Recombinant human erythropoietin (rhEPO), which increases red cell mass, is
one of the most abused substances in sport. Abuse is currently undetectabl
e by the only direct routine method, immunoassay, since blood and urine rhE
PO are immunologically indistinguishable from endogenous EPO. Elevated EPO
levels are only detectable several days after rhEPO administration. Indirec
t parameters have therefore been introduced, primarily the haematocrit leve
l, but also markers of functional iron deficiency during or after rhEPO adm
inistration (hypochromic red cells and reticulocytes, serum transferrin rec
eptors, ferritin levels) and, in the urine, fibrin degradation products. Al
though iron status indices have yielded promising results, athletes are cur
rently banned solely on the basis of their haematocrit. Yet various factors
can cause false positive haematocrit results with potentially fatal conseq
uences to athletes' careers. Until new direct assays such as liquid chromat
ography-mass spectrometry have been evaluated and introduced, efforts must
be directed at using a battery of tests to increase the sensitivity and spe
cificity and reduce the number of false positives and false negatives.