Full Text:   <2574>

Summary:  <1960>

CLC number: R698.2

On-line Access: 2015-03-05

Received: 2014-10-21

Revision Accepted: 2015-01-01

Crosschecked: 2015-02-22

Cited: 2

Clicked: 4960

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Kai-fa Tang

http://orcid.org/0000-0001-7578-0679

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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.3 P.191-197

http://doi.org/10.1631/jzus.B1400282


Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia


Author(s):  Kai-fa Tang, Yi-li Zhao, Shang-shu Ding, Qi-fei Wu, Xing-yang Wang, Jia-qi Shi, Fa Sun, Jun-ping Xing

Affiliation(s):  Department of Urology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China; more

Corresponding email(s):   sfguizhou@163.com, xingjpcn@gmail.com

Key Words:  Infertility, Cytochrome P450, Oligozoospermia, Tamoxifen, Testosterone


Kai-fa Tang, Yi-li Zhao, Shang-shu Ding, Qi-fei Wu, Xing-yang Wang, Jia-qi Shi, Fa Sun, Jun-ping Xing. Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia[J]. Journal of Zhejiang University Science B, 2015, 16(3): 191-197.

@article{title="Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia",
author="Kai-fa Tang, Yi-li Zhao, Shang-shu Ding, Qi-fei Wu, Xing-yang Wang, Jia-qi Shi, Fa Sun, Jun-ping Xing",
journal="Journal of Zhejiang University Science B",
volume="16",
number="3",
pages="191-197",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400282"
}

%0 Journal Article
%T Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia
%A Kai-fa Tang
%A Yi-li Zhao
%A Shang-shu Ding
%A Qi-fei Wu
%A Xing-yang Wang
%A Jia-qi Shi
%A Fa Sun
%A Jun-ping Xing
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 3
%P 191-197
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400282

TY - JOUR
T1 - Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia
A1 - Kai-fa Tang
A1 - Yi-li Zhao
A1 - Shang-shu Ding
A1 - Qi-fei Wu
A1 - Xing-yang Wang
A1 - Jia-qi Shi
A1 - Fa Sun
A1 - Jun-ping Xing
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 3
SP - 191
EP - 197
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400282


Abstract: 
tamoxifen citrate, as the first line of treatment for infertile men with idiopathic oligozoospermia, was proposed by the World Health Organization (WHO), and testosterone undecanoate has shown benefits in semen values. Our objective was to assess the effectiveness of treatment with tamoxifen citrate and testosterone undecanoate in infertile men with idiopathic oligozoospermia, and whether the results would be affected by polymorphisms of CYP2D6*10. A total of 230 infertile men and 147 controls were included in the study. Patients were treated with tamoxifen citrate and testosterone undecanoate. Sex hormone, sperm parameters, and incidence of spontaneous pregnancy were detected. There were no significant differences between the control and patient groups with respect to CYP2D6*10 genotype frequencies (P>0.05). The follicle-stimulation hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were raised, and sperm concentration and motility were increased at 3 months and became significant at 6 months, and they were higher in the wild-type allele (C/C) than in the heterozygous variant allele (C/T) or homozygous variant allele (T/T) subgroups (P<0.05). In addition, the percentage of normal morphology was raised at 6 months, and represented the highest percentage in the C/C subgroup (P<0.05). The incidence of spontaneous pregnancy in the C/C subgroup was higher than that in the C/T or T/T subgroups (P<0.01). This study showed that the CYP2D6*10 variant genotype demonstrated worse clinical effects in infertile men with idiopathic oligozoospermia.

CYP2D6*10基因多态性对他莫昔芬联合十一酸睾酮治疗特发性少精男性不育症的疗效影响

中文概要:
目的:探讨细胞色素P4502D6*10(CYP2D6*10)基因遗传多态性,并评估其对他莫昔芬联合十一酸睾酮治疗特发性少精男性不育症患者血清性激素、精液参数及自然妊娠率的影响。
方法:该病例对照研究包括230例特发性少精男性不育患者和147例正常对照。病例组服用枸橼酸他莫昔芬20mg/d和十一酸睾酮40mg/d,疗程共6个月。采用HphI内切酶对CYP2D6*10基因聚合酶链式反应(PCR)产物进行内切后,从而对其分型。分别于研究开始时、3月及6月分别检测研究对象性激素水平、精液参数及配偶自然妊娠率。
结论: CYP2D6*10基因突变型特发性少精男性不育患者接受他莫昔芬联合十一酸睾酮疗效较基因野生型组差。

关键词:男性不育症;细胞色素P450;少精子症;他莫昔芬;性激素

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Adamopoulos, D.A., Nicopoulou, S., Kapolla, N., et al., 1997. The combination of testosterone undecanoate with tamoxifen citrate enhances the effects of each agent given independently on seminal parameters in men with idiopathic oligozoospermia. Fertil. Steril., 67(4):756-762.

[2]Adamopoulos, D.A., Pappa, A., Billa, E., et al., 2003. Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Fertil. Steril., 80(4):914-920.

[3]Borges, S., Desta, Z., Li, L., et al., 2006. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin. Pharmacol. Ther., 80(1):61-74.

[4]Buvat, J., Ardaens, K., Lemaire, A., et al., 1983. Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen. Fertil. Steril., 39(5):700-703.

[5]Chua, M.E., Escusa, K.G., Luna, S., et al., 2013. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology, 1(5):749-757.

[6]Comhaire, F., 1976. Treatment of oligospermia with tamoxifen. Int. J. Fertil., 21(4):232-238.

[7]Desta, Z., Ward, B.A., Soukhova, N.V., et al., 2004. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J. Pharmacol. Exp. Ther., 310(3):1062-1075.

[8]Garcia-Barcelo, M., Chow, L.Y., Chiu, H.F., et al., 2000. Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population. Clin. Chem., 46(1):18-23.

[9]Ji, L., Pan, S.X., Wu, J.M., et al., 2002a. Genetic polymorphisms of CYP2D6 in Chinese mainland. Chin. Med. J., 115(12):1780-1784.

[10]Ji, L., Pan, S.X., Marti-Jaun, J., et al., 2002b. Single-step assays to analyze CYP2D6 gene polymorphisms in Asians: allele frequencies and a novel *14B allele in mainland Chinese. Clin. Chem., 48(7):983-988.

[11]Jin, Y., Desta, Z., Stearns, V., et al., 2005. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl. Cancer Inst., 97(1):30-39.

[12]Johansson, I., Oscarson, M., Yue, Q.Y., et al., 1994. Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol. Pharmacol., 46(3):452-459.

[13]Kadioglu, T.C., Koksal, I.T., Tunc, M., et al., 1999. Treatment of idiopathic and postvaricocelectomy oligozoospermia with oral tamoxifen citrate. BJU Int., 83(6):646-648.

[14]Kotoulas, I.G., Cardamakis, E., Michopoulos, J., et al., 1994. Tamoxifen treatment in male infertility. I. Effect on spermatozoa. Fertil. Steril., 61(5):911-914.

[15]Lin, C.H., Lien, H.C., Hu, F.C., et al., 2010. Fractionated evaluation of immunohistochemical hormone receptor expression enhances prognostic prediction in breast cancer patients treated with tamoxifen as adjuvant therapy. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 11(1):1-9.

[16]Lu, W.J., Desta, Z., Flockhart, D.A., 2012. Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res. Treat., 131(2):473-481.

[17]Rowe, P.J., Comhaire, F.H., Hargreave, T.B., et al., 2000. WHO Manual for the Standardized Investigation, Diagnosis and Management of the Infertile Male. Cambridge University Press, London, England, p.432-441.

[18]Sachse, C., Brockmoller, J., Bauer, S., et al., 1997. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am. J. Hum. Genet., 60(2):284-295.

[19]Squirewell, E.J., Qin, X., Duffel, M.W., 2014. Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab. Dispos., 42(11):1843-1850.

[20]Stearns, V., Johnson, M.D., Rae, J.M., et al., 2003. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J. Natl. Cancer Inst., 95(23):1758-1764.

[21]Vermeulen, A., Comhaire, F., 1978. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Fertil. Steril., 29(3):320-327.

[22]WHO (World Health Organization), 1999. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interactions, 4th Ed. Cambridge University Press, London, England, p.270-278.

[23]Xu, Y., Sun, Y., Yao, L., et al., 2008. Association between CYP2D6*10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann. Oncol., 19(8):1423-1429.

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