The Role of Testosterone in the Utilization of Iron in Erythropoiesis

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SAT 134-160-Male Reproductive Endocrinology and Male Reproductive Tract (posters)
Bench to Bedside
Saturday, April 2, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SAT 149
Sandeep S Dhindsa*1, Husam Ghanim2, Manav Batra2, Kelly Green3, Sanaa Abuaysheh4, Ajay Chaudhuri5, Ajantha Nithi4 and Paresh Dandona5
1Texas Tech University Health Sciences Center at the Permian Basin, Odessa, TX, 2University at Buffalo, Buffalo, NY, 3SUNY at Buffalo, 4Suny at Buffalo, 5Diabetes and Endocrinology Center of Western New York, Buffalo, NY
Since the syndrome of hypogonadotropic hypogonadism (HH) is associated with anemia and the administration of testosterone restores hematocrit to normal, we investigated the potential mechanisms which may contribute to it. We measured serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. 44 men had HH (defined as free testosterone <5ng/dl along with low or normal LH concentrations) while 50 were eugonadal. Hematocrit concentrations were lower in hypogonadal men (41.2±3.8% vs. 43.8±3.2%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin, iron or transferrin saturation or in ferroportin expression in MNC among hypogonadal and eugonadal men. Men with HH were randomized to testosterone treatment (200 mg i.m., every two weeks) or placebo (saline 1ml every 2 weeks) for 24 weeks. 20 men in testosterone group and 14 men in placebo group completed the study. Free testosterone concentrations increased from 4.5±1.3 to 13.8±4.1ng/dl (p<0.001) after testosterone therapy but did not change in placebo group. The hematocrit increased from 42.0±2.7% to 45.4±4.6% (p<0.001) but did not change after placebo (40.7±2.9% to 41.6±3.1%, p=0.22). There was a 30±7% decrease in plasma hepcidin (p<0.01) and 29±8% increase in erythropoietin concentrations (p<0.05) after testosterone therapy. There was no significant change in iron or ferritin concentrations but transferrin concentration increased by 21±7% and transferrin saturation decreased by 30±10% (p<0.01). Ferroportin mRNA expression in MNC increased by 70±13% (p<0.01) at 4 weeks and 15 weeks but came back to baseline at 24 weeks after testosterone therapy when the hematocrit normalized. There was no change in any of these parameters after placebo. We conclude that the administration of testosterone to restore normal testosterone concentration led to a significant increase in plasma erythropoietin concentrations, reduction in plasma hepcidin concentration, marked increase in ferroportin expression which was transient, a smaller but significant increase in transferrin and a small reduction in plasma iron concentrations. Clearly, therefore, the increase in hematocrit is supported by an increase in erythropoietin and an increase in iron transport through an increase in ferroportin. This increase is probably through the known suppression of hepcidin which suppresses ferroportin expression.

Nothing to Disclose: SSD, HG, MB, KG, SA, AC, AN, PD

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