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Non-steroidal anti-inflammatory drugs interact with testosterone glucuronidation
Taina Sten1, Moshe Finel, Birgitta Ask
1Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Steroids
|August 1, 2009
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and diclofenac can interfere with testosterone glucuronidation, potentially impacting doping tests. UGT2B15 is more sensitive to these NSAIDs than UGT2B17.
Area of Science:
- Pharmacology
- Biochemistry
- Sports Science
Background:
- The urinary testosterone to epitestosterone ratio (T/E) is a key marker for detecting anabolic steroid abuse in athletes.
- UDP-glucuronosyltransferase (UGT) 2B17 is the primary enzyme responsible for testosterone glucuronidation, forming the basis of the T/E ratio.
- The T/E ratio can be influenced by drugs that interact with UGT enzymes involved in testosterone metabolism.
Purpose of the Study:
- To investigate the effects of common non-steroidal anti-inflammatory drugs (NSAIDs), specifically diclofenac and ibuprofen, on testosterone and epitestosterone glucuronidation.
- To determine the inhibitory potential of these NSAIDs on key UGT enzymes, including UGT2B17 and UGT2B15.
- To assess the implications of these interactions for the accuracy of anti-doping tests.
Main Methods:
- Examined the glucuronidation of testosterone and epitestosterone in human liver microsomes incubated with diclofenac and ibuprofen.
- Assessed the inhibitory effects of diclofenac and ibuprofen on recombinant UGT2B17, UGT2B15, and other relevant human hepatic UGTs (UGT1A3, UGT1A4, UGT1A9, UGT2B7).
- Utilized human liver microsomes deficient in UGT2B17 to evaluate the role of UGT2B15 in residual testosterone glucuronidation.
Main Results:
- Both diclofenac and ibuprofen significantly inhibited testosterone glucuronidation in human liver microsomes.
- These NSAIDs demonstrated inhibitory effects on both UGT2B17 and UGT2B15, with UGT2B15 showing greater sensitivity, particularly to ibuprofen.
- Epitestosterone glucuronidation was largely unaffected by ibuprofen and diclofenac in human liver microsomes.
- UGT2B15 appears to play a significant role in testosterone glucuronidation in UGT2B17-deficient individuals, with a potential minor contribution from UGT1A9.
Conclusions:
- NSAIDs like diclofenac and ibuprofen can interfere with testosterone glucuronidation pathways mediated by UGT enzymes.
- The differential sensitivity of UGT2B15 and UGT2B17 to NSAIDs suggests a complex interaction that could potentially affect the interpretation of T/E ratio doping tests.
- Further research is warranted to fully elucidate the clinical implications of NSAID use on androgen metabolism and anti-doping strategies.
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