A novel method utilising markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes.
OBJECTIVE
The use of recombinant human erythropoietin (r-HuEPO) to enhance athletic performance is prohibited. Existing tests cannot readily differentiate between exogenous and endogenous EPO. Therefore the aim of our study was to investigate possible indirect detection of r-HuEPO use via blood markers of altered erythropoiesis.


METHODS
Twenty-seven recreational athletes were assigned to three groups prior to a 25 day drug administration phase, with the following protocols: EPO+IM group (n = 10), 50 Ukg(-1) r-HuEPO at a frequency of 3wk(-1), 100 mg intramuscular (IM) iron 1wk(-1) and a sham iron tablet daily; EPO+OR group (n = 8), 50 U.kg(-1) r-HuEPO 3wk(-1), sham iron injection 1wk(-1) and 105 mg of oral elemental iron daily; placebo group (n = 9), sham r-HuEPO injections 3wk(-1), sham iron injections 1wk(-1) and sham iron tablets daily. Each group was monitored during and for 4 weeks after drug administration.


RESULTS
Models incorporating combinations of the variables reticulocyte hematocrit (RetHct), serum EPO, soluble transferrin receptor, hematocrit (Hct) and % macrocytes were analyzed by logistic regression. One model (ON-model) repeatedly identified 94-100% of r-HuEPO group members during the final 2 wk of the r-HuEPO administration phase. One false positive was recorded from a possible 189. Another model (OFF-model) incorporating RetHct, EPO and Hct was applied during the wash-out phase and, during the period of 12-21 days after the last r-HuEPO injection, it repeatedly identified 67-72% of recent users with no false positives.


CONCLUSIONS
Multiple indirect hematologic and biochemical markers used simultaneously are potentially effective for identifying current or recent users of r-HuEPO.
Parisotto
R
R
Department of Physiology, Australian Institute of Sport, P.O. Box 176, Belconnen ACT 2616, Australia. robin.parisotto@ausport.gov.au.
Gore
C J
CJ
Emslie
K R
KR
Ashenden
M J
MJ
Brugnara
C
C
Howe
C
C
Martin
D T
DT
Trout
G J
GJ
Hahn
A G
AG
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001784:Blood Gas Analysis; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D004300:Doping in Sports / Q000517:prevention & control*; D004311:Double-Blind Method; D004912:Erythrocytes / Q000166:cytology; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood*; D005189:False Positive Reactions; D005260:Female; D005293:Ferritins / Q000097:blood; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000008:administration & dosage; D008297:Male; D011990:Receptors, Transferrin / Q000097:blood; D011994:Recombinant Proteins / Q000097:blood; D012156:Reticulocytes / Q000166:cytology; D019966:Substance-Related Disorders / Q000175:diagnosis*
D015415:Biomarkers; D006454:Hemoglobins; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D004921:Erythropoietin; D005293:Ferritins; D007501:Iron