Effect of CYP2D6*10 (100C > T) Polymorphisms on Clomiphene Citrate Response in Iraqi Women with PCOS

Abstract

Background

Clomiphene citrate (CC) is a commonly prescribed drug to induce ovulation in women with PCOS, a hormonal disorder affecting women of reproductive age. The CYP2D6 is an enzyme vital in metabolizing CC to its active metabolite. Variations in this gene, such as CYP2D6*10, which reduces enzyme activity, can affect drug metabolism and potentially impact treatment outcomes.

Materials and Methods

The cohort study, conducted from September 2023 to April 2024, enrolled 80 women diagnosed with PCOS. All patients received 100mg/day of CC from cycle day 2 for at least 2 cycles. Whole blood was collected for hormonal assays and CYP2D6*10 genotyping by ARMS PCR. Furthermore, an ultrasound was performed to determine follicle size and endometrial thickness during the cycle.

Results

We found that the frequency of CYP2D6*10 genotypes is 66.3% (CC), 27.5% (CT), and 6.3% (TT). Women with the mutant allele exhibited significantly lower concentrations of the active metabolite and higher concentrations of the prodrug (p < 0.05). At the same time, the CT genotype showed a higher AMH level.

Conclusions                   

Our findings prove an association between the CYP2D6*10 genotype and CC metabolism. However, further research with a larger sample size to confirm these findings. Additionally, an assessment of AMH level may also help predict CC.