Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women
Open accessAbstract
Hepcidin regulates serum iron levels, and its dosage is used in differential diagnostic of iron-related pathologies. We used the data collected in the HEPMEN (named after HEPcidin during MENses) study to investigate the joint dynamics of serum hepcidin and iron during the menstrual cycle in healthy women. Ninety menstruating women were recruited after a screening visit. Six fasting blood samples for determination of iron-status variables were taken in the morning throughout the cycle, starting on the second day of the period. Non-linear mixed effect models were used to describe the evolution of iron and hepcidin. Demographic and medical covariates were tested for their effect on model parameters. Parameter estimation was performed using the SAEM algorithm implemented in the Monolix software. A general pattern was observed for both hepcidin and iron, consisting of an initial decrease during menstruation, followed by a rebound and stabilising during the second half of the cycle. We developed a joint model including a menstruation-induced decrease of both molecules at the beginning of the menses and a rebound effect after menses. Iron stimulated the release of hepcidin. Several covariates, including contraception, amount of blood loss and ferritin, were found to influence the parameters. The joint model of iron and hepcidin was able to describe the fluctuations induced by blood loss from menstruation in healthy non-menopausal women and the subsequent regulation. The HEPMEN study showed fluctuations of iron-status variables during the menstrual cycle, which should be considered when using hepcidin measurements for diagnostic purposes in women of child-bearing potential.
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In the late follicular phase (days 6-14), the gradual rise in estrogen maintains low hepcidin activity, enabling iron absorption and recycling in the days following menses.
“In the late follicular phase (days 6–14), the gradual rise in estrogen maintains low hepcidin activity, enabling iron absorption and recycling in the days following menses [320].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [320]
The Evolution of Iron-Status Variable During the Study section reports that hepcidin decreased during menses but rebounded after menses, reaching above-baseline concentrations; the Sampling Design section places that rebound between days 6 and 12. This is contrary to the claim that hepcidin remains low on days 6–14. The cited passages do not establish estrogen as the cause. (LLM, conf=0.87)
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Experimental — accuracy not yet measuredPrevious research results demonstrate a rebound in hepcidin, serum iron, and transferrin saturation post-ovulation that stabilizes during the luteal phase.
“Previous research results demonstrate a rebound in hepcidin, serum iron, and transferrin saturation post-ovulation that stabilizes during the luteal phase [320].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [320]
The section “Evolution of Iron-Status Variable During the Study” reports a rebound in iron and hepcidin after menses, a similar pattern in transferrin saturation, and stabilization during the second half of the cycle. It does not place the rebound post-ovulation; the Discussion describes it as occurring mid-cycle. (LLM, conf=0.88)
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Flagged first, then by citations
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Cited by
Sorted by citations
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Background
- Authors
- Angeli, A., Lainé, F., Lavenu, A., Ropert, M., Lacut, K., Gissot, V., Sacher-Huvelin, S., Jezequel, C., Moignet, A., Laviolle, B., & Comets, E.
- Affiliations
- Inserm (FR)
- Corresponding author
- Comets, Emmanuelle
- ORCID
- Venue
- The AAPS Journal
- Published
- 2016-02-02
- Volume
- 18
- Issue
- 2
- Pages
- 490-504
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC4779110
- OpenAlex
- W2274448441
- Cited by
- 40
- References
- 43
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 15 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 3
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- The AAPS Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, serum iron, menstrual cycle, iron status, menstruation, blood loss, ferritin, contraception, joint modeling, women of reproductive age, iron regulation
- MeSH terms
- Adult, Anti-Infective Agents, Female, Humans, Iron, Menstrual Cycle, Models, Biological, Young Adult, Healthy Volunteers, Hepcidins
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