title: Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women.
abstract: 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.
authors: INSERM CIC 1414, Rennes, France.
authors: Adeline
authors: A
authors: Angeli
authors: INSERM CIC 1414, Rennes, France.|INSERM U991, Rennes, France.|CHU, Rennes, France.
authors: Fabrice
authors: F
authors: Lainé
authors: INSERM CIC 1414, Rennes, France.|University Rennes 1, Rennes, France.
authors: Audrey
authors: A
authors: Lavenu
authors: INSERM U991, Rennes, France.|CHU, Rennes, France.
authors: Martine
authors: M
authors: Ropert
authors: INSERM CIC 1412, Brest, France.
authors: Karine
authors: K
authors: Lacut
authors: INSERM CIC 1415, Tours, France.
authors: Valérie
authors: V
authors: Gissot
authors: INSERM CIC 1413, Nantes, France.|IMAD, CHU Hotel Dieu, Nantes, France.
authors: Sylvie
authors: S
authors: Sacher-Huvelin
authors: INSERM CIC 1414, Rennes, France.|CHU, Rennes, France.
authors: Caroline
authors: C
authors: Jezequel
authors: INSERM CIC 1414, Rennes, France.|CHU, Rennes, France.
authors: Aline
authors: A
authors: Moignet
authors: INSERM CIC 1414, Rennes, France.|CHU, Rennes, France.|University Rennes 1, Rennes, France.
authors: Bruno
authors: B
authors: Laviolle
authors: INSERM CIC 1414, Rennes, France. emmanuelle.comets@inserm.fr.|University Rennes 1, Rennes, France. emmanuelle.comets@inserm.fr.|INSERM IAME UMR 1137, Paris, France. emmanuelle.comets@inserm.fr.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France. emmanuelle.comets@inserm.fr.
authors: Emmanuelle
authors: E
authors: Comets
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood*; D005260:Female; D064368:Healthy Volunteers; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D008597:Menstrual Cycle / Q000097:blood*; D008954:Models, Biological; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D064451:Hepcidins; D007501:Iron
keywords: hepcidin; iron; iron regulation; menstrual cycle; turnover model