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Journal Article Observational Study Epublish 2 citations

PubMed: 34690927 DOI: 10.3389/fendo.2021.718917

Could Cytochrome P450 2D6, 3A4 and 3A5 Polymorphisms Explain the Variability in Clinical Response to Clomiphene Citrate of Anovulatory PCOS Women?

Front Endocrinol (Lausanne) 12:718917

Authors: Camille Robin, Benjamin Hennart, Franck Broly, Philippine Gruchala, Geoffroy Robin, Sophie Catteau-Jonard

Affiliations

  • University of Lille, Centre Hospitalier Universitaire (CHU) Lille, Department of Reproductive Medicine, Lille, France.
  • University of Lille, CHU Lille, Service de Toxicologie et Génopathies, Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, Lille, France.
  • University of Lille, CHU Lille, EA 4308 "Gametogenesis and Gamete Quality", Lille, France.
  • University of Lille, CHU Lille, INSERM U1172, Lille, France.

Abstract

Introduction

Cytochrome P450 2D6, 3A4 and 3A5 are involved in the metabolism of many drugs. These enzymes have a genetic polymorphism responsible for different metabolic phenotypes. They play a role in the metabolism of clomiphene citrate (CC), which is used to induce ovulation. Response to CC treatment is variable, and no predictive factors have thus far been identified.

Objective

To study a possible link between the cytochrome P450 2D6, 3A4 and 3A5 polymorphisms and clinical response to CC.

Study Design

Seventy-seven women with anovulatory Polycystic Ovarian Syndrome (PCOS) treated with CC were included which determined their cytochrome P450 2D6, 3A4 and 3A5 genotypes and used the results to predict ovarian response to this drug. Predicted responses based on the cytochrome genotypes were compared with the observed clinical responses using the calculation of a weighted Kappa coefficient.

Main Outcome Measures

Number of dominant follicles assessed by ultrasound at the end of the follicular phase and confirmation of ovulation by blood progesterone assay in the luteal phase.

Results

Concordance between the predicted and observed responses for the combination of the three cytochromes was 36.71%, with a negative Kappa coefficient (K = -0.0240), which corresponds to a major disagreement. Similarly, for predictions based on the cytochrome P450 2D6 genotype alone, only 39.24% of predictions were verified (coefficient K = -0.0609).

Conclusion

The genetic polymorphism of cytochromes P450 2D6, 3A4 and 3A5 does not appear to influence clinical response to CC used to induce ovulation in anovulatory PCOS women.

MeSH

Cytochrome P-450 Enzyme System, Pharmaceutical Preparations, Cytochromes, Cytochrome P-450 Cyp2D6, Polymorphism, Genetic, Genotype, Clomiphene, Ovulation, Endocrine System Diseases, Ovulation Induction