Pubertal upregulation of erythropoiesis in boys is determined primarily by androgen

J Pediatr. 2005 Feb;146(2):245-52. doi: 10.1016/j.jpeds.2004.09.002.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Androgens / blood
  • Androgens / metabolism
  • Androgens / physiology*
  • Aromatase Inhibitors / therapeutic use
  • Child
  • Double-Blind Method
  • Drug Therapy, Combination
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Erythropoiesis / drug effects*
  • Growth Hormone / metabolism
  • Hemoglobins / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / physiology
  • Letrozole
  • Male
  • Nitriles / therapeutic use*
  • Puberty / physiology
  • Puberty, Delayed / drug therapy*
  • Puberty, Delayed / metabolism
  • Testosterone / blood
  • Testosterone / metabolism
  • Testosterone / therapeutic use*
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Up-Regulation


  • Androgens
  • Aromatase Inhibitors
  • Hemoglobins
  • Nitriles
  • Triazoles
  • Testosterone
  • Insulin-Like Growth Factor I
  • Letrozole
  • Growth Hormone