Biology Reference
In-Depth Information
offer some protection against the known side-effects in patients with anemia;
however, athletes are deliberately increasing their hematocrits to levels associ-
ated with thromboembolic and other complications. Despite the increases,
only one case has been reported that appears to link rHuEPO to a cerebral
thrombosis. The athlete admitted to using rHuEPO and other drugs [43].
Athletes who use rHuEPO are at risk of developing true iron deficiency, func-
tional iron deficiency, or iron overload. Of course, careful professional med-
ical management could avoid these complications. Cazzola reports that an
investigation by Italian magistrates [44] reveals that some professional cyclists
have evidence of iron overload with ferritin levels in excess of 1,000 ng/mL
[45]. The investigation also provided data consistent with a risk of post-treat-
ment blunted production of endogenous EPO [45]. In addition Berglund and
Ekblom [42] have studied the effect of rHuEPO on the blood pressure of ath-
letes. The systolic and diastolic blood pressure values at rest were unchanged
after rHuEPO treatment; however, systolic blood pressure markedly increased
during submaximal exercise. The initial and final values were 177 mmHg and
191 mmHg, respectively [42]. The propensity of athletes to titrate their hema-
tocrits to high levels and to take rHuEPO without adequate medical supervi-
sion, together with their risk for iron disorders and exercise-induced increased
systolic pressure, make it likely that more adverse effects are occurring than
are reported in the medical literature. This under-reporting is inherent to the
secretive nature of doping.
Detecting erythropoietic proteins in body fluids
Direct and indirect tests
Sport classifies tests for doping substances as direct or indirect. A direct test
identifies the substance by an unambiguous method such as gas chromatogra-
phy-mass spectrometry, whereas indirect tests measure, for example, the
serum concentration of markers that correlate with the use of a prohibited sub-
stance, without directly identifying the substance. Direct tests sufficed for
many years, but now that doping includes endogenous steroids and glycopro-
teins, a variety of new strategies and indirect tests have been developed [46].
Indirect tests have not been used to declare that an athlete has used a sub-
stance, but it is hoped that with sufficient validation, these tests could become
definitive.
Detecting the use of pharmaceutical testosterone was a challenge with gas
chromatography-mass spectrometry because pharmaceutical and endogenous
testosterone could not be distinguished. The problem was partly solved by per-
forming longitudinal tests of the urinary steroid profile and by determining the
13
C/
12
C ratio of urinary testosterone by isotope ratio mass spectrometry [47].
The glycoproteins present a special challenge because, to date, it has not been
practical to develop a mass spectrometry-based method that is sensitive
