Testosterone Administration During Energy Deficit Suppresses Hepcidin Concentrations and Increases Iron Utilization in Healthy Males (OR15-08-19)

Abstract

ObjectivesMilitary personnel are exposed to periods of energy deficit and stress, which is typically accompanied by reductions in testosterone concentrations and declines in iron status. Exogenous testosterone administration may increase erythropoiesis and iron availability.The objective of this study was to determine the effects of exogenous testosterone on iron homeostasis in healthy young males during energy deficit. MethodsFifty males (24.8 ± 5.0 y, 78.6 ± 12.2 kg) completed this randomized, double-blind, placebo-controlled trial. Participants were provided a eucaloric diet during a 2-week free-living phase (day 1–14). Following the free-living phase, participants completed a 4-week live-in phase (day 15–42). During the live-in phase participants were randomized to 200 mg testosterone enanthate/week (n = 24) or 1 mL sesame oil/week (placebo, n = 26) and were in an energy- and exercise-induced energy deficit equal to 53 ± 4%. Blood was collected on days 14 and 42 to determine concentrations of testosterone, hemoglobin, hematocrit, ferritin, hepcidin, and erythroferrone. Data are reported as change scores (mean ± SD). ResultsTotal testosterone concentrations increased with testosterone and declined with placebo (569 ± 271 nmol/L and −83 ± 142 nmol/L, P < 0.0001). Testosterone attenuated the decline in hemoglobin (−0.04 ± 0.7 g/L and −0.6 ± 0.8 g/dL, P < 0.01) and hematocrit (0.6 ± 2.2% and −1.3 ± 2.1%, P < 0.01) that occurred with placebo. Hepcidin (−3.7 ± 5.0 ng/mL and 2.1 ± 5.0 ng/mL, P < 0.001) and ferritin (−32.5 ± 38.6 ng/mL and 15.4 ± 41.2 ng/mL, P < 0.0001) were reduced with testosterone as compared to placebo. Erythroferrone (−0.5 ± 2.1 ng/mL and 0.5 ± 2.0 ng/mL, P = 0.11) did not differ when comparing testosterone to placebo. ConclusionsTestosterone administration during energy deficit suppressed hepcidin concentrations and increased iron utilization in healthy young males. The reduction in hepcidin with testosterone administration appears to occur through an erythroferrone-independent mechanism. Funding SourcesThe views expressed are those of the authors and do not reflect the official policy of the Army, DoD, or the U.S. Government. Supported by the Collaborative Research to Optimize Warfighter Nutrition II and III projects and the Defense Health Program Joint Program Committee-5.