Dose-response effect of alcohol ingestion on steroid profile: Gender and ethnic aspects (acronym: profethyl2)

Code: 15D09RT 

The introduction of the so called ‘endocrine module’ of the athlete’s biological passport needs to consider the numerous reports showing the effect of ethanol ingestion on the steroid profile. A steroid profile would only be useful for longitudinal monitoring and statistical evaluation if it has not been altered by any uncontrolled circumstance, very particularly alcohol consumption. Preliminary results (Profethyl project) in male Caucasian show that moderate doses of ethanol alter very fast T/E values and variations account for more than 70% change in T/E value that would have triggered a confirmation and IRMS analysis. 
Interethnic studies on the T/E ratio have already shown the difficulty in establishing a single threshold value applicable to all ethnicities to evidence testosterone misuse. Asian athletes are those with the lowest mean T/E ratio. This in part is due to the larger prevalence of the deletion polymorphism in the UGT2B17 gene in Asian population that regulates testosterone glucuronidation. Previous studies were performed in male Caucasian healthy volunteers. Alterations seen in males after moderate ethanol consumption should be replicated in women since it is expected that they will be larger because typically display milder first pass metabolism and lower T and E concentrations. 
The main objective of the project is to study the intra-individual variation of steroid profile parameters as a result of the ingestion of low doses of ethanol in Caucasian and Chinese males (20 and 40 gr of ethanol) and females (10 and 20 gr of ethanol), being the UGT2B17 polymorphism evaluated as covariate. 

Main Findings: 

The objective of the project is to study the intra-individual variation of steroid profile parameters as a result of the ingestion of low doses of ethanol, compatible with a mild social consumption habit without achieving states of acute intoxication. The study was performed in Caucasian as well as Asian subjects to evaluate the inter-ethnic and or genotypic differences.
In this context 12 Caucasian and 12 Chinese women were administered 10 g (0.7 times of a US standard drink of 14 g, USD) and 20 g (1.4 USD) of alcohol (in the form a vodka based drink). In the same study 12 Chinese male subjects were administered with 20 g (1.4 USD but only 70% of the daily dose recommended in males) and 40 g (2.85 USD but 140% of the daily dose recommended in males).
The main findings regarding the monitoring of alcohol biomarkers, ethyl glucuronide (EtG) and ethyl sulfate (EtS) were as follows:
- Both EtG and EtS are good biomarkers of alcohol consumption. They are excreted in equimolar amounts. Ethyl sulfate seems a more suitable marker since its artefactual formation due to urine bacterial contamination has not been reported and its kinetics of excretion, depending on the population might better fit the changes observed in the steroid profile.
- There are gender differences being males that excrete more EtG and EtS than females (about 2 times more) independently of ethnicity.
- EtS precedes kinetically to EtG in Caucasian populations, while both kinetics showed to be superimposable in Chinese subjects.
- Caucasian subjects excreted 5 times more EtG ad EtS and had higher blood alcohol concentrations than Chinese subjects.
·    This is the first time that interethnic differences in biomarkers of alcohol consumption are reported.
·    Interethnic differences have to be considered if never cut-off concentrations in the context of the biological passport would be established.
The Main findings regarding ethanol induced alterations in the steroid profile
- The ratios 5αADiol/E and 5βADiol/E compared to T/E and 100·T/A ratios are more sensitive to alterations induced by moderate doses of alcohol
- Alterations in the steroid profile are more marked in Caucasian subjects than in Chinese subjects carrying functional/partially functional genotypes for the UGT2B17enzyme.
- Regarding genetics of the UGT2B17, globally in carriers of the non-functional genotype minor if any alterations after alcohol intake are observed
·    In Chinese male subjects where 11 over 12 carry a non-functional genotype for the UGT2B17 polymorphism no alterations in the T/E and T/A ratios are observed, while minor changes are observed in the ratios 5αADiol/E and 5βADiol/E
·    In Chinese female subjects where there are 3 of them carrying partially non-functional genotypes, changes observed are more marked as compared with carriers of non-functional genotypes.
·    In Caucasian females subjects where 11 over 12 carry genotypes mostly functional and in some cases partially functional, ethanol induces alterations in the steroid profile.