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
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.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
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).
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).
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).
Alonso, V. et al. Sulfasalazine induced oxidative stress: a possible mechanism of male infertility. Reprod. Toxicol. 27, 35–40 (2009).
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).
Handelsman, D. J. Pharmacoepidemiology of testosterone prescribing in Australia, 1992–2010. Med. J. Aust. 196, 642–645 (2012).
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).
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).
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).
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).
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).
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).
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).
Gu, Y. et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J. Clin. Endocrinol. Metab. 94, 1910–1915 (2009).
Liu, P. Y. et al. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 367, 1412–1420 (2006).
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).
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).
Eaton, D. K. et al. Youth risk behavior surveillance—United States, 2011. MMWR Surveill. Summ. 61, 1–162 (2012).
Ito, T. & Horton, R. The source of plasma dihydrotestosterone in man. J. Clin. Invest. 50, 1621–1627 (1971).
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).
Nepple, K. G. & Andriole, G. L. Prostate cancer chemoprevention with 5α-reductase inhibitors. Urol. Oncol. 30, 553–554 (2012).
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).
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).
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).
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).
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).
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).
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).
Tu, H. Y. & Zini, A. Finasteride-induced secondary infertility associated with sperm DNA damage. Fertil. Steril. 95, 2125.e13–2125.e14 (2011).
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).
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).
Irwig, M. S. & Kolukula, S. Persistent sexual side effects of finasteride for male pattern hair loss. J. Sex. Med. 8, 1747–1753 (2011).
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).
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).
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).
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).
McClellan, K. J. & Markham, A. Finasteride: a review of its use in male pattern hair loss. Drugs 57, 111–126 (1999).
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).
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).
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).
Lowe, F. C. et al. Long-term 6 year experience with finasteride in patients with benign prostatic hyperplasia. Urology 61, 791–796 (2003).
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).
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).
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).
Furukawa, K. et al. α 1A adrenoceptor mediated contractile responses of the human vas deferens. Br. J. Pharmacol. 116, 1605–1610 (1995).
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).
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).
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).
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).
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).
Kaplan, S. A. Side effects of α blocker use: retrograde ejaculation. Rev. Urol. 11 (Suppl. 1), S14–S18 (2009).
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).
Lepor, H., Kazzazi, A. & Djavan, B. α Blockers for benign prostatic hyperplasia: the new era. Curr. Opin. Urol. 22, 7–15 (2012).
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).
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).
Sinclair, M. L. et al. Specific expression of soluble adenylyl cyclase in male germ cells. Mol. Reprod. Dev. 56, 6–11 (2000).
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).
Su, Y. H. & Vacquier, V. D. Cyclic GMP-specific phosphodiesterase 5 regulates motility of sea urchin spermatozoa. Mol. Biol. Cell 17, 114–121 (2006).
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).
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).
Makhlouf, A., Kshirsagar, A. & Niederberger, C. Phosphodiesterase 11: a brief review of structure, expression and function. Int. J. Impot. Res. 18, 501–509 (2006).
Wayman, C. et al. Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology. Int. J. Impot. Res. 17, 216–223 (2005).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Lilly USA, LLC. Highlights of prescribing information. CIALIS (tadalafil) tablets, for oral use [online], (2014).
Hellstrom, W. J. et al. Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones. J. Urol. 170, 887–891 (2003).
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).
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).
Carter, M. D., Hollander, M. B. & Lipshultz, L. I. In the medicine cabinet, clues to infertility. Contemp. Urol. 5, 51–63 (1993).
Hendrick, V., Gitlin, M., Altshuler, L. & Korenman, S. Antidepressant medications, mood and male fertility. Psychoneuroendocrinology 25, 37–51 (2000).
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).
Kumar, V. S. et al. The spermicidal and antitrichomonas activities of SSRI antidepressants. Bioorg. Med. Chem. Lett. 16, 2509–2512 (2006).
Tanrikut, C. & Schlegel, P. N. Antidepressant-associated changes in semen parameters. Urology 69, 185.e5–185.e7 (2007).
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).
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).
Maier, U. & Koinig, G. Andrological findings in young patients under long-term antidepressive therapy with clomipramine. Psychopharmacology (Berl.) 116, 357–359 (1994).
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).
Wilson, B. The effect of drugs on male sexual function and fertility. Nurse Pract. 16, 12–17, 21–24 (1991).
Serretti, A. & Chiesa, A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin. Pharmacol. Ther. 89, 142–147 (2011).
Hull, E. M., Muschamp, J. W. & Sato, S. Dopamine and serotonin: influences on male sexual behavior. Physiol. Behav. 83, 291–307 (2004).
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).
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).
Zarnescu, O. & Zamfirescu, G. Effects of lithium carbonate on rat seminiferous tubules: an ultrastructural study. Int. J. Androl. 29, 576–582 (2006).
Ko, D. T. et al. β Blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 288, 351–357 (2002).
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).
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).
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).
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).
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).
Corvol, P., Michaud, A., Menard, J., Freifeld, M. & Mahoudeau, J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology 97, 52–58 (1975).
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).
Clark, E. Spironolactone therapy and gynecomastia. JAMA 193, 163–164 (1965).
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).
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).
Hagaman, J. R. et al. Angiotensin-converting enzyme and male fertility. Proc. Natl Acad. Sci. USA 95, 2552–2557 (1998).
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).
Kondoh, G. et al. Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat. Med. 11, 160–166 (2005).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Timmermans, L. Influence of antibiotics on spermatogenesis. J. Urol. 112, 348–349 (1974).
Murdia, A., Mathur, V., Kothari, L. K. & Singh, K. P. Sulpha-trimethoprim combinations and male fertility. Lancet 2, 375–376 (1978).
Merino, G. & Carranza-Lira, S. Infection and male infertility: effect of different antibiotic regimens on semen quality. Arch. Androl. 35, 209–212 (1995).
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).
Schlegel, P. N., Chang, T. S. & Marshall, F. F. Antibiotics: potential hazards to male fertility. Fertil. Steril. 55, 235–242 (1991).
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).
Nelson, W. O. & Bunge, R. G. The effect of therapeutic dosages of nitrofurantoin (furadantin) upon spermatogenesis in man. J. Urol. 77, 275–281 (1957).
Baker, H. W. et al. A controlled trial of the use of erythromycin for men with asthenospermia. Int. J. Androl. 7, 383–388 (1984).
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).
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).
Sutyak, K. E. et al. Spermicidal activity of the safe natural antimicrobial peptide subtilosin. Infect. Dis. Obstet. Gynecol. 2008, 540758 (2008).
Pont, A. et al. Ketoconazole blocks testosterone synthesis. Arch. Intern. Med. 142, 2137–2140 (1982).
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).
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).
Meistrich, M. L. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil. Steril. 100, 1180–1186 (2013).
Boekelheide, K. Mechanisms of toxic damage to spermatogenesis. J. Natl Cancer Inst. Monogr. 2005, 6–8 (2005).
Genescà, A. et al. Sperm chromosome studies in individuals treated for testicular cancer. Hum. Reprod. 5, 286–290 (1990).
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).
Genescà, A. et al. Human sperm chromosomes. Long-term effect of cancer treatment. Cancer Genet. Cytogenet. 46, 251–260 (1990).
Nangia, A. K., Krieg, S. A. & Kim, S. S. Clinical guidelines for sperm cryopreservation in cancer patients. Fertil. Steril. 100, 1203–1209 (2013).
Pont, J. & Albrecht, W. Fertility after chemotherapy for testicular germ cell cancer. Fertil. Steril. 68, 1–5 (1997).
Howell, S. J. & Shalet, S. M. Testicular function following chemotherapy. Hum. Reprod. Update 7, 363–369 (2001).
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).
Fung, C. & Vaughn, D. J. Complications associated with chemotherapy in testicular cancer management. Nat. Rev. Urol. 8, 213–222 (2011).
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).
Huddart, R. A. et al. Fertility, gonadal and sexual function in survivors of testicular cancer. Br. J. Cancer 93, 200–207 (2005).
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).
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).
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).
Eghbali, H. & Papaxanthos-Roche, A. The impact of lymphoma and treatment on male fertility. Expert Rev. Hematol. 3, 775–788 (2010).
Meistrich, M. L. et al. Recovery of sperm production after chemotherapy for osteosarcoma. Cancer 63, 2115–2123 (1989).
Rivkees, S. A. & Crawford, J. D. The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA 259, 2123–2125 (1988).
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).
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).
Meistrich, M. L. & Shetty, G. Hormonal suppression for fertility preservation in males and females. Reproduction 136, 691–701 (2008).
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).
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).
Brinster, R. L. & Avarbock, M. R. Germline transmission of donor haplotype following spermatogonial transplantation. Proc. Natl Acad. Sci. USA 91, 11303–11307 (1994).
Brinster, R. L. & Zimmermann, J. W. Spermatogenesis following male germ-cell transplantation. Proc. Natl Acad. Sci. USA 91, 11298–11302 (1994).
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).
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).
Apperley, J. CML in pregnancy and childhood. Best Pract. Res. Clin. Haematol. 22, 455–474 (2009).
Ault, P. et al. Pregnancy among patients with chronic myeloid leukemia treated with imatinib. J. Clin. Oncol. 24, 1204–1208 (2006).
Shash, E. et al. Fatherhood during imatinib. Acta Oncol. 50, 734–735 (2011).
Gambacorti-Passerini, C. et al. Gynaecomastia in men with chronic myeloid leukaemia after imatinib. Lancet 361, 1954–1956 (2003).
Caocci, G. et al. Gynecomastia in a male after dasatinib treatment for chronic myeloid leukemia. Leukemia 22, 2127–2128 (2008).
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).
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).
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).
Cortes, J. et al. Pregnancy outcomes among patients with chronic myeloid leukemia treated with dasatinib [abstract 3230]. Blood 112, ASH Annual Meeting Abstracts (2008).
The authors declare no competing financial interests.
About this article
Cite this article
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
Scientific Reports (2022)
Reversible infertility in male dog following prolonged treatment of Malassezia dermatitis with ketoconazole
Acta Veterinaria Scandinavica (2021)
Nature Reviews Urology (2018)