Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis

• Published in: The journal of clinical endocrinology and metabolism 2010-10, Vol.95 (10), p.4743-4747
• Main Authors: Bachman, Eric, Feng, Rui, Travison, Thomas, Li, Michelle, Olbina, Gordana, Ostland, Vaughn, Ulloor, Jagadish, Zhang, Anqi, Basaria, Shehzad, Ganz, Tomas, Westerman, Mark, Bhasin, Shalender
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging - blood; Aging - physiology; Antimicrobial Cationic Peptides - blood; Antimicrobial Cationic Peptides - metabolism; Biological and medical sciences; Dose-Response Relationship, Drug; Double-Blind Method; Down-Regulation - drug effects; Drug Administration Schedule; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Hepcidins; Humans; Injections; Leuprolide - administration & dosage; Male; Medical sciences; Middle Aged; Original; Polycythemia - chemically induced; Testosterone - administration & dosage; Testosterone - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-0864

Context: The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown. Objective: The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin. Participants: Healthy younger men (ages 19–35 yr; n = 53) and older men (ages 59–75 yr; n = 56) were studied. Methods: Weekly doses of testosterone enanthate (25, 50, 125, 300, and 600 mg) were administered over 20 wk, whereas endogenous testosterone was suppressed by monthly GnRH agonist administration. Blood and serum parameters from each individual were measured at wk 0, 1, 2, 4, 8, and 20. Longitudinal analyses were performed to examine the relationship between hepcidin, hemoglobin, hematocrit, and testosterone while controlling for potential confounders. Results: High levels of testosterone markedly suppressed serum hepcidin within 1 wk. Hepcidin suppression in response to testosterone administration was dose-dependent in older men and more pronounced than in young men, and this corresponded to a greater rise in hemoglobin in older men. Serum hepcidin levels at 4 and 8 wk were predictive of change in hematocrit from baseline to peak levels. Conclusion: Testosterone administration is associated with suppression of serum hepcidin. Greater increases in hematocrit in older men during testosterone therapy are related to greater suppression of hepcidin. Testosterone suppresses the iron regulatory peptide hepcidin in men, and this effect is more pronounced in older men who also experience greater erythrocytosis.