Menstrual cycle affects iron homeostasis and hepcidin following interval running exercise in endurance-trained women

Abstract

Purpose: Menstrual cycle phase affects resting hepcidin levels, but such effects on the hepcidin response to exercise are still unclear. Thus, we investigated the hepcidin response to running during three different menstrual cycle phases.

Methods: Twenty-one endurance-trained eumenorrheic women performed three identical interval running protocols during the early-follicular phase (EFP), late-follicular phase (LFP), and mid-luteal phase (MLP). The protocol consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed, with 90-s recovery. Blood samples were collected pre-exercise and at 0 h, 3 h and 24 h post-exercise.

Results: Data presented as mean ± SD. Ferritin were lower in the EFP than the LFP (34.82 ± 16.44 vs 40.90 ± 23.91 ng/ml, p = 0.003), while iron and transferrin saturation were lower during the EFP (58.04 ± 19.70 µg/dl, 14.71 ± 5.47%) compared to the LFP (88.67 ± 36.38 µg/dl, 22.22 ± 9.54%; p < 0.001) and the MLP (80.20 ± 42.05 µg/dl, 19.87 ± 10.37%; p = 0.024 and p = 0.045, respectively). Hepcidin was not affected by menstrual cycle (p = 0.052) or menstrual cycle*time interaction (p = 0.075). However, when comparing hepcidin at 3 h post-exercise, a moderate and meaningful effect size showed that hepcidin was higher in the LFP compared to the EFP (3.01 ± 4.16 vs 1.26 ± 1.25 nMol/l; d = 0.57, CI = 0.07-1.08). No effect of time on hepcidin during the EFP was found either (p = 0.426).

Conclusion: The decrease in iron, ferritin and TSAT levels during the EFP may mislead the determination of iron status in eumenorrheic athletes. However, although the hepcidin response to exercise appears to be reduced in the EFP, it shows no clear differences between the phases of the menstrual cycle (clinicaltrials.gov: NCT04458662).

Keywords: Anemia; Athlete monitoring; Female athletes; Inflammation; Interleukin-6; Iron deficiency.

Conflict of interest statement

No conflicts of interest, financial or otherwise, to declare by the authors.

© 2022. The Author(s).

Figures

Fig. 1

Experimental protocol performed in the EFP, LFP, and MLP of the menstrual cycle. EFP early-follicular phase, FSH follicle-stimulating hormone, LFP late-follicular phase, LH luteinizing hormone, MLP mid-luteal phase, 0 h, 0 h post-exercise, 3 h, 3 h post-exercise, 24 h, 24 h post-exercise

Fig. 2

Mean (SEM) serum hepcidin concentrations and the individual hepcidin response of each participant to the interval running protocol in the early-follicular phase (circles), late-follicular phase (squares) and mid-luteal phase (triangles). Each color represents a different participant. Symbols above the arrows indicate post-hoc differences for the factor Time. Post-0 h, 0 h post-exercise; Post-3 h, 3 h post-exercise; Post-24 h, 24 h post-exercise *Significantly different from Pre-exercise. $ Significantly different from Post-0 h. # Significantly different from Post-3 h

Fig. 3

Mean (SEM) serum IL-6 (a), TNF-⍺ (b) and CRP (c) concentrations and each participant's individual response to the interval running protocol in the early-follicular phase (circles), late-follicular phase (squares) and mid-luteal phase (triangles). Each color represents a different participant. Symbols above the arrows indicate post-hoc differences for the factor Time. CRP C-reactive protein, Post-0 h, 0 h post-exercise, Post-3 h, 3 h post-exercise, Post-24 h, 24 h post-exercise, TNF-⍺ tumor necrosis factor alpha. Symbols above the arrows indicate post-hoc differences for the factor Time. *Significantly different from Pre-exercise. $ Significantly different from Post-0 h

Fig. 4

Mean (SEM) serum iron (a), TSAT (b), ferritin (c) and transferrin (d) concentrations and each participant's individual response to the interval running protocol in the early-follicular phase (circles), late-follicular phase (squares) and mid-luteal phase (triangles). Each color represents a different participant. Symbols above the arrows indicate post-hoc differences for the factor Time. Post-0 h, 0 h post-exercise, Post-3 h, 3 h post-exercise, Post-24 h, 24 h post-exercise, TSAT transferrin saturation. Symbols above the arrows indicate post-hoc differences for the factor Time. *Significantly different from Pre-exercise. $ Significantly different from Post-0 h. # Significantly different from Post-3 h