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  • Review Article
  • Published:

Adverse effects of common medications on male fertility

Nature Reviews Urology volume 12, pages 401–413 (2015)Cite this article

Subjects

Key Points

  • Many medications used in urology can have effects on male reproduction that are generally reversible; however, studies in humans are limited and men should be counselled appropriately

  • Exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic–pituitary–gonadal hormonal axis

  • 5α-reductase inhibitors can affect sexual function, decrease semen volume and alter sperm parameters; α-blockers decrease seminal emission and cause retrograde ejaculation, dependent on receptor specificity of the agent and its dose

  • Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited, and study results are conflicting

  • Antihypertensive and psychotropic agents affect semen parameters, sexual function and hormonal parameters; for antibiotics, the literature on effects on sperm and sperm function is limited and dated

  • Many chemotherapeutic agents have a direct gonadotoxic effect, dependent on agents used, dosing and number of treatment cycles

Abstract

An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic–pituitary–gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

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References

  1. Martinez, G., Daniels, K. & Chandra, A. Fertility of men and women aged 15–44 years in the United States: National Survey of Family Growth, 2006–2010. Natl Health Stat. Report 12, 1–28 (2012).

    Google Scholar 

  2. Kaufman, D. W., Kelly, J. P., Rosenberg, L., Anderson, T. E. & Mitchell, A. A. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 287, 337–344 (2002).

    Article  PubMed  Google Scholar 

  3. Cox, E. R., Halloran, D. R., Homan, S. M., Welliver, S. & Mager, D. E. Trends in the prevalence of chronic medication use in children: 2002–2005. Pediatrics 122, e1053–e1061 (2008).

    Article  PubMed  Google Scholar 

  4. U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for industry. Reproductive and developmental toxicities—integrating study results to assess concerns [online], (2011).

  5. Alonso, V. et al. Sulfasalazine induced oxidative stress: a possible mechanism of male infertility. Reprod. Toxicol. 27, 35–40 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Johnson, L., Petty, C. S. & Neaves, W. B. A comparative study of daily sperm production and testicular composition in humans and rats. Biol. Reprod. 22, 1233–1243 (1980).

    Article  CAS  PubMed  Google Scholar 

  7. Handelsman, D. J. Pharmacoepidemiology of testosterone prescribing in Australia, 1992–2010. Med. J. Aust. 196, 642–645 (2012).

    Article  PubMed  Google Scholar 

  8. Gan, E. H., Pattman, S., Pearce, S. H. & Quinton, R. A UK epidemic of testosterone prescribing, 2001–2010. Clin. Endocrinol. (Oxf.) 79, 564–570 (2013).

    Article  Google Scholar 

  9. Baillargeon, J., Urban, R. J., Ottenbacher, K. J., Pierson, K. S. & Goodwin, J. S. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern. Med. 173, 1465–1466 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Layton, J. B. et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J. Clin. Endocrinol. Metab. 99, 835–842 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gonzalo, I. T. et al. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J. Clin. Endocrinol. Metab. 87, 3562–3572 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Ko, E. Y., Siddiqi, K., Brannigan, R. E. & Sabanegh, E. S. Jr. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J. Urol. 187, 973–978 (2012).

    Article  PubMed  Google Scholar 

  13. Kolettis, P. N., Purcell, M. L., Parker, W., Poston, T. & Nangia, A. K. Medical testosterone: an iatrogenic cause of male infertility and a growing problem. Urology 85, 1068–1073 (2015).

    Article  PubMed  Google Scholar 

  14. Samplaski, M. K. et al. Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters. Fertil. Steril. 101, 64–69 (2014).

    Article  CAS  PubMed  Google Scholar 

  15. Gu, Y. et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J. Clin. Endocrinol. Metab. 94, 1910–1915 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Liu, P. Y. et al. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 367, 1412–1420 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Rahnema, C. D., Lipshultz, L. I., Crosnoe, L. E., Kovac, J. R. & Kim, E. D. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil. Steril. 101, 1271–1279 (2014).

    Article  CAS  PubMed  Google Scholar 

  18. Kim, E. D., Crosnoe, L., Bar-Chama, N., Khera, M. & Lipshultz, L. I. The treatment of hypogonadism in men of reproductive age. Fertil. Steril. 99, 718–724 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. Eaton, D. K. et al. Youth risk behavior surveillance—United States, 2011. MMWR Surveill. Summ. 61, 1–162 (2012).

    PubMed  Google Scholar 

  20. Ito, T. & Horton, R. The source of plasma dihydrotestosterone in man. J. Clin. Invest. 50, 1621–1627 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. McConnell, J. D. et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N. Engl. J. Med. 338, 557–563 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Nepple, K. G. & Andriole, G. L. Prostate cancer chemoprevention with 5α-reductase inhibitors. Urol. Oncol. 30, 553–554 (2012).

    Article  PubMed  Google Scholar 

  23. Jenkins, E. P., Andersson, S., Imperato-McGinley, J., Wilson, J. D. & Russell, D. W. Genetic and pharmacological evidence for more than one human steroid 5 α reductase. J. Clin. Invest. 89, 293–300 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Clark, R. V. et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5α reductase inhibitor. J. Clin. Endocrinol. Metab. 89, 2179–2184 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Gormley, G. J. et al. The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N. Engl. J. Med. 327, 1185–1191 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Rittmaster, R. S. et al. Effect of finasteride, a 5α reductase inhibitor, on serum gonadotropins in normal men. J. Clin. Endocrinol. Metab. 75, 484–488 (1992).

    CAS  PubMed  Google Scholar 

  27. Amory, J. K. et al. The effect of 5α reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J. Clin. Endocrinol. Metab. 92, 1659–1665 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Overstreet, J. W. et al. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. J. Urol. 162, 1295–1300 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Samplaski, M. K., Lo, K., Grober, E. & Jarvi, K. Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertil. Steril. 100, 1542–1546 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Tu, H. Y. & Zini, A. Finasteride-induced secondary infertility associated with sperm DNA damage. Fertil. Steril. 95, 2125.e13–2125.e14 (2011).

    Article  Google Scholar 

  31. Gur, S., Kadowitz, P. J. & Hellstrom, W. J. Effects of 5α reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin. Drug Saf. 12, 81–90 (2013).

    Article  CAS  PubMed  Google Scholar 

  32. Traish, A. M., Hassani, J., Guay, A. T., Zitzmann, M. & Hansen, M. L. Adverse side effects of 5α reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J. Sex. Med. 8, 872–884 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Irwig, M. S. & Kolukula, S. Persistent sexual side effects of finasteride for male pattern hair loss. J. Sex. Med. 8, 1747–1753 (2011).

    Article  PubMed  Google Scholar 

  34. Shindel, A. W., Nelson, C. J., Naughton, C. K., Ohebshalom, M. & Mulhall, J. P. Sexual function and quality of life in the male partner of infertile couples: prevalence and correlates of dysfunction. J. Urol. 179, 1056–1059 (2008).

    Article  PubMed  Google Scholar 

  35. Spritzer, M. D. & Galea, L. A. Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Dev. Neurobiol. 67, 1321–1333 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Caruso, D. et al. Comparison of plasma and cerebrospinal fluid levels of neuroactive steroids with their brain, spinal cord and peripheral nerve levels in male and female rats. Psychoneuroendocrinology 38, 2278–2290 (2013).

    Article  CAS  PubMed  Google Scholar 

  37. Kaufman, K. D. et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J. Am. Acad. Dermatol. 39, 578–589 (1998).

    Article  CAS  PubMed  Google Scholar 

  38. McClellan, K. J. & Markham, A. Finasteride: a review of its use in male pattern hair loss. Drugs 57, 111–126 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Wessells, H. et al. Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology 61, 579–584 (2003).

    Article  PubMed  Google Scholar 

  40. Byrnes, C. A., Morton, A. S., Liss, C. L., Lippert, M. C. & Gillenwater, J. Y. Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar. Clin. Ther. 17, 956–969 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Nickel, J. C. et al. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2 year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study. CMAJ 155, 1251–1259 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lowe, F. C. et al. Long-term 6 year experience with finasteride in patients with benign prostatic hyperplasia. Urology 61, 791–796 (2003).

    Article  PubMed  Google Scholar 

  43. Mondaini, N. et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? J. Sex. Med. 4, 1708–1712 (2007).

    Article  PubMed  Google Scholar 

  44. Debruyne, F. et al. Efficacy and safety of long-term treatment with the dual 5 α reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur. Urol. 46, 488–494; discussion 495 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Roehrborn, C. G. et al. Efficacy and safety of a dual inhibitor of 5 α reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 60, 434–441 (2002).

    Article  PubMed  Google Scholar 

  46. Furukawa, K. et al. α 1A adrenoceptor mediated contractile responses of the human vas deferens. Br. J. Pharmacol. 116, 1605–1610 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tambaro, S. et al. Evaluation of tamsulosin and alfuzosin activity in the rat vas deferens: relevance to ejaculation delays. J. Pharmacol. Exp. Ther. 312, 710–717 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Hisasue, S. et al. Ejaculatory disorder caused by α1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission. Int. J. Urol. 13, 1311–1316 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Hellstrom, W. J. & Sikka, S. C. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J. Urol. 176, 1529–1533 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Andersson, K. E. & Gratzke, C. Pharmacology of α1 adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat. Clin. Pract. Urol. 4, 368–378 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Gacci, M. et al. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review and meta-analysis. J. Sex. Med. 11, 1554–1566 (2014).

    Article  CAS  PubMed  Google Scholar 

  52. Kaplan, S. A. Side effects of α blocker use: retrograde ejaculation. Rev. Urol. 11 (Suppl. 1), S14–S18 (2009).

    PubMed  PubMed Central  Google Scholar 

  53. Chen, Y., Li, H., Dong, Q. & Wang, K. J. Blockade of α1A adrenoceptor: a novel possible strategy for male contraception. Med. Hypotheses 73, 140–141 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Lepor, H., Kazzazi, A. & Djavan, B. α Blockers for benign prostatic hyperplasia: the new era. Curr. Opin. Urol. 22, 7–15 (2012).

    Article  PubMed  Google Scholar 

  55. Roehrborn, C. G. et al. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2 year results from the CombAT study. J. Urol. 179, 616–621; discussion 621 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. Hellstrom, W. J. & Sikka, S. C. Effects of alfuzosin and tamsulosin on sperm parameters in healthy men: results of a short-term, randomized, double-blind, placebo-controlled, crossover study. J. Androl. 30, 469–474 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Sinclair, M. L. et al. Specific expression of soluble adenylyl cyclase in male germ cells. Mol. Reprod. Dev. 56, 6–11 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Fisch, J. D., Behr, B. & Conti, M. Enhancement of motility and acrosome reaction in human spermatozoa: differential activation by type-specific phosphodiesterase inhibitors. Hum. Reprod. 13, 1248–1254 (1998).

    Article  CAS  PubMed  Google Scholar 

  59. Su, Y. H. & Vacquier, V. D. Cyclic GMP-specific phosphodiesterase 5 regulates motility of sea urchin spermatozoa. Mol. Biol. Cell 17, 114–121 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Glenn, D. R., McVicar, C. M., McClure, N. & Lewis, S. E. Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. Fertil. Steril. 87, 1064–1070 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Fawcett, L. et al. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc. Natl Acad. Sci. USA 97, 3702–3707 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Makhlouf, A., Kshirsagar, A. & Niederberger, C. Phosphodiesterase 11: a brief review of structure, expression and function. Int. J. Impot. Res. 18, 501–509 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Wayman, C. et al. Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology. Int. J. Impot. Res. 17, 216–223 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. du Plessis, S. S., de Jongh, P. S. & Franken, D. R. Effect of acute in vivo sildenafil citrate and in vitro 8 bromo cGMP treatments on semen parameters and sperm function. Fertil. Steril. 81, 1026–1033 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Lefièvre, L., De Lamirande, E. & Gagnon, C. The cyclic GMP-specific phosphodiesterase inhibitor, sildenafil, stimulates human sperm motility and capacitation but not acrosome reaction. J. Androl. 21, 929–937 (2000).

    PubMed  Google Scholar 

  66. Burger, M., Sikka, S. C., Bivalacqua, T. J., Lamb, D. J. & Hellstrom, W. J. The effect of sildenafil on human sperm motion and function from normal and infertile men. Int. J. Impot. Res. 12, 229–234 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Purvis, K., Muirhead, G. J. & Harness, J. A. The effects of sildenafil on human sperm function in healthy volunteers. Br. J. Clin. Pharmacol. 53 (Suppl. 1), 53S–60S (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Aversa, A. et al. Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum. Reprod. 15, 131–134 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Jannini, E. A., Lombardo, F., Salacone, P., Gandini, L. & Lenzi, A. Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate. Fertil. Steril. 81, 705–707 (2004).

    Article  CAS  PubMed  Google Scholar 

  70. Jarvi, K. et al. Daily vardenafil for 6 months has no detrimental effects on semen characteristics or reproductive hormones in men with normal baseline levels. J. Urol. 179, 1060–1065 (2008).

    Article  PubMed  Google Scholar 

  71. Sousa, M. I., Amaral, S., Tavares, R. S., Paiva, C. & Ramalho-Santos, J. Concentration-dependent sildenafil citrate (Viagra) effects on ROS production, energy status, and human sperm function. Syst. Biol. Reprod. Med. 60, 72–79 (2014).

    Article  CAS  PubMed  Google Scholar 

  72. Yang, Y. et al. Effect of acute tadalafil on sperm motility and acrosome reaction: in vitro and in vivo studies. Andrologia 46, 417–422 (2014).

    Article  CAS  PubMed  Google Scholar 

  73. Lilly USA, LLC. Highlights of prescribing information. CIALIS (tadalafil) tablets, for oral use [online], (2014).

  74. Hellstrom, W. J. et al. Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones. J. Urol. 170, 887–891 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Pomara, G. et al. Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. Fertil. Steril. 88, 860–865 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. Nudell, D. M., Monoski, M. M. & Lipshultz, L. I. Common medications and drugs: how they affect male fertility. Urol. Clin. North Am. 29, 965–973 (2002).

    Article  PubMed  Google Scholar 

  77. Carter, M. D., Hollander, M. B. & Lipshultz, L. I. In the medicine cabinet, clues to infertility. Contemp. Urol. 5, 51–63 (1993).

    Google Scholar 

  78. Hendrick, V., Gitlin, M., Altshuler, L. & Korenman, S. Antidepressant medications, mood and male fertility. Psychoneuroendocrinology 25, 37–51 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Montejo, A. L., Llorca, G., Izquierdo, J. A. & Rico-Villademoros, F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J. Clin. Psychiatry 62 (Suppl. 3), 10–21 (2001).

    CAS  PubMed  Google Scholar 

  80. Kumar, V. S. et al. The spermicidal and antitrichomonas activities of SSRI antidepressants. Bioorg. Med. Chem. Lett. 16, 2509–2512 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Tanrikut, C. & Schlegel, P. N. Antidepressant-associated changes in semen parameters. Urology 69, 185.e5–185.e7 (2007).

    Article  Google Scholar 

  82. Safarinejad, M. R. Sperm DNA damage and semen quality impairment after treatment with selective serotonin reuptake inhibitors detected using semen analysis and sperm chromatin structure assay. J. Urol. 180, 2124–2128 (2008).

    Article  PubMed  Google Scholar 

  83. Tanrikut, C., Feldman, A. S., Altemus, M., Paduch, D. A. & Schlegel, P. N. Adverse effect of paroxetine on sperm. Fertil. Steril. 94, 1021–1026 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Maier, U. & Koinig, G. Andrological findings in young patients under long-term antidepressive therapy with clomipramine. Psychopharmacology (Berl.) 116, 357–359 (1994).

    Article  CAS  Google Scholar 

  85. Levin, R. M., Amsterdam, J. D., Winokur, A. & Wein, A. J. Effects of psychotropic drugs on human sperm motility. Fertil. Steril. 36, 503–506 (1981).

    Article  CAS  PubMed  Google Scholar 

  86. Wilson, B. The effect of drugs on male sexual function and fertility. Nurse Pract. 16, 12–17, 21–24 (1991).

    CAS  PubMed  Google Scholar 

  87. Serretti, A. & Chiesa, A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin. Pharmacol. Ther. 89, 142–147 (2011).

    Article  CAS  PubMed  Google Scholar 

  88. Hull, E. M., Muschamp, J. W. & Sato, S. Dopamine and serotonin: influences on male sexual behavior. Physiol. Behav. 83, 291–307 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Toghyani, S., Dashti, G. R., Roudbari, N. H., Rouzbehani, S. & Monajemi, R. Lithium carbonate inducing disorders in three parameters of rat sperm. Adv. Biomed. Res. 2, 55 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Thakur, S. C., Thakur, S. S., Chaube, S. K. & Singh, S. P. Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat. Reprod. Toxicol. 17, 683–690 (2003).

    Article  CAS  PubMed  Google Scholar 

  91. Zarnescu, O. & Zamfirescu, G. Effects of lithium carbonate on rat seminiferous tubules: an ultrastructural study. Int. J. Androl. 29, 576–582 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Ko, D. T. et al. β Blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 288, 351–357 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Pérez-Stable, E. J. et al. Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension. J. Gen. Intern. Med. 10, 419–428 (1995).

    Article  PubMed  Google Scholar 

  94. Nusier, M. K., Bataineh, H. N. & Daradka, H. M. Adverse effects of propranolol on reproductive function in adult male mice. Pak. J. Biol. Sci. 10, 2728–2731 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. el-Sayed, M. G. et al. Effects of some β adrenergic blockers on male fertility parameters in rats. Dtsch Tierarztl. Wochenschr. 105, 10–12 (1998).

    CAS  PubMed  Google Scholar 

  96. De Turner, E., Aparicio, N. J., Turner, D. & Schwarzstein, L. Effect of two phosphodiesterase inhibitors, cyclic adenosine 3′:5′ monophosphate, and a β blocking agent on human sperm motility. Fertil. Steril. 29, 328–331 (1978).

    Article  CAS  PubMed  Google Scholar 

  97. White, D. R., Clarkson, J. S., Ratnasooriya, W. D. & Aitken, R. J. Complementary effects of propranolol and nonoxynol 9 upon human sperm motility. Contraception 52, 241–247 (1995).

    Article  CAS  PubMed  Google Scholar 

  98. Corvol, P., Michaud, A., Menard, J., Freifeld, M. & Mahoudeau, J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology 97, 52–58 (1975).

    Article  CAS  PubMed  Google Scholar 

  99. Wong, P. Y. & Lee, W. M. Effects of spironolactone (aldosterone antagonist) on electrolyte and water content of the cauda epididymidis and fertility of male rats. Biol. Reprod. 27, 771–777 (1982).

    Article  CAS  PubMed  Google Scholar 

  100. Clark, E. Spironolactone therapy and gynecomastia. JAMA 193, 163–164 (1965).

    Article  CAS  PubMed  Google Scholar 

  101. Caminos-Torres, R., Ma, L. & Snyder, P. J. Gynecomastia and semen abnormalities induced by spironolactone in normal men. J. Clin. Endocrinol. Metab. 45, 255–260 (1977).

    Article  CAS  PubMed  Google Scholar 

  102. Li, L. J. et al. Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization. Biol. Reprod. 90, 125 (2014).

    PubMed  Google Scholar 

  103. Hagaman, J. R. et al. Angiotensin-converting enzyme and male fertility. Proc. Natl Acad. Sci. USA 95, 2552–2557 (1998).

    Article  CAS  PubMed  Google Scholar 

  104. Zalata, A. A., Morsy, H. K., Badawy, A. E., Elhanbly, S. & Mostafa, T. ACE gene insertion/deletion polymorphism seminal associations in infertile men. J. Urol. 187, 1776–1780 (2012).

    Article  CAS  PubMed  Google Scholar 

  105. Kondoh, G. et al. Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat. Med. 11, 160–166 (2005).

    Article  CAS  PubMed  Google Scholar 

  106. Okeahialam, B. N., Amadi, K. & Ameh, A. S. Effect of lisnopril, an angiotensin converting enzyme (ACE) inhibitor on spermatogenesis in rats. Arch. Androl. 52, 209–213 (2006).

    Article  CAS  PubMed  Google Scholar 

  107. Saha, L., Garg, S. K., Bhargava, V. K. & Mazumdar, S. Role of angiotensin-converting enzyme inhibitor, lisinopril, on spermatozoal functions in rats. Methods Find. Exp. Clin. Pharmacol. 22, 159–162 (2000).

    CAS  PubMed  Google Scholar 

  108. Yao, H. X. & Liu, J. H. Influence of captopril on human sperm motility parameters in vitro [Chinese]. Zhonghua Nan Ke Xue 12, 435–437 (2006).

    PubMed  Google Scholar 

  109. Morakinyo, A. O., Iranloye, B. O., Daramola, A. O. & Adegoke, O. A. Antifertility effect of calcium channel blockers on male rats: association with oxidative stress. Adv. Med. Sci. 56, 95–105 (2011).

    Article  CAS  PubMed  Google Scholar 

  110. Hershlag, A. et al. Mannose ligand receptor assay as a test to predict fertilization in vitro: a prospective study. Fertil. Steril. 70, 482–491 (1998).

    Article  CAS  PubMed  Google Scholar 

  111. Saha, L., Bhargava, V. K., Garg, S. K. & Majumdar, S. Effect of nimodipine on male reproductive functions in rats. Indian J. Physiol. Pharmacol. 44, 449–455 (2000).

    CAS  PubMed  Google Scholar 

  112. Lee, J. H., Ahn, H. J., Lee, S. J., Gye, M. C. & Min, C. K. Effects of L and T type Ca²+ channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis. J. Assist. Reprod. Genet. 28, 23–30 (2011).

    Article  PubMed  Google Scholar 

  113. Feng, H. L., Han, Y. B., Hershlag, A. & Zheng, L. J. Impact of Ca2+ flux inhibitors on acrosome reaction of hamster spermatozoa. J. Androl. 28, 561–564 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Li, L., Liu, J., Li, J. & Ye, Z. Pharmacological investigation of voltage-dependent Ca2+ channels in human ejaculatory sperm in vitro. J. Huazhong Univ. Sci. Technolog. Med. Sci. 26, 607–609 (2006).

    Article  CAS  PubMed  Google Scholar 

  115. Katsoff, D. & Check, J. H. A challenge to the concept that the use of calcium channel blockers causes reversible male infertility. Hum. Reprod. 12, 1480–1482 (1997).

    Article  CAS  PubMed  Google Scholar 

  116. Hargreaves, C. A. et al. Effects of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine on sperm function in vitro. Hum. Reprod. 13, 1878–1886 (1998).

    Article  CAS  PubMed  Google Scholar 

  117. Andrews, J. C. & Bavister, B. D. Capacitation of hamster spermatozoa with the divalent cation chelators D penicillamine, L histidine, and L cysteine in a protein-free culture medium. Gamete Res. 23, 159–170 (1989).

    Article  CAS  PubMed  Google Scholar 

  118. Timmermans, L. Influence of antibiotics on spermatogenesis. J. Urol. 112, 348–349 (1974).

    Article  CAS  PubMed  Google Scholar 

  119. Murdia, A., Mathur, V., Kothari, L. K. & Singh, K. P. Sulpha-trimethoprim combinations and male fertility. Lancet 2, 375–376 (1978).

    Article  CAS  PubMed  Google Scholar 

  120. Merino, G. & Carranza-Lira, S. Infection and male infertility: effect of different antibiotic regimens on semen quality. Arch. Androl. 35, 209–212 (1995).

    Article  CAS  PubMed  Google Scholar 

  121. Albert, P. S., Mininberg, D. T. & Davis, J. E. The nitrofurans as sperm immobilising agents: their tissue toxicity and their clinical application. Br. J. Urol. 47, 459–462 (1975).

    Article  CAS  PubMed  Google Scholar 

  122. Schlegel, P. N., Chang, T. S. & Marshall, F. F. Antibiotics: potential hazards to male fertility. Fertil. Steril. 55, 235–242 (1991).

    Article  CAS  PubMed  Google Scholar 

  123. Albert, P. S., Salerno, R. G., Kapoor, S. N. & Davis, J. E. The nitrofurans as sperm-immobilizing agents, their tissue toxicity, and their clinical application in vasectomy. Fertil. Steril. 26, 485–491 (1975).

    Article  CAS  PubMed  Google Scholar 

  124. Nelson, W. O. & Bunge, R. G. The effect of therapeutic dosages of nitrofurantoin (furadantin) upon spermatogenesis in man. J. Urol. 77, 275–281 (1957).

    Article  CAS  PubMed  Google Scholar 

  125. Baker, H. W. et al. A controlled trial of the use of erythromycin for men with asthenospermia. Int. J. Androl. 7, 383–388 (1984).

    Article  CAS  PubMed  Google Scholar 

  126. White, I. G. The toxicity of some antibacterials for bull, ram, rabbit and human spermatozoa. Aust. J. Exp. Biol. Med. Sci. 32, 41–48 (1954).

    Article  CAS  PubMed  Google Scholar 

  127. Fukushima, T. et al. Early changes in sperm motility, acrosome reaction, and gene expression of reproductive organs in rats treated with sulfasalazine. Reprod. Toxicol. 23, 153–157 (2007).

    Article  CAS  PubMed  Google Scholar 

  128. Sutyak, K. E. et al. Spermicidal activity of the safe natural antimicrobial peptide subtilosin. Infect. Dis. Obstet. Gynecol. 2008, 540758 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Pont, A. et al. Ketoconazole blocks testosterone synthesis. Arch. Intern. Med. 142, 2137–2140 (1982).

    Article  CAS  PubMed  Google Scholar 

  130. Heckman, W. R., Kane, B. R., Pakyz, R. E. & Cosentino, M. J. The effect of ketoconazole on endocrine and reproductive parameters in male mice and rats. J. Androl. 13, 191–198 (1992).

    CAS  PubMed  Google Scholar 

  131. Joshi, S. C., Jain, G. C. & Lata, M. Effects of ketoconazole (an imidazole antifugal agent) on the fertility and reproductive function of male mice. Acta Eur. Fertil. 25, 55–58 (1994).

    CAS  PubMed  Google Scholar 

  132. Meistrich, M. L. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil. Steril. 100, 1180–1186 (2013).

    Article  CAS  PubMed  Google Scholar 

  133. Boekelheide, K. Mechanisms of toxic damage to spermatogenesis. J. Natl Cancer Inst. Monogr. 2005, 6–8 (2005).

    Article  CAS  Google Scholar 

  134. Genescà, A. et al. Sperm chromosome studies in individuals treated for testicular cancer. Hum. Reprod. 5, 286–290 (1990).

    Article  PubMed  Google Scholar 

  135. De Mas, P. et al. Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin. Hum. Reprod. 16, 1204–1208 (2001).

    Article  CAS  PubMed  Google Scholar 

  136. Genescà, A. et al. Human sperm chromosomes. Long-term effect of cancer treatment. Cancer Genet. Cytogenet. 46, 251–260 (1990).

    Article  PubMed  Google Scholar 

  137. Nangia, A. K., Krieg, S. A. & Kim, S. S. Clinical guidelines for sperm cryopreservation in cancer patients. Fertil. Steril. 100, 1203–1209 (2013).

    Article  PubMed  Google Scholar 

  138. Pont, J. & Albrecht, W. Fertility after chemotherapy for testicular germ cell cancer. Fertil. Steril. 68, 1–5 (1997).

    Article  CAS  PubMed  Google Scholar 

  139. Howell, S. J. & Shalet, S. M. Testicular function following chemotherapy. Hum. Reprod. Update 7, 363–369 (2001).

    Article  CAS  PubMed  Google Scholar 

  140. Wallace, W. H., Anderson, R. A. & Irvine, D. S. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol. 6, 209–218 (2005).

    Article  PubMed  Google Scholar 

  141. Fung, C. & Vaughn, D. J. Complications associated with chemotherapy in testicular cancer management. Nat. Rev. Urol. 8, 213–222 (2011).

    Article  CAS  PubMed  Google Scholar 

  142. Brydøy, M. et al. Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer. Br. J. Cancer 107, 1833–1839 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Huddart, R. A. et al. Fertility, gonadal and sexual function in survivors of testicular cancer. Br. J. Cancer 93, 200–207 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Wiechno, P., Demkow, T., Kubiak, K., Sadowska, M. & Kamin´ska, J. The quality of life and hormonal disturbances in testicular cancer survivors in cisplatin era. Eur. Urol. 52, 1448–1454 (2007).

    Article  PubMed  Google Scholar 

  145. da Cunha, M. F. et al. Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy. J. Clin. Oncol. 2, 571–577 (1984).

    Article  CAS  PubMed  Google Scholar 

  146. Bujan, L. et al. Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network. Fertil. Steril. 102, 667–674.e3 (2014).

    Article  CAS  PubMed  Google Scholar 

  147. Eghbali, H. & Papaxanthos-Roche, A. The impact of lymphoma and treatment on male fertility. Expert Rev. Hematol. 3, 775–788 (2010).

    Article  PubMed  Google Scholar 

  148. Meistrich, M. L. et al. Recovery of sperm production after chemotherapy for osteosarcoma. Cancer 63, 2115–2123 (1989).

    Article  CAS  PubMed  Google Scholar 

  149. Rivkees, S. A. & Crawford, J. D. The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA 259, 2123–2125 (1988).

    Article  CAS  PubMed  Google Scholar 

  150. Meistrich, M. L., Wilson, G., Brown, B. W., da Cunha, M. F. & Lipshultz, L. I. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer 70, 2703–2712 (1992).

    Article  CAS  PubMed  Google Scholar 

  151. Johnson, D. H. et al. Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations. Blood 65, 832–836 (1985).

    CAS  PubMed  Google Scholar 

  152. Meistrich, M. L. & Shetty, G. Hormonal suppression for fertility preservation in males and females. Reproduction 136, 691–701 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Tournaye, H. et al. Preserving the reproductive potential of men and boys with cancer: current concepts and future prospects. Hum. Reprod. Update 10, 525–532 (2004).

    Article  PubMed  Google Scholar 

  154. Clark, A. T., Phillips, B. T. & Orwig, K. E. Fruitful progress to fertility: male fertility in the test tube. Nat. Med. 17, 1564–1565 (2011).

    Article  CAS  PubMed  Google Scholar 

  155. Brinster, R. L. & Avarbock, M. R. Germline transmission of donor haplotype following spermatogonial transplantation. Proc. Natl Acad. Sci. USA 91, 11303–11307 (1994).

    Article  CAS  PubMed  Google Scholar 

  156. Brinster, R. L. & Zimmermann, J. W. Spermatogenesis following male germ-cell transplantation. Proc. Natl Acad. Sci. USA 91, 11298–11302 (1994).

    Article  CAS  PubMed  Google Scholar 

  157. Nurmio, M., Kallio, J., Toppari, J. & Jahnukainen, K. Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c kit and PDGFR, in the rat testis. Reprod. Toxicol. 25, 442–446 (2008).

    Article  CAS  PubMed  Google Scholar 

  158. Schultheis, B., Nijmeijer, B. A., Yin, H., Gosden, R. G. & Melo, J. V. Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model. Leuk. Res. 36, 271–274 (2012).

    Article  CAS  PubMed  Google Scholar 

  159. Apperley, J. CML in pregnancy and childhood. Best Pract. Res. Clin. Haematol. 22, 455–474 (2009).

    Article  CAS  PubMed  Google Scholar 

  160. Ault, P. et al. Pregnancy among patients with chronic myeloid leukemia treated with imatinib. J. Clin. Oncol. 24, 1204–1208 (2006).

    Article  CAS  PubMed  Google Scholar 

  161. Shash, E. et al. Fatherhood during imatinib. Acta Oncol. 50, 734–735 (2011).

    Article  PubMed  Google Scholar 

  162. Gambacorti-Passerini, C. et al. Gynaecomastia in men with chronic myeloid leukaemia after imatinib. Lancet 361, 1954–1956 (2003).

    Article  PubMed  Google Scholar 

  163. Caocci, G. et al. Gynecomastia in a male after dasatinib treatment for chronic myeloid leukemia. Leukemia 22, 2127–2128 (2008).

    Article  CAS  PubMed  Google Scholar 

  164. Ballardini, P., Margutti, G., Aliberti, C. & Manfredini, R. Onset of male gynaecomastia in a patient treated with sunitinib for metastatic renal cell carcinoma. Clin. Drug Investig. 29, 487–490 (2009).

    Article  CAS  PubMed  Google Scholar 

  165. Coburn, A. M., Cappon, G. D., Bowman, C. J., Stedman, D. B. & Patyna, S. Reproductive toxicity assessment of sunitinib, a multitargeted receptor tyrosine kinase inhibitor, in male and female rats. Birth Defects Res. B Dev. Reprod. Toxicol. 95, 267–275 (2012).

    Article  CAS  PubMed  Google Scholar 

  166. Oweini, H., Otrock, Z. K., Mahfouz, R. A. & Bazarbachi, A. Successful pregnancy involving a man with chronic myeloid leukemia on dasatinib. Arch. Gynecol. Obstet. 283, 133–134 (2011).

    Article  PubMed  Google Scholar 

  167. Cortes, J. et al. Pregnancy outcomes among patients with chronic myeloid leukemia treated with dasatinib [abstract 3230]. Blood 112, ASH Annual Meeting Abstracts (2008).

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Authors and Affiliations

  1. Institute of Urology, University of Southern California, 1441 Eastlake Avenue, NOR 7416, Los Angeles, 90033-9178, CA, USA

    Mary K. Samplaski

  2. Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, 66160, KS, USA

    Ajay K. Nangia

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Both authors researched data for the article, made substantial contributions to discussions of content, wrote the article and reviewed and edited the manuscript before submission.

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Samplaski, M., Nangia, A. Adverse effects of common medications on male fertility. Nat Rev Urol 12, 401–413 (2015). https://doi.org/10.1038/nrurol.2015.145

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