DOI QR코드

DOI QR Code

Misuse of testosterone replacement therapy in men in infertile couples and its influence on infertility treatment

  • Song, Seung-Hun (Department of Urology, Fertility Center, CHA Gangnam Medical Center, CHA University) ;
  • Sung, Suye (Fertility Center of CHA Gangnam Medical Center) ;
  • Her, Young Sun (Fertility Center of CHA Gangnam Medical Center) ;
  • Oh, Mihee (Fertility Center of CHA Gangnam Medical Center) ;
  • Shin, Dong Hyuk (Fertility Center of CHA Gangnam Medical Center) ;
  • Lee, Jinil (Fertility Center of CHA Gangnam Medical Center) ;
  • Baek, Jeongwon (Fertility Center of CHA Gangnam Medical Center) ;
  • Lee, Woo Sik (Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University) ;
  • Kim, Dong Suk (Department of Urology, Fertility Center, CHA Gangnam Medical Center, CHA University)
  • Received : 2019.05.31
  • Accepted : 2019.08.01
  • Published : 2019.12.31

Abstract

Objective: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples. Methods: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (< 5 × 106/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded. Results: The mean age of patients was 37 years and the mean duration of infertility was 16.3 ± 11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months. Conclusion: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.

Keywords

References

  1. Corona G, Sforza A, Maggi M. Testosterone replacement therapy: long-term safety and efficacy. World J Mens Health 2017;35:65-76. https://doi.org/10.5534/wjmh.2017.35.2.65
  2. Layton JB, Li D, Meier CR, Sharpless JL, Sturmer T, Jick SS, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Clin Endocrinol Metab 2014;99:835-42. https://doi.org/10.1210/jc.2013-3570
  3. Handelsman DJ. Global trends in testosterone prescribing, 2000-2011: expanding the spectrum of prescription drug misuse. Med J Aust 2013;199:548-51. https://doi.org/10.5694/mja13.10111
  4. O'Brien JH, Lazarou S, Deane L, Jarvi K, Zini A. Erectile dysfunction and andropause symptoms in infertile men. J Urol 2005;174:1932-4. https://doi.org/10.1097/01.ju.0000177453.14334.a2
  5. Traish A. Testosterone therapy in men with testosterone deficiency: are we beyond the point of no return? Investig Clin Urol 2016;57:384-400. https://doi.org/10.4111/icu.2016.57.6.384
  6. Patel AS, Leong JY, Ramos L, Ramasamy R. Testosterone is a contraceptive and should not be used in men who desire fertility. World J Mens Health 2019;37:45-54. https://doi.org/10.5534/wjmh.180036
  7. Kolettis PN, Purcell ML, Parker W, Poston T, Nangia AK. Medical testosterone: an iatrogenic cause of male infertility and a growing problem. Urology 2015;85:1068-73. https://doi.org/10.1016/j.urology.2014.12.052
  8. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010.
  9. Madill JJ, Mullen NB, Harrison BP. Ovarian hyperstimulation syndrome: a potentially fatal complication of early pregnancy. J Emerg Med 2008;35:283-6. https://doi.org/10.1016/j.jemermed.2007.11.074
  10. Han AR, Kim HO, Cha SW, Park CW, Kim JY, Yang KM, et al. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study. Clin Exp Reprod Med 2011;38:103-8. https://doi.org/10.5653/cerm.2011.38.2.103
  11. Song SH, Kim DS, Yoon TK, Hong JY, Shim SH. Sexual function and stress level of male partners of infertile couples during the fertile period. BJU Int 2016;117:173-6. https://doi.org/10.1111/bju.13201
  12. Bang JK, Lim JJ, Choi J, Won HJ, Yoon TK, Hong JY, et al. Reversible infertility associated with testosterone therapy for symptomatic hypogonadism in infertile couple. Yonsei Med J 2013;702-6. https://doi.org/10.3349/ymj.2013.54.3.702
  13. Ly LP, Liu PY, Handelsman DJ. Rates of suppression and recovery of human sperm output in testosterone-based hormonal contraceptive regimens. Hum Reprod 2005;20:1733-40. https://doi.org/10.1093/humrep/deh834
  14. Ko EY, Siddiqi K, Brannigan RE, Sabanegh ES Jr. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol 2012;187:973-8. https://doi.org/10.1016/j.juro.2011.10.137
  15. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C; Hormonal Male Contraception Summit Group. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 2006;367:1412-20. https://doi.org/10.1016/S0140-6736(06)68614-5
  16. Kohn TP, Louis MR, Pickett SM, Lindgren MC, Kohn JR, Pastuszak AW, et al. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril 2017;107:351-7. https://doi.org/10.1016/j.fertnstert.2016.10.004
  17. McBride JA, Coward RM. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian J Androl 2016;18:373-80. https://doi.org/10.4103/1008-682X.173938
  18. Coward RM, Simhan J, Carson CC 3rd. Prostate-specific antigen changes and prostate cancer in hypogonadal men treated with testosterone replacement therapy. BJU Int 2009;103:1179-83. https://doi.org/10.1111/j.1464-410X.2008.08240.x
  19. Tan RS, Salazar JA. Risks of testosterone replacement therapy in ageing men. Expert Opin Drug Saf 2004;3:599-606. https://doi.org/10.1517/14740338.3.6.599
  20. Elsherbiny A, Tricomi M, Bhatt D, Dandapantula HK. State-of-theart: a review of cardiovascular effects of testosterone replacement therapy in adult males. Curr Cardiol Rep 2017;19:35. https://doi.org/10.1007/s11886-017-0838-x