Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk–benefit

Abstract

Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would surely not be recommended. The use of recombinant human erythropoietin (rHuEPO) to enhance performance in cycling is very common. A qualitative systematic review of the available literature was performed to examine the evidence for the ergogenic properties of this drug, which is normally used to treat anaemia in chronic renal failure patients. The results of this literature search show that there is no scientific basis from which to conclude that rHuEPO has performance-enhancing properties in elite cyclists. The reported studies have many shortcomings regarding translation of the results to professional cycling endurance performance. Additionally, the possibly harmful side-effects have not been adequately researched for this population but appear to be worrying, at least. The use of rHuEPO in cycling is rife but scientifically unsupported by evidence, and its use in sports is medical malpractice. What its use would have been, if the involved team physicians had been trained in clinical pharmacology and had investigated this properly, remains a matter of speculation. A single well-controlled trial in athletes in real-life circumstances would give a better indication of the real advantages and risk factors of rHuEPO use, but it would be an oversimplification to suggest that this would eradicate its use.

Little soldiers in their cardboard cells

“…The 6.3% (lowest increase in Table 1 of Heuberger et al [1]) and 9.3% gain (highest gain in Table 1 of Heuberger et al [1]) in V O2 max by the use of EPO make up between 10 and 20% of the maximal gain as shown by Bouchard et al [4].…”

“…As medical professionals with long-standing experience in sports physiology and sports medicine in both the academic and sports world, we would like to comment on the recent manuscript by Heuberger et al [1] regarding the lack of evidence for the efficacy and the negative riskbenefit of erythropoietin (EPO) use in cycling. Indeed, it has been a moving sports summer, with the confession by dozens of professional cyclists of the use of, among other substances, erythropoietin, with the public confession of seven times Tour de France winner Lance Armstrong as the anticlimax.…”

“…In their manuscript, Heuberger et al [1] provided evidence only for nonadherence to recognized medical standards based on possible general side-effects of EPO, but it would have strengthened their well-intended message if they had included a practical case. These are, however, rare for EPO use.…”

“…Heuberger et al [1] also state that the claimed performance-enhancing effects of EPO in cycling are unsupported by scientific evidence.The evidence provided within their manuscript is, in our opinion, based on erroneous interpretations of the published literature cited.…”

Gender difference in platelet aggregation and reactivity induced by recombinant human erythropoietin

“…Hence, on this basis, the present work has been performed to study the ex vivo effects of rhEPO in a small cohort of young and healthy individuals (15 males and 14 females). Platelet reactivity and aggregation patterns which, in turn, may cause thrombotic disorders [3], have been evaluated.Treatments with rhEPO 0.2 IU and 0.4 IU were performed. Platelet aggregation induced by adenosine diphosphate (ADP) or collagen, was evaluated as stated in the literature (see Supporting Information) [4].…”