Skip to main content
Log in

Tamoxifen is a potent antioxidant modulator for sperm quality in patients with idiopathic oligoasthenospermia

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Objective

To explore the new mechanisms of tamoxifen (TAM) in the treatment for patients with idiopathic oligoasthenospermia—antioxidation.

Methods

In a prospective, randomized, controlled clinical trial, 120 cases of idiopathic oligoasthenospermia were enrolled and randomly assigned to the indomethacin group (n = 60) treated with indomethacin (25 mg, bid) and TAM group (n = 60) treated with TAM (10 mg, bid) for 3 months. Before and after treatment, we evaluated semen parameters, serum malondialdehyde (MDA) and total antioxidant capacity (TAC), seminal plasma MDA and TAC, spermatozoa intracellular reactive oxygen species (ROS), sperm succinate dehydrogenase (SDH) activity, sperm mitochondrial membrane potential (MMP), and sperm adenosine triphosphate (ATP) content. The independent t test and one-way repeated measures analysis of variance were used to compare the variables between and within two groups.

Results

In the indomethacin group, the percentage of progressive motile sperms, total motility, sperm MMP, and ATP content were increased significantly after 3-month treatment (P < 0.05). In the TAM group, total sperm count, sperm concentration, the percentage of progressive motile sperms, total motility, serum and seminal plasma TAC, sperm MMP, and ATP content were significantly improved or increased (P < 0.05), while spermatozoa intracellular ROS was significantly decreased (P < 0.05). Compared to the indomethacin group, TAM treatment showed better improvement in total sperm count, sperm concentration, serum TAC, seminal plasma TAC, spermatozoa intracellular ROS, and sperm SDH activity.

Conclusions

TAM treatment can significantly improve sperm quality, which is achieved through alleviating oxidative stress, improving sperm mitochondrial functionality, and subsequently increasing sperm motility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

TAM:

Tamoxifen

MDA:

Malondialdehyde

TAC:

Total antioxidant capacity

ROS:

Reactive oxygen species

SDH:

Succinate dehydrogenase

MMP:

Mitochondrial membrane potential

ATP:

Adenosine triphosphate

LH:

Luteinizing hormone

FSH:

Follicle-stimulating hormone

TBA:

Thiobarbituric acid

4HNE:

4-Hydroxynonenal

References

  1. Jung JH, Seo JT (2014) Empirical medical therapy in idiopathic male infertility: Promise or panacea? Clin Exp Reprod Med 41(3):108–114

    Article  PubMed Central  PubMed  Google Scholar 

  2. Gudeloglu A, Brahmbhatt JV, Parekattil SJ (2014) Medical management of male infertility in the absence of a specific etiology. Semin Reprod Med 32(4):313–318

    Article  PubMed  Google Scholar 

  3. Hamada AJ, Montgomery B, Agarwal A (2012) Male infertility: a critical review of pharmacologic management. Expert Opin Pharmacother 13(17):2511–2531

    Article  CAS  PubMed  Google Scholar 

  4. Lavranos G, Balla M, Tzortzopoulou A (2012) Investigating ROS sources in male infertility: a common end for numerous pathways. Reprod Toxicol 34(3):298–307

    Article  CAS  PubMed  Google Scholar 

  5. Padron OF, Brackett NL, Sharma RK et al (1997) Seminal reactive oxygen species, sperm motility and morphology in men with spinal cord injury. Fertil Steril 67:1115–1120

    Article  CAS  PubMed  Google Scholar 

  6. Agarwal A, Saleh RA, Bedaiwy MA (2003) Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril 79(4):829–843

    Article  PubMed  Google Scholar 

  7. Ramya T, Misro MM, Sinha D et al (2010) Sperm function and seminal oxidative stress as tools to identify sperm pathologies in infertile men. Fertil Steril 93(1):297–300

    Article  CAS  PubMed  Google Scholar 

  8. Ferramosca A, Pinto Provenzano S, Montagna DD et al (2013) Oxidative stress negatively affects mitochondrial respiration. Urology 82(1):78–83

    Article  PubMed  Google Scholar 

  9. Alvarez JG, Storey BT (1989) Role of glutathione peroxidase in protecting mammalian spermatozoa from loss of motility caused by spontaneous lipid peroxidation. Gamete Res 23:77–90

    Article  CAS  PubMed  Google Scholar 

  10. Nieschlag E, Lenzi A (2013) The conventional management of male infertility. Int J Gynaecol Obstet 123(Suppl 2):S31–S35

    Article  PubMed  Google Scholar 

  11. Ross C, Morriss A, Khairy M et al (2010) A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online 20(6):711–723

    Article  CAS  PubMed  Google Scholar 

  12. Vandekerckhove P, Lilford R, Vail A et al (2000) Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev 2:CD000151

    PubMed  Google Scholar 

  13. Rozati R, Reddy PP, Reddanna P et al (2002) Role of environmental estrogens in the deterioration of male factor fertility. Fertil Steril 78(6):1187–1194

    Article  PubMed  Google Scholar 

  14. Ray A, Shah A, Gudi A et al (2012) Unexplained infertility: an update and review of practice. Reprod Biomed Online 24(6):591–602

    Article  PubMed  Google Scholar 

  15. Chua ME, Escusa KG, 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

    Article  CAS  PubMed  Google Scholar 

  16. Custódio JB, Dinis TC, Almeida LM (1994) Tamoxifen and hydroxytamoxifen as intramembraneous inhibitors of lipid peroxidation. Evidence for peroxyl radical scavenging activity. Biochem Pharmacol 47(11):1989–1998

    Article  PubMed  Google Scholar 

  17. Hernández-Esquivel L, Natalia-Pavón Zazueta C et al (2011) Protection action of tamoxifen on carboxyatractyloside-induced mitochondrial permeability transition. Life Sci 88(15–16):681–687

    Article  PubMed  Google Scholar 

  18. Barkay J, Harpaz-Kerpel S, Ben-Ezra S et al (1984) The prostaglandin inhibitor effect of anti-inflammatory drugs in the therapy of male infertility. Fertil Steril 42(3):406–411

    CAS  PubMed  Google Scholar 

  19. Aydin S, Inci O, Alagöl B (1995) The role of arginine, indomethacin and kallikrein in the treatment of oligoasthenospermia. Int Urol Nephrol 27(2):199–202

    Article  CAS  PubMed  Google Scholar 

  20. Wei Muxin, Yanmin Wu, Chen Dezheng et al (2010) Changes of free radicals and digestive enzymes in saliva in cases with deficiency in spleen-yin syndrome. J Biomed Res 24(3):250–255

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Aitken RJ, Whiting S, De Iuliis GN et al (2012) Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J Biol Chem 287(39):33048–33060

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Salvioli S, Ardizzoni A, Franceschi C et al (1997) JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett 411(1):77–82

    Article  CAS  PubMed  Google Scholar 

  23. Li SF, Liu HX, Zhang YB et al (2010) The protective effects of alpha-ketoacids against oxidative stress on rat spermatozoa in vitro. Asian J Androl 12(2):247–256

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Sigman M, Vance ML (1987) Medical treatment of idiopathic infertility. Urol Clin N Am 14(3):459–469

    CAS  Google Scholar 

  25. Mizrahi R, Breitbart H (2014) Mitochondrial PKA mediates sperm motility. Biochim Biophys Acta 1840(12):3404–3412

    Article  CAS  PubMed  Google Scholar 

  26. Buvat J, Ardacus K, Lemaire A et al (1983) Increased sperm count in 25 cases of idiopathic normozoospermic oligospermia following treatment with tamoxifen. Fertil Steril 39:700–703

    CAS  PubMed  Google Scholar 

  27. Kotoulas IG, Cardamakis E, Michopoulos J et al (1994) Tamoxifen treatment in male infertility. I. Effect of spermatozoa. Fertil Steril 61:911–914

    CAS  PubMed  Google Scholar 

  28. Kamischke A, Nieschlag E (1999) Analysis of medical treatment of male infertility. Hum Reprod 14(Suppl. 1):1–23

    Article  PubMed  Google Scholar 

  29. Benedetti S, Tagliamonte MC, Catalani S et al (2012) Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod Biomed Online 25(3):300–306

    Article  CAS  PubMed  Google Scholar 

  30. Hosseinzadeh Colagar A, Karimi F, Jorsaraei SG (2013) Correlation of sperm parameters with semen lipid peroxidation and total antioxidants levels in astheno- and oligoasheno-teratospermic men. Iran Red Crescent Med J 15(9):780–785

    Article  PubMed Central  PubMed  Google Scholar 

  31. Shamsi MB, Venkatesh S, Kumar R et al (2010) Antioxidant levels in blood and seminal plasma and their impact on sperm parameters in infertile men. Indian J Biochem Biophys 47(1):38–43

    CAS  PubMed  Google Scholar 

  32. Espinoza JA, Schulz MA, Sánchez R et al (2009) Integrity of mitochondrial membrane potential reflects human sperm quality. Andrologia 41(1):51–54

    Article  CAS  PubMed  Google Scholar 

  33. Nadjarzadeh A, Sadeghi MR, Amirjannati N et al (2011) Coenzyme Q10 improves seminal oxidative defense but does not affect on semen parameters in idiopathic oligoasthenoteratozoospermia: a randomized double-blind, placebo controlled trial. J Endocrinol Invest 34(8):e224–e228

    CAS  PubMed  Google Scholar 

  34. Comhaire FH, Christophe AB, Zalata AA et al (2000) The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men. Prostaglandins Leukot Essent Fatty Acids 63:159–165

    Article  CAS  PubMed  Google Scholar 

  35. Tomar R, Mishra AK, Mohanty NK et al (2012) Altered expression of succinic dehydrogenase in asthenozoospermia infertile male. Am J Reprod Immunol 68(6):486–490

    Article  PubMed  Google Scholar 

  36. Wang X, Sharma RK, Gupta A et al (2003) Alterations in mitochondrial membrane potential and oxidative stress in infertile men: a prospective observational study. Fertil Steril 80(Suppl 2):844–850

    Article  PubMed  Google Scholar 

  37. Armstrong JS, Rajasekaran M, Chamulitrat W et al (1999) Characterization of reactive oxygen species induced effects of human spermatozoa movement and energy metabolism. Free Radic Biol Med 26:869–890

    Article  CAS  PubMed  Google Scholar 

  38. Hofmann R, Lehmer A, Gürster E et al (1992) Adenosine triphosphate and adenosine diphosphate in human semen: correlation with sperm count and motility. Urol Int 48(4):391–394

    Article  CAS  PubMed  Google Scholar 

  39. Bilgeri YR, Winchelmann A, Berzin M et al (1987) Adenosine triphosphate levels in human spermatozoa. Arch Androl 18:183

    Article  CAS  PubMed  Google Scholar 

  40. Gerhäuser C, Klimo K, Heiss E et al (2003) Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat Res 523–524:163–172

    Article  PubMed  Google Scholar 

  41. Kamischke A, Nieschlag E (1999) Analysis of medical treatment of male infertility. Hum Reprod 14:1–23

    Article  PubMed  Google Scholar 

  42. Dohle GR, Colpi GM, Hargreave TB et al (2005) EAU guidelines on male infertility. Eur Urol 48(5):703–711

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all the participants for their enthusiastic cooperation, which made this study clinically and scientifically relevant.

Funding

This study was funded by the State Key Development Program for Basic Research of China (Grant No. 2013CB945200).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bing Yao.

Ethics declarations

Conflict of interest

None.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the Declaration of Helsinki 1964 and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Li Guo, Jun Jing, and Yu-Ming Feng have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, L., Jing, J., Feng, YM. et al. Tamoxifen is a potent antioxidant modulator for sperm quality in patients with idiopathic oligoasthenospermia. Int Urol Nephrol 47, 1463–1469 (2015). https://doi.org/10.1007/s11255-015-1065-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-015-1065-2

Keywords

Navigation