1. Could Cytochrome P450 2D6, 3A4 and 3A5 Polymorphisms Explain the Variability in Clinical Response to Clomiphene Citrate of Anovulatory PCOS Women?
- Author
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Camille Robin, Benjamin Hennart, Franck Broly, Philippine Gruchala, Geoffroy Robin, Sophie Catteau-Jonard, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Lille, Institut Pasteur de Lille, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
- Subjects
Cytochrome ,Pharmacogenomic Variants ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Endocrinology ,Pregnancy ,Follicular phase ,Cytochrome P-450 CYP3A ,polycystic ovary syndrome (PCOS) ,media_common ,Original Research ,biology ,Polycystic ovary syndrome (PCOS) ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Polycystic ovary ,Treatment Outcome ,Cytochrome P-450 CYP2D6 ,Female ,France ,Infertility, Female ,Anovulation ,Polycystic Ovary Syndrome ,Adult ,CYP2D6 ,medicine.medical_specialty ,anti-Müllerian hormone (AMH) ,media_common.quotation_subject ,Luteal phase ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Polymorphism, Single Nucleotide ,Diseases of the endocrine glands. Clinical endocrinology ,Clomiphene ,cytochrome P 450 2D6 ,Young Adult ,Internal medicine ,clomiphene citrate ,medicine ,Humans ,Ovulation ,Genetic Association Studies ,Retrospective Studies ,business.industry ,Fertility Agents, Female ,medicine.disease ,RC648-665 ,biology.protein ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Ovulation induction ,ovulation induction ,business - Abstract
IntroductionCytochrome 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.ObjectiveTo study a possible link between the cytochrome P450 2D6, 3A4 and 3A5 polymorphisms and clinical response to CC.Study DesignSeventy-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 MeasuresNumber 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.ResultsConcordance 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).ConclusionThe 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.
- Published
- 2021