Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women

Adeline Angeli (1) , Fabrice Lainé (1, 2, 3) , Audrey Lavenu (4, 1) , Martine Ropert (5, 2, 3) , Karine Lacut (6, 7) , Valérie Gissot (8) , Sylvie Sacher-Huvelin (9) , Caroline Jezequel (10, 1) , Aline Moignet (3, 1) , Bruno Laviolle (1, 3, 11) , Emmanuelle Comets (1, 12)

1 CIC - Centre d'Investigation Clinique [Rennes]
2 Foie, métabolismes et cancer
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 UR Médecine - Université de Rennes - Faculté de Médecine
5 Centre de référence des surcharges en fer rares d'origine génétique
6 CIC - Brest - Centre d'Investigation Clinique
7 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
8 CIC - Tours
9 CIC
10 Service des Maladies de l'Appareil Digestif [CHU Rennes]
11 Service de Pharmacologie [Rennes]
12 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution

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

Mots clés: turnover model; menstrual cycle; iron regulation; Iron; Hepcidin

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Adeline Angeli, Fabrice Lainé, Audrey Lavenu, Martine Ropert, Karine Lacut, et al.. Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women. AAPS Journal, 2016, 18 (2), pp.490-504. ⟨10.1208/s12248-016-9875-4⟩. ⟨hal-01274215⟩