| Summary: | Testosterone (T) administration is prohibited in sport by the World Anti-Doping Agency (WADA). Following T administration, both T concentration and the ratio to its inactive stereoisomer, epitestosterone (E), increases. WADA recommends that their accredited laboratories undertake further analysis on urine samples with a T/E greater than 4.0. Acute alcohol consumption (2.0 g/kg) appears to increase this ratio but there is little supporting published data. This thesis describes the testing of different hypotheses based on the influence of alcohol administration on the T/E ratio and attempts to establish the underlying mechanisms. Alcohol was administered to eugonadal men and women (4 and 8 units), and also to hypogonadal men (8 units) receiving T replacement therapy. Hypogonadal men were selected as changes in T would be due solely to altered clearance rather than gonadal production, the data obtained making a useful comparator model. Following alcohol administration, the urinary T/E increased significantly in all the volunteers, in women (8 units) rising from approximately unity to greater than the WADA threshold. Serum analysis showed a decrease in T in males, which indicates that the increase in urinary T/E is most likely due to an increase in the hepatic formation of T glucuronide, which is rapidly excreted, not to an increase in gonadal production. The increase in serum T in females will most likely be due to a suppression of phase 1 metabolism of T, via enzyme inhibition (17 -HSD2), which is likely to also occur in men but is masked by the proportionately much larger concentration of circulating T. There is no evidence that EtOH displaces T from its binding proteins increasing T clearance with a resulting increase in urinary T/E, as tested in vitro by equilibrium dialysis and ultrafiltration, nor is there any evidence that an increase in T/E is due to an increase in lutenising hormone.
|
|---|
