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* Univariate analysis showed that poor metabolizers had the greatest improvements in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sperm concentration (Figures 1 and 2, p<0.05). There was no statistical difference in testosterone level. Multivariate linear regression indicated that age, clomiphene vs enclomiphene use, baseline hormone levels and sperm concentration were not associated with response (p>0.05), however, metabolizer status significantly predicted increases in LH, FSH, and sperm concentration (p<0.05).
* Infertile men who are poor metabolizers or take strong CYP2D6 inhibitors exhibit greater improvements in gonadotropins and sperm concentration when given enclomiphene therapy. This suggests that decreased clearance of enclomiphene in poor metabolizers leads to prolonged drug circulation and enhanced effects.
GENETIC POLYMORPHISMS OF CYTOCHROME P450 2D6( CYP2D6) ARE ASSOCIATED WITH HORMONAL AND SPERMATOGENIC RESPONSES TO ENCLOMIPHENE THERAPY IN INFERTILE MEN
Taylor P. Kohn*, Blair T. Stocks, Mahdi A. Bazzi, Niki N. Parikh,Mohit Khera, Thomas X. Garcia, Larry I. Lipshultz, Houston, TX
INTRODUCTION AND OBJECTIVE
Clomiphene citrate is a mixture of two isomers, zuclomiphene and enclomiphene. Cytochrome P450 2D6 (CYP2D6) is the primary enzyme that metabolizes various medications; CYP2D6 inactivates enclomiphene. We hypothesize CYP2D6 genotype will predict differential response to clomiphene and enclomiphene among infertile men, with a greater response in those with a “poor metabolizer” variant.
METHODS
We included infertile men at a single institution who received whole genome sequencing and at least six months of clomiphene or enclomiphene therapy. CYP2D6 variants were classified according to PharmVar.org metabolizer phenotypes. Men taking strong CYP2D6 inhibitors (e.g. bupropion, sertraline, fluoxetine) were classified as poor metabolizers.
RESULTS
26 men were included: 10 poor, 5 intermediate, and 11 normal metabolizers. Univariate analysis showed that poor metabolizers had the greatest improvements in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sperm concentration (Figures 1 and 2, p<0.05). There was no statistical difference in testosterone level. Multivariate linear regression indicated that age, clomiphene vs enclomiphene use, baseline hormone levels and sperm concentration were not associated with response (p>0.05), however, metabolizer status significantly predicted increases in LH, FSH, and sperm concentration (p<0.05).
CONCLUSIONS
Infertile men who are poor metabolizers or take strong CYP2D6 inhibitors exhibit greater improvements in gonadotropins and sperm concentration when given enclomiphene therapy. This suggests that decreased clearance of enclomiphene in poor metabolizers leads to prolonged drug circulation and enhanced effects.
* Infertile men who are poor metabolizers or take strong CYP2D6 inhibitors exhibit greater improvements in gonadotropins and sperm concentration when given enclomiphene therapy. This suggests that decreased clearance of enclomiphene in poor metabolizers leads to prolonged drug circulation and enhanced effects.
GENETIC POLYMORPHISMS OF CYTOCHROME P450 2D6( CYP2D6) ARE ASSOCIATED WITH HORMONAL AND SPERMATOGENIC RESPONSES TO ENCLOMIPHENE THERAPY IN INFERTILE MEN
Taylor P. Kohn*, Blair T. Stocks, Mahdi A. Bazzi, Niki N. Parikh,Mohit Khera, Thomas X. Garcia, Larry I. Lipshultz, Houston, TX
INTRODUCTION AND OBJECTIVE
Clomiphene citrate is a mixture of two isomers, zuclomiphene and enclomiphene. Cytochrome P450 2D6 (CYP2D6) is the primary enzyme that metabolizes various medications; CYP2D6 inactivates enclomiphene. We hypothesize CYP2D6 genotype will predict differential response to clomiphene and enclomiphene among infertile men, with a greater response in those with a “poor metabolizer” variant.
METHODS
We included infertile men at a single institution who received whole genome sequencing and at least six months of clomiphene or enclomiphene therapy. CYP2D6 variants were classified according to PharmVar.org metabolizer phenotypes. Men taking strong CYP2D6 inhibitors (e.g. bupropion, sertraline, fluoxetine) were classified as poor metabolizers.
RESULTS
26 men were included: 10 poor, 5 intermediate, and 11 normal metabolizers. Univariate analysis showed that poor metabolizers had the greatest improvements in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sperm concentration (Figures 1 and 2, p<0.05). There was no statistical difference in testosterone level. Multivariate linear regression indicated that age, clomiphene vs enclomiphene use, baseline hormone levels and sperm concentration were not associated with response (p>0.05), however, metabolizer status significantly predicted increases in LH, FSH, and sperm concentration (p<0.05).
CONCLUSIONS
Infertile men who are poor metabolizers or take strong CYP2D6 inhibitors exhibit greater improvements in gonadotropins and sperm concentration when given enclomiphene therapy. This suggests that decreased clearance of enclomiphene in poor metabolizers leads to prolonged drug circulation and enhanced effects.
