Skip to main content

Advertisement

SpringerLink
Log in

Male hormonal contraception: Potential risks and benefits

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

An effective, safe, reversible, and acceptable method of contraception is an important component of reproductive health and provides the opportunity of shared responsibility for family planning for both partners. Female hormonal contraceptives have been proven to be safe, reversible, available and widely acceptable by different populations. In contrast, male hormonal contraception, despite significant progress showing contraceptive efficacy comparable to female hormonal methods during last three decades, has not yet led to an approved product. Safety of a pharmaceutical product is an appropriate concern but the majority of male hormonal contraceptive clinical trials have not reported significant short term safety concerns. While the absence of serious adverse effects is encouraging, the studies have been designed for efficacy endpoints not long term safety. In this review we summarize potential risks and benefits of putative male hormonal contraceptives on reproductive and non-reproductive organs. While the review covers what we believe will be the likely class of drugs used for male hormonal contraception a true assessment of long term risks and benefits cannot be achieved without an available product.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Trussell J. Understanding contraceptive failure. Best Pract Res Clin Obstet Gynaecol. 2009;23(2):199–209.

    Article  PubMed  Google Scholar 

  2. Shridharani A, Sandlow JI. Vasectomy reversal versus IVF with sperm retrieval: which is better? Curr Opin Urol. 2010;20(6):503–9.

    Article  PubMed  Google Scholar 

  3. Wang C, Swerdloff RS. Hormonal approaches to male contraception. Curr Opin Urol. 2010;20(6):520–4.

    Article  PubMed  CAS  Google Scholar 

  4. Page ST, Amory JK, Bremner WJ. Advances in male contraception. Endocr Rev. 2008;29(4):465–93.

    Article  PubMed  CAS  Google Scholar 

  5. Nieschlag E. Clinical trials in male hormonal contraception. Contraception. 2010;82(5):457–70.

    Article  PubMed  CAS  Google Scholar 

  6. World Health Organization Task Force on methods for the regulation of male fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril. 1996;65(4):821–9.

    Google Scholar 

  7. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet. 1990;336(8721):955–9.

    Article  Google Scholar 

  8. Turner L, Conway AJ, Jimenez M, Liu PY, Forbes E, McLachlan RI, et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab. 2003;88(10):4659–67.

    Article  PubMed  CAS  Google Scholar 

  9. Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab. 2009;94(6):1910–5.

    Article  PubMed  CAS  Google Scholar 

  10. Nieschlag E. Male hormonal contraception: love’s labour’s lost? J Clin Endocrinol Metab. 2009;94(6):1890–2.

    Article  PubMed  CAS  Google Scholar 

  11. Aaltonen P, Amory JK, Anderson RA, Behre HM, Bialy G, Blithe D, et al. 10th Summit Meeting consensus: recommendations for regulatory approval for hormonal male contraception. J Androl. 2007;28(3):362–3.

    Article  PubMed  Google Scholar 

  12. Handelsman DJ, Farley TM, Peregoudov A, Waites GM. Factors in nonuniform induction of azoospermia by testosterone enanthate in normal men. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1995;63(1):125–33.

    PubMed  CAS  Google Scholar 

  13. Liu PY, Swerdloff RS, Anawalt BD, Anderson RA, Bremner WJ, Elliesen J, et al. Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: An integrated analysis. J Clin Endocrinol Metab. 2008;93(5):1774–83.

    Article  PubMed  CAS  Google Scholar 

  14. 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(9520):1412–20.

    Article  PubMed  CAS  Google Scholar 

  15. Liverman CT, Blazer DG. Testosterone and aging: clinical research directions. Washington, DC: National Academies; 2004.

    Google Scholar 

  16. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996;81(12):4358–65.

    Article  PubMed  CAS  Google Scholar 

  17. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004;89(5):2085–98.

    Article  PubMed  CAS  Google Scholar 

  18. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2670–7.

    Article  PubMed  CAS  Google Scholar 

  19. Wang C, Swedloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group. J Clin Endocrinol Metab. 2000;85(8):2839–53.

    Article  PubMed  CAS  Google Scholar 

  20. Herbst KL, Bhasin S. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. 2004;7(3):271–7.

    Article  PubMed  CAS  Google Scholar 

  21. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996;335(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  22. Young NR, Baker HW, Liu G, Seeman E. Body composition and muscle strength in healthy men receiving testosterone enanthate for contraception. J Clin Endocrinol Metab. 1993;77(4):1028–32.

    Article  PubMed  CAS  Google Scholar 

  23. Herbst KL, Anawalt BD, Amory JK, Matsumoto AM, Bremner WJ. The male contraceptive regimen of testosterone and levonorgestrel significantly increases lean mass in healthy young men in 4 weeks, but attenuates a decrease in fat mass induced by testosterone alone. J Clin Endocrinol Metab. 2003;88(3):1167–73.

    Article  PubMed  CAS  Google Scholar 

  24. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. AJP - Endocrinol Metabolism. 2003;285(1):E197–205.

    CAS  Google Scholar 

  25. Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab. 2004;89(10):5245–55.

    Article  PubMed  CAS  Google Scholar 

  26. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens Stimulate Myogenic Differentiation and Inhibit Adipogenesis in C3H 10T1/2 Pluripotent Cells through an Androgen Receptor-Mediated Pathway. Endocrinology. 2003;144(11):5081–8.

    Article  PubMed  CAS  Google Scholar 

  27. Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997;82(8):2386–90.

    Article  PubMed  CAS  Google Scholar 

  28. Khosla S, Bilezikian JP. The role of estrogens in men and androgens in women. Endocrinol Metab Clin North Am. 2003;32(1):195–218.

    Article  PubMed  CAS  Google Scholar 

  29. Mommers E, Kersemaekers WM, Elliesen J, Kepers M, Apter D, Behre HM, et al. Male hormonal contraception: a double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2008;93(7):2572–80.

    Article  PubMed  CAS  Google Scholar 

  30. Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1996;65(3):626–36.

    PubMed  CAS  Google Scholar 

  31. Bebb RA, Anawalt BD, Christensen RB, Paulsen CA, Bremner WJ, Matsumoto AM. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach. J Clin Endocrinol Metab. 1996;81(2):757–62.

    Article  PubMed  CAS  Google Scholar 

  32. Hay CJ, Brady BM, Zitzmann M, Osmanagaoglu K, Pollanen P, Apter D, et al. A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception. J Clin Endocrinol Metab. 2005;90(4):2042–9.

    Article  PubMed  CAS  Google Scholar 

  33. Mahabadi V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, et al. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men. J Clin Endocrinol Metab. 2009;94(7):2313–20.

    Article  PubMed  CAS  Google Scholar 

  34. Gonzalo ITG, Swerdloff RS, Nelson AL, Clevenger B, Garcia R, Berman N, et al. Levonorgestrel implants (Norplant II) for male contraception clinical trials: combination with transdermal and injectable testosterone. J Clin Endocrinol Metab. 2002;87(8):3562–72.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ. A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men. J Clin Endocrinol Metab. 1999;84(10):3642–7.

    Article  PubMed  CAS  Google Scholar 

  36. McLachlan RI, O’Donnell L, Meachem SJ, Stanton PG, de K, Pratis K, et al. Hormonal regulation of spermatogenesis in primates and man: insights for development of the male hormonal contraceptive. J Androl. 2002;23(2):149–62.

    PubMed  CAS  Google Scholar 

  37. Wang C, Cui YG, Wang XH, Jia Y, Sinha HA, Lue YH, et al. Transient scrotal hyperthermia and levonorgestrel enhance testosterone-induced spermatogenesis suppression in men through increased germ cell apoptosis. J Clin Endocrinol Metab. 2007;92(8):3292–304.

    Article  PubMed  CAS  Google Scholar 

  38. Wang C, Wang XH, Nelson AL, Lee KK, Cui YG, Tong JS, et al. Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men. J Clin Endocrinol Metab. 2006;91(2):460–70.

    Article  PubMed  CAS  Google Scholar 

  39. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412–20.

    Article  PubMed  CAS  Google Scholar 

  40. Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914–9.

    Article  PubMed  CAS  Google Scholar 

  41. Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95(6):2560–75.

    Article  PubMed  CAS  Google Scholar 

  42. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59.

    Article  PubMed  CAS  Google Scholar 

  43. Bachman E, Feng R, Travison T, Li M, Olbina G, Ostland V, et al. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J Clin Endocrinol Metab. 2010;95(10):4743–7.

    Article  PubMed  CAS  Google Scholar 

  44. Gu YQ, Tong JS, Ma DZ, Wang XH, Yuan D, Tang WH, et al. Male hormonal contraception: effects of injections of testosterone undecanoate and depot medroxyprogesterone acetate at eight-week intervals in chinese men. J Clin Endocrinol Metab. 2004;89(5):2254–62.

    Article  PubMed  CAS  Google Scholar 

  45. Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, et al. A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab. 2003;88(2):562–8.

    Article  PubMed  CAS  Google Scholar 

  46. Wang C, Wang XH, Nelson AL, Lee KK, Cui YG, Tong JS, et al. Levonorgestrel implants enhanced the suppression of spermatogenesis by testosterone implants: comparison between Chinese and non-Chinese men. J Clin Endocrinol Metab. 2006;91(2):460–70.

    Article  PubMed  CAS  Google Scholar 

  47. Gui YL, He CH, Amory JK, Bremner WJ, Zheng EX, Yang J, et al. Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men. J Androl. 2004;25(5):720–7.

    PubMed  CAS  Google Scholar 

  48. Kinniburgh D, Zhu H, Cheng L, Kicman AT, Baird DT, Anderson RA. Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men. Hum Reprod. 2002;17(6):1490–501.

    Article  PubMed  CAS  Google Scholar 

  49. Meriggiola MC, Bremner WJ, Costantino A, Pavani A, Capelli M, Flamigni C. An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men. Fertil Steril. 1997;68(5):844–50.

    Article  PubMed  CAS  Google Scholar 

  50. Meriggiola MC, Bremner WJ, Paulsen CA, Valdiserri A, Incorvaia L, Motta R, et al. A combined regimen of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab. 1996;81(8):3018–23.

    Article  PubMed  CAS  Google Scholar 

  51. Zitzmann M, Junker R, Kamischke A, Nieschlag E. Contraceptive steroids influence the hemostatic activation state in healthy men. J Androl. 2002;23(4):503–11.

    PubMed  CAS  Google Scholar 

  52. Agledahl I, Brodin E, Svartberg J, Hansen JB. Impact of long-term testosterone treatment on plasma levels of free TFPI and TF-induced thrombin generation ex vivo in elderly men with low testosterone levels. Thromb Haemost. 2009;102(5):945–50.

    PubMed  CAS  Google Scholar 

  53. Brodin E, Vikan T, Hansen JB, Svartberg J. Testosterone, hemostasis, and cardiovascular diseases in men. Semin Thromb Hemost. 2011;37(1):87–94.

    Article  PubMed  CAS  Google Scholar 

  54. Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. Am J Obstet Gynecol. 2004;190(4 Suppl):S5–S22.

    Article  PubMed  CAS  Google Scholar 

  55. Gerstman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Lundin FE. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am J Epidemiol. 1991;133(1):32–7.

    PubMed  CAS  Google Scholar 

  56. Sulak P, Willis S, Kuehl T, Coffee A, Clark J. Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache. 2007;47(1):27–37.

    Article  PubMed  Google Scholar 

  57. Pakalnis A, Gladstein J. Headaches and hormones. Semin Pediatr Neurol. 2010;17(2):100–4.

    Article  PubMed  Google Scholar 

  58. Pangkahila W. Reversible azoospermia induced by an androgen-progestin combination regimen in Indonesian men. Int J Androl. 1991;14(4):248–56.

    Article  PubMed  CAS  Google Scholar 

  59. Anawalt BD, Herbst KL, Matsumoto AM, Mulders TM, Coelingh-Bennink HJ, Bremner WJ. Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression. Fertil Steril. 2000;74(4):707–14.

    Article  PubMed  CAS  Google Scholar 

  60. Anawalt BD, Amory JK, Herbst KL, Coviello AD, Page ST, Bremner WJ, et al. Intramuscular testosterone enanthate plus very low dosage oral levonorgestrel suppresses spermatogenesis without causing weight gain in normal young men: a randomized clinical trial. J Androl. 2005;26(3):405–13.

    Article  PubMed  CAS  Google Scholar 

  61. Friedl KE, Hannan Jr CJ, Jones RE, Plymate SR. High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Metabolism. 1990;39(1):69–74.

    Article  PubMed  CAS  Google Scholar 

  62. Herbst KL, Amory JK, Brunzell JD, Chansky HA, Bremner WJ. Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk. Am J Physiol Endocrinol Metab. 2003;284(6):E1112–8.

    PubMed  CAS  Google Scholar 

  63. Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004;351(25):2599–610.

    Article  PubMed  CAS  Google Scholar 

  64. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89(7):3313–8.

    Article  PubMed  CAS  Google Scholar 

  65. Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010;73(5):602–12.

    Article  CAS  Google Scholar 

  66. Zitzmann M, Erren M, Kamischke A, Simoni M, Nieschlag E. Endogenous progesterone and the exogenous progestin norethisterone enanthate are associated with a proinflammatory profile in healthy men. J Clin Endocrinol Metab. 2005;90(12):6603–8.

    Article  PubMed  CAS  Google Scholar 

  67. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003;24(2):183–217.

    Article  PubMed  CAS  Google Scholar 

  68. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev. 2003;24(3):313–40.

    Article  PubMed  CAS  Google Scholar 

  69. Yeap BB. Androgens and cardiovascular disease. Curr Opin Endocrinol Diab Obes. 2010;17(3):269–76.

    Article  CAS  Google Scholar 

  70. Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821–5.

    Article  PubMed  CAS  Google Scholar 

  71. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75.

    Article  PubMed  CAS  Google Scholar 

  72. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation. 2000;102(16):1906–11.

    PubMed  CAS  Google Scholar 

  73. Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, et al. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart. 2004;90(8):871–6.

    Article  PubMed  CAS  Google Scholar 

  74. Cornoldi A, Caminiti G, Marazzi G, Vitale C, Patrizi R, Volterrani M, et al. Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease. Int J Cardiol. 2010;142(1):50–5.

    Article  PubMed  Google Scholar 

  75. Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart. 2004;90(4):446–7.

    Article  PubMed  CAS  Google Scholar 

  76. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J. 2006;27(1):57–64.

    Article  PubMed  CAS  Google Scholar 

  77. Bidoggia H, Maciel JP, Capalozza N, Mosca S, Blaksley EJ, Valverde E, et al. Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone. Am Heart J. 2000;140(4):678–83.

    Article  PubMed  CAS  Google Scholar 

  78. Charbit B, Christin-Maitre S, Demolis JL, Soustre E, Young J, Funck-Brentano C. Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol. 2009;103(6):887–90.

    Article  PubMed  CAS  Google Scholar 

  79. Jonsson MK, Vos MA, Duker G, Demolombe S, van Veen TA. Gender disparity in cardiac electrophysiology: implications for cardiac safety pharmacology. Pharmacol Ther. 2010;127(1):9–18.

    Article  PubMed  CAS  Google Scholar 

  80. Malkin CJ, Morris PD, Pugh PJ, English KM, Channer KS. Effect of testosterone therapy on QT dispersion in men with heart failure. Am J Cardiol. 2003;92(10):1241–3.

    Article  PubMed  CAS  Google Scholar 

  81. Mayuga KA, Parker M, Sukthanker ND, Perlowski A, Schwartz JB, Kadish AH. Effects of age and gender on the QT response to exercise. Am J Cardiol. 2001;87(2):163–7.

    Article  PubMed  CAS  Google Scholar 

  82. Pecori Giraldi F, Toja PM, Filippini B, Michailidis J, Scacchi M, Stramba Badiale M, et al. Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study. Int J Androl. 2010;33(1):e132–8.

    Article  PubMed  CAS  Google Scholar 

  83. van Noord C, Dorr M, Sturkenboom MC, Straus SM, Reffelmann T, Felix SB, et al. The association of serum testosterone levels and ventricular repolarization. Eur J Epidemiol. 2010;25(1):21–8.

    Article  PubMed  CAS  Google Scholar 

  84. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–22.

    Article  PubMed  CAS  Google Scholar 

  85. Bremner WJ. Testosterone deficiency and replacement in older men. N Engl J Med. 2010;363(2):189–91.

    Article  PubMed  CAS  Google Scholar 

  86. Phillips GB. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(19):1866. author reply −7.

    PubMed  Google Scholar 

  87. Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95(2):639–50.

    Article  PubMed  CAS  Google Scholar 

  88. Meriggiola MC, Costantino A, Saad F, D’Emidio L, Morselli Labate AM, Bertaccini A, et al. Norethisterone enanthate plus testosterone undecanoate for male contraception: effects of various injection intervals on spermatogenesis, reproductive hormones, testis, and prostate. J Clin Endocrinol Metab. 2005;90(4):2005–14.

    Article  PubMed  CAS  Google Scholar 

  89. Kamischke A, Heuermann T, Kruger K, von Eckardstein S, Schellschmidt I, Rubig A, et al. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations. J Clin Endocrinol Metab. 2002;87(2):530–9.

    Article  PubMed  CAS  Google Scholar 

  90. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215–24.

    Article  PubMed  CAS  Google Scholar 

  91. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192–202.

    Article  PubMed  CAS  Google Scholar 

  92. Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA, J Am Med Assoc. 2006;296(19):2351–61.

    Article  CAS  Google Scholar 

  93. Page ST, Lin DW, Mostaghel EA, Marck BT, Wright JL, Wu J, et al. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial. J Clin Endocrinol Metab. 2011;96(2):430–7.

    Article  PubMed  CAS  Google Scholar 

  94. Idan A, Griffiths KA, Harwood DT, Seibel MJ, Turner L, Conway AJ, et al. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial. Ann Intern Med. 2010;153(10):621–32.

    PubMed  Google Scholar 

  95. Swerdloff RS, Wang C. Dihydrotestosterone: hormone or autocrine–paracrine signal? Ann Intern Med. 2010;153(10):678–9.

    PubMed  Google Scholar 

  96. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf). 1994;40(3):341–9.

    Article  CAS  Google Scholar 

  97. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci. 2005;60(11):1451–7.

    PubMed  Google Scholar 

  98. Wallace EM, Pye SD, Wild SR, Wu FC. Prostate-specific antigen and prostate gland size in men receiving exogenous testosterone for male contraception. Int J Androl. 1993;16(1):35–40.

    Article  PubMed  CAS  Google Scholar 

  99. Cooper CS, MacIndoe JH, Perry PJ, Yates WR, Williams RD. The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men. J Urol. 1996;156(2 Pt 1):438–41. discussion 41–2.

    PubMed  CAS  Google Scholar 

  100. Cooper CS, Perry PJ, Sparks AE, MacIndoe JH, Yates WR, Williams RD. Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol. 1998;159(2):441–3.

    Article  PubMed  CAS  Google Scholar 

  101. Amory JK, Bremner W. Endocrine regulation of testicular function in men: implications for contraceptive development. Mol Cell Endocrinol. 2002;186(2):205–9.

    CAS  Google Scholar 

  102. Kamischke A, Nieschlag E. Progress towards hormonal male contraception. Trends Pharmacol Sci. 2004;25(1):49–57.

    Article  PubMed  CAS  Google Scholar 

  103. Nieschlag E, Henke A. Hopes for male contraception. Lancet. 2005;365(9459):554–6.

    PubMed  Google Scholar 

  104. Page ST, Amory JK, Bremner WJ. Advances in male contraception. Endocr Rev. 2008;29(4):465–93.

    Article  PubMed  CAS  Google Scholar 

  105. Wang C, Swerdloff RS. Male hormonal contraception. Am J Obstet Gynecol. 2004;190(4 Suppl):S60–8.

    Article  PubMed  CAS  Google Scholar 

  106. von Eckardstein S, Noe G, Brache V, Nieschlag E, Croxatto H, Alvarez F, et al. A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J Clin Endocrinol Metab. 2003;88(11):5232–9.

    Article  CAS  Google Scholar 

  107. Attardi BJ, Engbring J, Gropp D, Hild SA. Development of Dimethandrolone 17{beta}-Undecanoate (DMAU) as an Oral Male Hormonal Contraceptive: Induction of Infertility and Recovery of Fertility in Adult Male Rabbits. J Androl. 2010.

  108. Attardi BJ, Hild SA, Reel JR. Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity. Endocrinology. 2006;147(6):3016–26.

    Article  PubMed  CAS  Google Scholar 

  109. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006;12(2):169–78.

    Article  PubMed  CAS  Google Scholar 

  110. Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, et al. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J Med Chem. 2009;52(12):3597–617.

    Article  PubMed  CAS  Google Scholar 

  111. Jones A, Hwang DJ, Narayanan R, Miller DD, Dalton JT. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology. 2010.

  112. Schmees N, Weinmann H. Recent patent trends in the field of progesterone receptor agonists and modulators. Expert Opin Ther Pat. 2009;19(11):1521–34.

    Article  PubMed  CAS  Google Scholar 

  113. Spitz IM. Progesterone receptor antagonists. Curr Opin Investig Drugs. 2006;7(10):882–90.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This review was supported by Endocrinology and Metabolism Training Grant (T32 DK007571), the General Clinical Research Center at Harbor UCLA (RR MO1 00425), and the NICHD through the Contraceptive Clinical Network Centers (Male Area) (HHSN275200403369I) to Los Angeles Biomedical Research Institute.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, 90509, USA

    Niloufar Ilani, Ronald S. Swerdloff & Christina Wang

  2. General Clinical Research Center, Harbor-UCLA Medical Center, 1000 W. Carson Street, Torrance, CA, 90509, USA

    Christina Wang

Authors
  1. Niloufar Ilani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald S. Swerdloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christina Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christina Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ilani, N., Swerdloff, R.S. & Wang, C. Male hormonal contraception: Potential risks and benefits. Rev Endocr Metab Disord 12, 107–117 (2011). https://doi.org/10.1007/s11154-011-9183-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-011-9183-3

Keywords

Search

Navigation