Interplay of serum hepcidin with female sex hormones, metabolic syndrome, and abdominal fat distribution among premenopausal and postmenopausal women

Abstract
Background and purpose
Hepcidin is the central regulatory molecule of systemic iron homeostasis. Serum ferritin, insulin resistance (IR) and metabolic syndrome (MetS), female sex hormones, and abdominal fat distribution are related to each other and all are linked to menopausal state. Our study was the first to assess the impact of these parameters on hepcidin level among premenopausal women (group I) during the early follicular phase (group I-F) and mid-luteal-phase (group I-L) of the same reproductive cycle and among postmenopausal women (group II). Serum iron parameters, estrogen, progesterone and hepcidin, and plasma insulin were assessed. Abdominal subcutaneous fat (SCF) and peritoneal visceral fat (PVF) thickness were measured by unenhanced- CT. Group I and group II were divided into MetS and non-MetS subgroups.

Results
The entire group II and MetS-stratified subgroups had significant higher hepcidin level than corresponding group I-F and group I-L. Group I-L had significant higher hepcidin than group I-F. Among group I-F, group I-L, and group II, MetS subgroups had higher hepcidin but not hepcidin/ ferritin ratio (H/F) than corresponding non-MetS; and hepcidin had positive correlations with ferritin, insulin, IR, and SCF. In group I-F and group II, hepcidin had positive correlations with estrogen and progesterone; hepcidin levels increase significantly and linearly with increasing number of MetS features; and cut off values of hepcidin for prediction of MetS were 5.8 ≥ and ≥ 10.3 ng/ml respectively. Main contributors to hepcidin were iron and ferritin in all groups, SCF and progesterone in group I-F, and insulin, progesterone, and MetS in group II. H/F ratio was higher in group II.

Conclusion
Postmenopausal state (postMS), MetS, and luteal phase are independently associated with high hepcidin level. Serum iron parameters (iron and ferritin) as main regulators of hepcidin are preserved regardless of menopausal state. Its regulation differs based on menopausal state: IR, MetS, and progesterone in postMS meanwhile abdominal SCF and progesterone in premenopausal states. Despite positive associations of estrogen and progesterone with hepcidin, they do not explain its higher level in postMS. Hepcidin levels linearly increase with number of Mets feature and it had high sensitivity for diagnosis of MetS.