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Sex-specific UGT expression and function: prevalence, potential mechanisms and significance
Robyn Meech1, Dong Gui Hu1, Julie-Ann Hulin1
1Discipline of Pharmacology, College of Medicine and Public Health, Flinders Health and Medical Research Institution (FHMRI), Flinders University, Bedford Park, Adelaide, Australia.
Expert Opinion on Drug Metabolism & Toxicology
|March 13, 2025
Summary
Sex differences in drug metabolism, particularly involving UDP-glucuronosyltransferases (UGTs), impact drug exposure and outcomes. More research is needed to understand and address these sex-based variations in pharmacotherapy.
Area of Science:
- Pharmacology
- Drug Metabolism
- Sex Differences in Medicine
Background:
- Adverse drug effects are nearly twice as common in women.
- Sex and gender influence pharmacotherapy outcomes due to variations in body composition, physiology, and prescribing patterns.
- Many drugs exhibit higher exposure in women, linked to sex-differences in drug disposition processes like metabolism and transport.
Purpose of the Study:
- To review sex differences in the expression and function of UDP-glucuronosyltransferases (UGTs).
- To curate literature on sex-biased UGT expression in human tissues.
- To evaluate the contribution of UGTs to sex-differences in drug exposure and clinical outcomes.
Main Methods:
- Literature search of PubMed using terms related to UGTs, glucuronidation, sex, and gender.
- Curated literature on sex-biased UGT expression and function.
- Critically evaluated evidence for UGT-mediated sex-differences in drug outcomes.
Main Results:
- Identified several examples of sex-biased UGT expression and drug glucuronidation.
- Limited evidence was found for a significant clinical impact of these sex differences.
- Significant data gaps exist in understanding the prevalence and importance of sex-biased glucuronidation.
Conclusions:
- While sex-biased UGT expression and glucuronidation exist, their clinical significance is not fully established.
- Further research using novel methodologies and sex-aware data analysis is crucial.
- Addressing these gaps can lead to improved pharmacotherapy for all genders.
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