Review Article | Published:

The role of testosterone in erectile dysfunction

Nature Reviews Urology volume 7, pages 4656 (2010) | Download Citation

Abstract

Erectile dysfunction (ED) is a clinical disorder that results from a continuous spectrum of clinical factors, including physical illness (comprising the organic component of ED), reaction to stress (the intrapsychic component of ED) and relationship difficulties (the relationship component of ED). Testosterone clearly has a relevant role in all three causes of ED; the usefulness of this hormone in the treatment of ED has not, however, been completely clarified. The main physiological action of testosterone in the male sexual response is to regulate the timing of the erectile process as a function of sexual desire, thereby coordinating penile erection with sex. The link between ED, hypogonadism and underlying disorders (such as metabolic syndrome and type 2 diabetes mellitus) is nowadays well documented. The recognition of underlying disorders might be useful in motivating men with ED to improve their health-related lifestyle choices. Hence, patients with ED might be considered 'lucky', because their disorder offers the opportunity to undergo medical examinations to detect underlying disease. Both ED and hypogonadism are treatable conditions. A range of testosterone preparations are available for supplementation; their combination with phosphodiesterase 5 inhibitors might improve outcomes in some cases.

Key points

  • Testosterone levels can reflect perturbations in all three dimensions (organic, intrapsychic and relationship) of erectile dysfunction (ED)

  • Testosterone is important not only in controlling the mechanical process of penile erection, but it also controls male sexual behavior and attitudes

  • Testosterone replacement therapy (TRT) should be considered the first-line treatment in hypogonadal patients with ED

  • TRT monotherapy might not be adequate in all cases of ED because of the multifactorial pathophysiology of this disorder

  • In these cases, combination therapy with phosphodiesterase 5 inhibitors might improve outcomes

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References

  1. 1.

    , , , & Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J. Clin. Endocrinol. Metab. 94, 1853–1878 (2009).

  2. 2.

    et al. Age related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J. Sex. Med. doi:10.1111/j.1743-6109.2009.01601.x

  3. 3.

    [No authors listed] NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 270, 83–90 (1993).

  4. 4.

    et al. Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction. Int. J. Impot. Res. 15, 210–220 (2003).

  5. 5.

    , , & The dark side of testosterone deficiency: III. cardiovascular disease. J. Androl. 30, 477–494 (2009).

  6. 6.

    , , & Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases. Int. J. Androl. 32, 587–598 (2009).

  7. 7.

    , , & Obesity, low testosterone levels and erectile dysfunction. Int. J. Impot. Res. 21, 89–98 (2009).

  8. 8.

    , & Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone. Andrologia 40, 259–264 (2008).

  9. 9.

    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285, 2486–2497 (2001).

  10. 10.

    et al. Psycho-biologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur. Urol. 50, 595–604 (2006).

  11. 11.

    et al. ANDROTEST: a structured interview for the screening of hypogonadism in patients with sexual dysfunction. J. Sex. Med. 3, 706–715 (2006).

  12. 12.

    , & Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome. Aging Male 11, 193–199 (2008).

  13. 13.

    et al. Testosterone partially ameliorates metabolic profile and metabolic responsiveness to PDE5 inhibitors in an animal model of metabolic syndrome. J. Sex. Med. doi:10.1111/j.1743-6109.2009.01467.x

  14. 14.

    , , , & Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology 144, 4484–4491 (2003).

  15. 15.

    et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J. Clin. Endocrinol. Metab. 89, 5462–5468 (2004).

  16. 16.

    et al. Association of hypogonadism and type 2 diabetes in men attending an outpatient erectile dysfunction clinic. Int. J. Impot. Res. 18, 190–197 (2006).

  17. 17.

    et al. Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122–2125 (2000).

  18. 18.

    , , & Adipocyte accumulation in penile corpus cavernosum of the orchiectomized rabbit: a potential mechanism for veno-occlusive dysfunction in androgen deficiency. J. Androl. 26, 242–248 (2005).

  19. 19.

    et al. Which patients with sexual dysfunction are suitable for testosterone replacement therapy? J. Endocrinol. Invest. 30, 880–888 (2007).

  20. 20.

    & Testosterone and erectile dysfunction. J. Androl. 29, 593–604 (2008).

  21. 21.

    et al. The effect of androgen on nitric oxide synthase in the male reproductive tract of the rat. Fertil. Steril. 63, 1101–1107 (1995).

  22. 22.

    , & Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 136, 1495–1501 (1995).

  23. 23.

    , , & Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int. 83, 327–333 (1999).

  24. 24.

    et al. Testosterone and sexual activity. J. Endocrinol. Invest. 28 (3 Suppl.), 39–44 (2005).

  25. 25.

    et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J. Sex. Med. 3, 253–264 (2006).

  26. 26.

    , , & Improved erectile function after Rho-kinase inhibition in a rat castrate model of erectile dysfunction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R1572–R1579 (2003).

  27. 27.

    et al. Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes. J. Sex. Med. 4, 620–630 (2007).

  28. 28.

    et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145, 2253–2263 (2004).

  29. 29.

    et al. Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum. Eur. Urol. 47, 409–416 (2005).

  30. 30.

    et al. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140, 1861–1868 (1999).

  31. 31.

    , , & The relationship of serum testosterone to erectile function in normal aging men. J. Urol. 167, 1745–1748 (2002).

  32. 32.

    in Rome and China: Comparative Perspective Ancient World Empire (ed. Sheidel, W.) 83–89 (Oxford University Press, 2009).

  33. 33.

    Sexual differentiation of the brain and behavior. Best Pract. Res. Clin. Endocrinol. Metab. 21, 431–444 (2007).

  34. 34.

    The endocrinology of sexual arousal. J. Endocrinol. 186, 411–427 (2005).

  35. 35.

    , & The effects of exogenous testosterone on sexuality and mood of normal men. J. Clin. Endocrinol. Metab. 75, 1503–1507 (1992).

  36. 36.

    et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA Recommendations. Eur. Urol. 55, 121–130 (2009).

  37. 37.

    et al. Psycho-biological correlates of hypoactive sexual desire in patients with erectile dysfunction. Int. J. Impot. Res. 16, 275–281 (2004).

  38. 38.

    Hyperprolactinemia and sexual function in men: a short review. Int. J. Impot. Res. 15, 373–377 (2003).

  39. 39.

    et al. The impotent couple: low desire. Int. J. Androl. 28, 46–52 (2005).

  40. 40.

    et al. Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J. Sex. Med. 4, 1485–1493 (2007).

  41. 41.

    et al. Endocrine aspects of sexual dysfunction in men. J. Sex. Med. 1, 69–81 (2004).

  42. 42.

    et al. Prolactin-screening tumours and hypogonadism in 22 men. N. Engl. J. Med. 299, 847–852 (1978).

  43. 43.

    et al. PRL secreting adenomas in male patients. Pituitary 8, 39–42 (2005).

  44. 44.

    et al. Autoeroticism, mental health and organic disturbances in patients with erectile dysfunction. J. Sex. Med. doi:10.1111/j.1743-6109.2009.01497.x

  45. 45.

    et al. Psychobiological correlates of extramarital affairs and differences between stable and occasional infidelity among men with sexual dysfunctions. J. Sex. Med. 6, 666–675 (2009).

  46. 46.

    , & Multiple partners are associated with higher testosterone in North American men and women. Horm. Behav. 51, 454–459 (2007).

  47. 47.

    , & A multivariate analysis of female extramarital coitus. J. Marriage Fam. 37, 375–384 (1975).

  48. 48.

    & Sexual infidelity among married and cohabiting Americans. J. Marriage Fam. 62, 48–60 (2000).

  49. 49.

    , & The social endocrinology of dominance: basal testosterone predicts cortisol changes and behavior following victory and defeat. J. Pers. Soc. Psychol. 94, 1078–1093 (2008).

  50. 50.

    Testosterone and human aggression: an evaluation of the challenge hypothesis. Neurosci. Biobehav. Rev. 30, 319–345 (2006).

  51. 51.

    , & Effects of testosterone on mood, aggression, and sexual behavior in young men: a double-blind, placebo-controlled, cross-over study. J. Clin. Endocrinol. Metab. 89, 2837–2845 (2004).

  52. 52.

    & Testosterone and dominance in men. Behav. Brain Sci. 21, 353–363 (1998).

  53. 53.

    et al. Hysterical traits are not from the uterus but from the testis: a study in men with sexual dysfunction. J. Sex. Med. 6, 321–331 (2009).

  54. 54.

    et al. Impairment of couple relationship in male patients with sexual dysfunction is associated with overt hypogonadism. J. Sex. Med. 6, 2591–2600 (2009).

  55. 55.

    No authors listed] Effects of sexual activity on beard growth in man. Nature 226, 869–870 (1970).

  56. 56.

    et al. Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int. J. Androl. 22, 385–392 (1999).

  57. 57.

    et al. Sexual inactivity results in reversible reduction of LH bioavailability. Int. J. Impot. Res. 14, 93–99 (2002).

  58. 58.

    et al. Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels. Clin. Endocrinol. (Oxf.) 61, 382–386 (2004).

  59. 59.

    et al. A. Low serum bioactive luteinizing hormone in nonorganic male impotence: possible relationship with altered gonadotropin-releasing hormone pulsatility. J. Clin. Endocrinol. Metab. 67, 867–875 (1988).

  60. 60.

    et al. Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism. J. Sex. Med. 6, 1270–1283 (2009).

  61. 61.

    et al. Decreased pituitary–gonadal secretion in men with obstructive sleep apnea. J. Clin. Endocrinol. Metab. 87, 3394–3398 (2002).

  62. 62.

    et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 91, 1995–2010 (2006).

  63. 63.

    , , , & American Association of Clinical Endocrinologists. AACE Medical Guidelines for Clinical Practice for Evaluation and Treatment of Hypogonadism in Adult Male Patients—2002 Update. Endocr. Pract. 8, 440–446 (2002).

  64. 64.

    , & A critical evaluation of simple methods for the estimation of free testosterone in serum. J. Clin. Endocrinol. Metab. 84, 3666–3672 (1999).

  65. 65.

    , , , & Recognizing late-onset hypogonadism: a difficult task for sexual health care. J. Mens Health Gend. 6, 210–218 (2009).

  66. 66.

    , , & The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J. Androl. 30, 10–22 (2009).

  67. 67.

    et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 49, 1239–1242 (2000).

  68. 68.

    , , & Can results of the Aging Males' Symptoms (AMS) scale predict those of screening scales for androgen deficiency? Aging Male 7, 211–218 (2004).

  69. 69.

    , & Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men. Clin. Endocrinol. (Oxf.) 53, 703–711 (2000).

  70. 70.

    , , & Comparison of screening questionnaires for the diagnosis of hypogonadism. Maturitas 53, 424–429 (2006).

  71. 71.

    , & Advances in male hormone substitution therapy. Expert Opin. Pharmacother. 6, 1493–1506 (2005).

  72. 72.

    Testosterone replacement therapy for male hypogonadism: part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents. Int. J. Impot. Res. 19, 2–24 (2007).

  73. 73.

    , , & The latest options and future agents for treating male hypogonadism. Expert Opin. Pharmacother. 8, 2991–3008 (2007).

  74. 74.

    & Current and future testosterone delivery systems for treatment of the hypogonadal male. Expert Opin. Drug Deliv. 5, 471–481 (2008).

  75. 75.

    , , & in Testosterone: Action, Deficiency, Substitution, 3rd edn (eds Nieschlag, E. & Behre, H. M.) 405–444 (Cambridge University Press, 2004).

  76. 76.

    , & Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J. Urol. 164, 371–375 (2000).

  77. 77.

    , , & The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel. Eur. Urol. 47, 137–146 (2005).

  78. 78.

    & The relationship between hypogonadism and erectile dysfunction. Int. J. Impot. Res. 20, 231–235 (2008).

  79. 79.

    et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin. Endocrinol. (Oxf.) 63, 381–394 (2005).

  80. 80.

    & Significance of hypogonadism in erectile dysfunction. World J. Urol. 24, 657–667 (2006).

  81. 81.

    et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin. Proc. 82, 20–28 (2007).

  82. 82.

    Clinical practice: erectile dysfunction. N. Engl. J. Med. 357, 2472–2481 (2007).

  83. 83.

    , , & Sexual dysfunction in men and women with endocrine disorders. Lancet 369, 597–611 (2007).

  84. 84.

    , , & Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin. Endocrinol. (Oxf.) 14, 49–61 (1981).

  85. 85.

    et al. Effects of androgen treatment in impotent men with normal and low levels of free testosterone. Arch. Sex. Behav. 19, 223–234 (1990).

  86. 86.

    et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J. Clin. Endocrinol. Metab. 88, 2673–2681 (2003).

  87. 87.

    , , , & Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 63, 641–646 (2004).

  88. 88.

    et al. The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. Int. J. Androl. 32, 720–728 (2009).

  89. 89.

    , , & Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 6, 94–99 (2003).

  90. 90.

    et al. A novel therapy with testosterone and sildenafil for erectile dysfunction in patients on renal dialysis or after renal transplantation. J. Fam. Plann. Reprod. Health Care 30, 88–90 (2004).

  91. 91.

    , , , & Role of androgens in erectile function. J. Urol. 171, 2358–2362 (2004).

  92. 92.

    et al. Testosterone therapy can enhance erectile function response to sildenafil in patients with PADAM: a pilot study. J. Sex. Med. 2, 559–564 (2005).

  93. 93.

    et al. Does sildenafil combined with testosterone gel improve erectile dysfunction in hypogonadal men in whom testosterone supplement therapy alone failed? J. Urol. 173, 530–532 (2005).

  94. 94.

    , , , & Efficacy of sildenafil in male dialysis patients with erectile dysfunction unresponsive to erythropoietin and/or testosterone treatments. Int. J. Impot. Res. 18, 61–68 (2006).

  95. 95.

    , , & Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone. Int. J. Impot. Res. 18, 400–404 (2006).

  96. 96.

    , , , & Adjunctive use of AndroGel (testosterone gel) with sildenafil to treat erectile dysfunction in men with acquired androgen deficiency syndrome after failure using sildenafil alone. Urology 67, 571–574 (2006).

  97. 97.

    , & Testosterone and erectile function in hypogonadal men unresponsive to tadalafil: results from an open-label uncontrolled study. Andrologia 38, 61–68 (2006).

  98. 98.

    , , , & Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin. Endocrinol. (Oxf.) 58, 632–638 (2003).

  99. 99.

    , , & Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J. Urol. 172, 658–663 (2004).

  100. 100.

    , , , & Sildenafil improves sleep-related erections in hypogonadal men: evidence from a randomized, placebo-controlled, crossover study of a synergic role for both testosterone and sildenafil on penile erections. J. Androl. 27, 165–175 (2006).

  101. 101.

    et al. What is the threshold level of the PDE5 inhibitors' testosterone-dependence in men? A double blind placebo-controlled trial of testosterone gel addition in men with ED non responding to tadalafil 10 mg once a day alone [abstract #376]. Eur. Urol. Suppl. 8, 214 (2009).

  102. 102.

    , & Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur. Urol. 50, 940–947 (2006).

  103. 103.

    Smooth muscle cell calcium activation mechanisms. J. Physiol. 586, 5047–5061 (2008).

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Acknowledgements

We would like to thank Jacques Buvat (Director, Center d'Etude et de Traitement de la Pathologie de l'Appareil reproducteur et de la Psychosomatique [CETPARP], Lille, France) for his helpful collaboration during the preparation of the manuscript.

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  1. Sexual Medicine & Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy

    • Giovanni Corona
    •  & Mario Maggi

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The authors declare no competing financial interests.

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Correspondence to Mario Maggi.

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DOI

https://doi.org/10.1038/nrurol.2009.235

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