testosterone regulates erythropoiesis in numerous mammalian species, including humans of both sexes (1). Excessive erythrocytosis is the most common serious adverse event associated with testosterone therapy in older men (2). However, the mechanisms by which testosterone stimulates erythropoiesis remain poorly understood. It has been suggested that testosterone stimulates erythropoietin secretion and directly stimulates erythroid progenitor cells (3, 4). We showed previously, however, that testosterone dose-dependently increases hemoglobin and hematocrit, but without an associated increase in erythropoietin (5). In addition, testosterone has minimal proliferative effect on purified (CD34_) erythroid progenitors ex vivo (6). We considered the hypothesis that testosterone increases hematocrit by suppressing the master iron regulatory peptide hepcidin, thus resulting in increased bioavailable iron. Hepcidin is a liver-derived peptide that binds to and degrades the iron channel ferroportin (7, 8). Increased hepcidin, in response to infection and inflammation restricts systemic iron bioavailability and results in mild anemia in chronic disease (9). Low hepcidin, conversely, is associated with increased iron absorption, increased systemic iron transport, and erythropoiesis. To test the hypothesis that testosterone suppresses serum hepcidin, we measured serum hepcidin levels in a testosterone dose response study, in which healthy younger (19–35 yr old) and older (59–75 yr) men were administered a long-acting GnRH agonist to suppress endogenous testosterone production, along with varying doses of testosterone enanthate for 20 wk (10, 11). This design produced cohorts of subjects with graded, stable levels of testosterone within 4wkthat were maintained for 20 wk. This intervention resulted in dose-dependent increases in hematocrit and hemoglobin that were greater in older than younger men (5). We measured serum hepcidin in serum samples from these men, and tested the hypothesis that age-related differences in erythropoietic response are related to the magnitude of hepcidin suppression. We also assessed whether early changes in hepcidin levels predict subsequent changes in hematocrit and hemoglobin. Bachman E, Feng R, Travison T, et al. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis. J Clin Endocrinol Metab:jc.2010-0864. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis 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.