Hematological adaptations and detection of recombinant human erythropoietin combined with chronic hypoxia

This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with chronic hypoxia provided an additive erythropoietic response and whether the Athlete Biological Passport (ABP) sensitivity improved with hypoxia. Two interventions were completed, each containing four weeks baseline, four weeks exposure at sea-level or 2,320m of altitude and four weeks follow-up. Participants were randomly assigned to 20 IU·kg bw-1 rhEpo or placebo injections every second day for three weeks during the exposure period at sea-level (rhEpo n=25, placebo n=9) or at altitude (rhEpo n=12, placebo n=27). Venous blood was analyzed weekly. Combining rhEpo and hypoxia induced larger changes compared with rhEpo or hypoxia alone for [Hb] (p < 0.001, p > 0.05, respectively), reticulocyte percentage (p < 0.001) and OFF-hr score (p < 0.01, p < 0.001, respectively). The most pronounced effect was observed for reticulocyte percentage with up to ~35% (p < 0.001) and ~45% (p < 0.001) higher levels compared with rhEpo or hypoxia only, respectively. The ABP sensitivity for the combined treatment was 54 and 35 percentage points higher for [Hb] (p < 0.05) and reticulocyte percentage (p < 0.05), respectively, but similar for OFF-hr score, compared with rhEpo at sea-level. Across any time point, [Hb] and OFF-hr score combined identified 14 unique true-positive participants (56%) at sea-level and 12 unique true-positive participants (100%) at altitude. However, a concurrent reduction in specificity existed at altitude. In conclusion, rhEpo treatment combined with hypoxic exposure provided an additive erythropoietic response compared to rhEpo or hypoxic exposure alone. Correspondingly, ABP was more sensitive to rhEpo at altitude than at sea-level, but a compromised specificity existed with hypoxic exposure.