Purpose: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O_2peak) and tHb in both males and females.

Methods: We included 48 healthy, recreational to trained males (n = 24, mean ± standard deviation V̇O_2peak of 55 ± 5 ml O₂ × kg^-1 × min^-1) and females (n = 24; V̇O_2peak of 46 ± 4 ml O₂ × kg^-1 × min^-1) in a counter-balanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O_2peak, and tHb were determined before and after intravenous injections of either rHuEPO (9 IU × kg bw^-1 epoetin β) or saline (0.9% NaCl) three times weekly for 4 weeks.

Results: A time × treatment effect (P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output (MPO) increased by 4.1 ± 4.2% (P < 0.001). Likewise, a time × treatment effect (P < 0.001) existed for V̇O_2peak, where the rHuEPO group improved V̇O_2peak and peak aerobic power by 4.2 ± 6.1% (P < 0.001) and 2.9 ± 4.0% (P < 0.01), respectively. A time × treatment effect (P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7 ± 3.4% (P < 0.001). A main effect of 'sex' alone was also evident (P < 0.001) but no sex-specific interactions were found. No changes were observed in the placebo group for MPO, V̇O_2peak, peak aerobic power or tHb.

Conclusion: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.