strategies for women.
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Progesterone functions catabolically to increase amino acid oxidation and decreases muscle protein synthesis.
“functions catabolically to increase amino acid oxidation and decreases muscle protein synthesis [78–81]”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [78]
The Discussion interprets lower luteal-phase amino acid levels as supporting progesterone’s anabolic amino acid use and protein biosynthesis for endometrial growth—the opposite of the attributed catabolic action. The paper does not report increased amino acid oxidation or decreased muscle protein synthesis; its discussion of protein synthesis concerns the endometrium, not muscle. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredMetabolic function is coordinated with the menstrual cycle to ensure optimal physiological conditions for fertilization, implantation, pregnancy, parturition and lactation.
“Similarly, metabolic function is coordinated with the menstrual cycle to ensure optimal physiological conditions for fertilization, implantation, pregnancy, parturition and lactation [71].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [71]
The Discussion (page not provided) reports that metabolism changes in synchrony with menstrual-cycle phases and suggests that luteal-phase changes may support endometrial thickening in preparation for pregnancy. It does not establish that this coordination ensures optimal conditions for fertilization, implantation, pregnancy, parturition, and lactation. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn the menstrual cycle, pituitary gonadotropins (follicle-stimulating and luteinizing hormones) and ovarian hormones (estrogen and progesterone) show infradian rhythmicity.
“In the menstrual cycle, pituitary gonadotropins (follicle-stimulating and luteinizing hormones) and ovarian hormones (estrogen and progesterone) show infradian rhythmicity ( Figure 3 ) [ 87 , 88 ].”
From Physiological Rhythms and Biological Variation of Biomolecules: The Road to Personalized Laboratory Medicine (2023) · cites this paper as [88]
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- Authors
- Draper, C. F., Duisters, K., Weger, B., Chakrabarti, A., Harms, A. C., Brennan, L., Hankemeier, T., Goulet, L., Konz, T., Martin, F. P., Moco, S., & van der Greef, J.
- Affiliations
- Leiden University (NL)
- University College Dublin (IE)
- Corresponding author
- Draper, C. F.
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-10-01
- Volume
- 8
- Issue
- 1
- Pages
- 14568-14568
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6167362
- OpenAlex
- W2893363828
- Cited by
- 221
- References
- 96
- Citations by year
- 2026: 27 · 2025: 35 · 2024: 37 · 2023: 43 · 2022: 30 · 2021: 26 · 2020: 17 · 2019: 5 · 2018: 1
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-04-03)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- University College Dublin
- Universiteit Leiden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- menstrual cycle, circadian rhythm, metabolomics, lipidomics, luteal phase, follicular phase, progesterone, estradiol, neurotransmitter precursors, glutathione metabolism, urea cycle, 4-pyridoxic acid, 25-hydroxyvitamin D, amino acids, micronutrients, premenopausal women, premenstrual syndrome, premenstrual dysphoric disorder, nutritional strategies
- MeSH terms
- Adult, Biological Factors, Blood Chemical Analysis, Chromatography, Gas, Chromatography, Liquid, Female, Humans, Menstrual Cycle, Periodicity, Mass Spectrometry, Urinalysis, Metabolomics, Metabolome, Young Adult, Healthy Volunteers
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