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Abstract Details

Abstract Title

The Impact of Non-Steroidal Aromatase Inhibitors on the Steroid Profile in Chinese

Abstract Theme

Sport medicine and injury prevention

Type Presentation

Oral presentation

Abstract Authors

Presenter Yanyi Xing - China Anti-Doping Agency ( National Anti-doping Laboratory) - CN
Presenter Xin Liu - China Anti-Doping Agency ( National Anti-doping Laboratory) - CN

Presentation Details

Room: Marte        Date: 4 September        Time: 10:00:00        Presenter: Yanyi Xing

Abstract Resume

Background:Aromatase inhibitor is a substance that can suppress the conversion of androgens into estrogens. An increase in the serum testosterone concentration level has been observed
after oral administration of aromatase inhibitor. Therefore, aromatase inhibitors were prohibited by WADA since 2001. Aminoglutethimide, Letrozole and Anastrozole are the most popular non-steroidal
aromatase inhibitors in the market. With the aim to investigate the impact of aromatase inhibitor intake on steroid profile, human subjects of above three drugs were carried out. As a consequence,
some new biomarkers for the evaluation of Athlete Steroid Passport (ASP) were found due to the influence of exogenous substances on the metabolic pathways.

Methods:Six male and six female volunteers received an oral dose (500 mg) of Aminoglutethimide a day and consecutively administered for 3 days. Another two groups of volunteers took
Letrozole (2.5 mg/day) and Anastrozole (1 mg/day) for 5 consecutive days respectively. Urine samples were collected prior 7 days (blank) up to 28 days post administration. 23 biomarkers (steroid
profile concentrations and their ratios) were estimated by GC/MSD. Statistical analyses were performed accordingly.

Results:The graph analysis displayed the concentrations for endogenous androgen biomarkers such as T, ET, AN and ETIO were increased remarkably and the levels of estrogens such as
Estrone, Estradiol and Estriol were decreased notably. The concentrations for all endogenous biomarkers were back to normal within 28 days after administration. T/Estrone, AN/Estrone and ETIO/Estrone
ratios were found to be impacted most significantly by aromatase inhibitor intake employing statistical analyses. Therefore, they could be used as the new biomarkers of ASP for aromatase inhibitor
abuse. In addition, the detection windows for these new biomarkers were more than 20 days after drug administration.
In addition, the negative threshold of above new biomarkers with an appropriate level of confidence (95% and 99% separately) using blank urines was established and these thresholds were utilized to
evaluate samples after aromatase inhibitor administration. By using these thresholds, the suspicious sample rates were increased sharply and displayed as following: 44.41% for male and 55.49% for
female in the level of 95% confidence; 41.62% for male and 41.34% for female in the level of 99% confidence. By contrast, using WADA EAAS TD, the suspicious sample rates were 6.49% for male and 5.4%
for female in the level of 95% confidence; while the rate were 3.64% for male and 1.03% for female in the level of 99% confidence. Therefore, the new biomarkers could be a supplement of ASP evaluation
due to their influence on steroid profile.

Conclusions:Three new biomarkers have been identified to monitor aromatase inhibitor misuse and more suspicious urine samples could be detected. It can probably remedy the limitation
of current WADA EAAS TD. More validations for this new approach are still underway.

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