Pubertal upregulation of erythropoiesis in boys is determined primarily by androgen

Objectives To study the relative roles of androgens and the growth hormone-insulin-like growth factor I (GH-IGF-I) system in the regulation of erythropoiesis in boys during puberty. Study design We treated 23 boys with constitutional delay of puberty with low-dose testosterone (T), in combination with either a potent aromatase inhibitor, letrozole (Lz; 2.5 mg/d), or placebo (P). The study design was randomized, double-blinded, and placebo-controlled between the treated groups. Treatment with T + Lz was associated with high T and low IGF-I concentrations, whereas treatment with T + P resulted in moderately increased T and high IGF-I concentrations. Results The blood hemoglobin concentration increased by 1.6 g/dL in T + Lz-treated boys, despite their low IGF-I concentrations. The estimated red blood cell volume increased more in T + Lz-treated than in T + P-treated boys (349 vs 174 mL, respectively, P =.01). Serum T concentrations during the treatment period correlated with the 12-month increments in hemoglobin and red blood cell volume. The changes in blood hemoglobin concentration and RBC in T + Lz-treated boys were similar to those we observed in a population of normal adolescent boys in the late stages of puberty. Conclusions The pubertal increase in hemoglobin concentration in boys is related to direct androgen effects.