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Impact of Androgen Deprivation on Male Sexual Function

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Sexual Function in the Prostate Cancer Patient

Part of the book series: Current Clinical Urology ((CCU))

Abstract

Introduction: The role of androgens in sexual function and in particular in erectile physiology remains controversial. The aim of this chapter is to review the preclinical and clinical data on the impact of androgen deprivation in male sexual functioning since androgen ablation is the main treatment option for men with advanced prostate cancer and a critical component of radiation therapy for localized prostate cancer.

Methods: Review of preclinical and clinical evidence on the role of androgens in sexual function.

Results: Preclinical data show that androgens regulate penile development, smooth muscle and neural integrity, fibroelastic properties, adipocyte accumulation and distribution, expression and activity of NOS and PDE5 resulting in a dose–response relationship between testosterone and erectile function. Clinical evidence documents the negative impact of androgen ablation on sexual desire and activity, nocturnal erections, and erectile function in a dose–response relationship. In addition, androgen replacement in men improves the effectiveness of PDE 5 inhibitors.

Conclusions: The literature supports that androgen ablation results in a decrease of sexual desire, nocturnal erections, erectile function, and overall sexual satisfaction. These observations are particularly important in men with prostate cancer, since androgen ablation is the main treatment option for men with advanced prostate cancer and a critical component of radiation therapy for localized prostate cancer.

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References

  1. Traish, A., and Kim, N. (2005 Nov) The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J. Sex. Med.2(6), 759–70.

    Article  PubMed  CAS  Google Scholar 

  2. Saenz de Tejada, I., Goldstein, I., Blanco, R., et al. (1985) Smooth muscle of the corpora cavernosae: role in penile erection. Surg. Forum. 36, 623–624.

    Google Scholar 

  3. de Groat, W.C., and Steers, W.D. (1988) Neuroanatomy and neurophysiology of penile erection. In: Tanagho, E.A., Lue, T.F., and McClue, R.D., eds. Contemporary Management of Impotence and Infertility. Baltimore: Williams & Wilkins, pp. 3–27.

    Google Scholar 

  4. Blanco, R., Saenz de Tejada, I., Goldstein, I., et al. (1988) Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis. Am. J. Physiol. 254, H468–H472.

    Google Scholar 

  5. Ignarro, L.J., Bush, P.A., Buga, G.M., et al. (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem. Biophys. Res. Comm. 170, 843–850.

    Article  PubMed  CAS  Google Scholar 

  6. Goldstein, I., Lue, T.F., Padma-Nathan, H. et al. (1998) Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N. Engl. J. Med. 338, 1397–1404.

    Article  PubMed  CAS  Google Scholar 

  7. Dorfman, R.I., and Shipley, R.A. (1956) Androgens: Biochemistry, Physiology, and Clinical Significance. New York: John Wiley & Sons, Inc.

    Google Scholar 

  8. Shen, R., Lin, M.C., Sadeghi, F., Swerdloff, R.S., Rajfer, J., and Gonzalez-Cadavid, N.F. (1996) Androgens are not major down-regulators of androgen receptor levels during growth of the immature rat penis. J. Steroid Biochem. Mol. Biol. 57, 301–313.

    Article  PubMed  CAS  Google Scholar 

  9. Gonzalez-Cadavid, N., Vernet, D., Fuentes, N.A., Rodriguez, J.A., Swerdloff, R.S., and Rajfer, J. (1993) Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis. Mol. Cell Endocrinol. 90, 219–229.

    Article  PubMed  CAS  Google Scholar 

  10. Lugg, J.A., Rajfer, J., and Gonzalez-Cadavid, N.F. (1995) Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 136, 1495–1501.

    Article  PubMed  CAS  Google Scholar 

  11. Seo, S.I., Kim, S.W., and Paick, J.S. (1999) The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat. Asian J. Androl. 1, 169–174.

    PubMed  CAS  Google Scholar 

  12. Choi, S.K., Han, S.W., Kim, D.H., and de Lignieres, B. (1993) Transdermal dihydrotestosterone therapy and its effects on patients with microphallus. J. Urol. 150, 657–660.

    PubMed  CAS  Google Scholar 

  13. Charmandari, E., Dattani, M.T., Perry, L.A., Hindmarsh, P.C., and Brook, C.G. (2001) Kinetics and effect of percutaneous administration of dihydrotestosterone in children. Horm. Res. 56, 177–181.

    Article  PubMed  CAS  Google Scholar 

  14. Saenz de Tejada I. (2002) Molecular mechanisms for the regulation of penile smooth muscle contractility. Int. J. Impot. Res. 14(Suppl 1):S6–S10.

    Google Scholar 

  15. Traish, A.M., Park, K., Dhir, V., Kim, N.N., Moreland, R.B., and Goldstein, I. (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140, 1861–1868.

    Article  PubMed  CAS  Google Scholar 

  16. Traish, A.M., Munarriz, R., O’Connell, L., Choi, S., Kim, S.W., Kim, N.N., Huang, Y.H., and Goldstein, I. (2003) Effects of medical and surgical castration on erectile function in an animal model. J. Androl. 24, 381–387.

    PubMed  Google Scholar 

  17. Rogers, R.S., Graziottin, T.M., Lin, C.M., Kan, Y.W., and Lue, T. (2003) Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus- mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int. J. Impot. Res. 15, 26–37.

    Article  PubMed  CAS  Google Scholar 

  18. Meusburger, S.M., and Keast, J.R. (2001) Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro. Neuroscience 108, 331–340.

    Article  PubMed  CAS  Google Scholar 

  19. Keast, J.R., Gleeson, R.J., Shulkes, A., and Morris, M.J. (2002) Maturational and maintenance effects of testosterone on terminal axon density and neuropeptide expression in the rat vas deferens. Neuroscience 112, 391–398.

    Article  PubMed  CAS  Google Scholar 

  20. Giuliano, F., Tostain, J., and Rossi, D. (2004) Testosterone and male sexuality: basic research and clinical data. Prog. Urol. 14, 783–790.

    PubMed  CAS  Google Scholar 

  21. Baba, K., Yajima, M., Carrier, S., Akkus, E., Reman, J., Nunes, L., Lue T.F., and Iwamoto, T. (2000a) Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Urology 56, 533–538.

    Article  PubMed  CAS  Google Scholar 

  22. Shabsigh, R., Kaufman, J.M., Steidle, C., and Padma-Nathan, H. (2004 Aug) 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(2), 658–663.

    Article  PubMed  CAS  Google Scholar 

  23. Jevtich, M., Khawand, N.Y., and Vidic, B. (1990) Clinical significance of ultrastructural findings in the corpus cavernosa of normal and impotent men. J. Urol. 143, 289–293.

    PubMed  CAS  Google Scholar 

  24. Nehra, A., Goldstein, I., Pabby, A., Nugent, M., Huang, Y.H., de las Morenas, A., Krane, R.J., Udelson, D., Saenz de Tejada, I., and Moreland, R.B. (1996) Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J. Urol. 156, 1320–1329.

    Google Scholar 

  25. Wespes, E., Schiffmann, S., Depierreux, M., Vanderhaegan, J.J., and Schulman, C.C. (1990) Is cavernovenous leakage related to a reduction of intracavernous smooth muscle fibers? Int. J. Impot. Res. 2, 30.

    Google Scholar 

  26. Traish, A.M., Toselli, P., Jeong, S.J., and Kim, N.N. (2005) 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.

    PubMed  Google Scholar 

  27. Bhasin, S., Taylor, W.E., Singh, R., Artaza, J., Sinha-Hikim, I., Jasuja, R., Choi, H., and Gonzalez-Cadavid, N.F. (2003) The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J. Gerontol. 58A, 1103–1110.

    CAS  Google Scholar 

  28. Singh, R., Artaza, J.N., Taylor, W.E., Gonzalez-Cadavid, N.F., and Bhasin, S. (2003) Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/ 2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144, 5081–5088.

    Article  PubMed  CAS  Google Scholar 

  29. Corradi, L.S., Goes, R.M., Carvalho, H.F., and Taboga, S.R. (2004) Inhibition of 5a-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate. Differentiation 72, 198–208.

    Article  PubMed  CAS  Google Scholar 

  30. Baba, K., Yajima, M., Carrier, S., Morgan, D.M., Nunes, L., Lue, T.F., and Iwamoto, T. (2000) Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibers and the erectile response in rat penis. BJU Int. 85, 953–958.

    Article  PubMed  CAS  Google Scholar 

  31. Lugg, J., Ng, C., Rajfer, J., and Gonzalez-Cadavid, N. (1996) Cavernosal nerve stimulation in the rat reverses castration-induced decrease in penile NOS activity. Am. J. Physiol. 271, E354–E361.

    PubMed  CAS  Google Scholar 

  32. Zvara, P., Sioufi, R., Schipper, H.M., Begin, L.R., and Brock, G.B. (1995) Nitric oxide mediated erectile activity is a testosterone dependent event: A rat erection model. Int. J. Impot. Res. 7, 209–219.

    PubMed  CAS  Google Scholar 

  33. Garban, H., Marquez, D., Cai, L., Rajfer, J., and Gonzalez-Cadavid, N.F. (1995) Restoration of normal adult penile erectile response in aged rats by long-term treatment with androgens. Biol. Reprod. 53, 1365–1372.

    Article  PubMed  CAS  Google Scholar 

  34. Penson, D.F., Ng, C., Cai, L., Rajfer, J., and Gonzalez-Cadavid, N.F. (1996) Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol. Reprod. 55, 567–574.

    Article  PubMed  CAS  Google Scholar 

  35. Penson, D.F., Ng, C., Rajfer, J., and Gonzalez-Cadavid, N.F. (1997) Adrenal control of erectile function and nitric oxide synthase in the rat penis. Endocrinology 138, 3925–3932.

    Article  PubMed  CAS  Google Scholar 

  36. Shen, Z., Chen, Z., Lu, Y., Chen, F., and Chen, Z. (2000) Relationship between gene expression of nitric oxide synthase and androgens in rat corpus cavernosum. Chin. Med. J. (Engl) 113, 1092–1095.

    CAS  Google Scholar 

  37. Marin, R., Escrig, A., Abreu, P., and Mas, M. (1999) Androgen dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol. Reprod. 61, 1012–1016.

    Article  PubMed  CAS  Google Scholar 

  38. Reilly, C.M., Zamorano, P., Stopper, V.S., and Mills, T.M. (1997) Androgenic regulation of NO availability in rat penile erection. J. Androl. 18, 110–115.

    PubMed  CAS  Google Scholar 

  39. Schirar, A., Bonnefond, C., Meusnier, C., and Devinoy, E. (1997) Androgens modulate nitric oxide synthase messenger ribonucleic acid expression in neurons of the major pelvic ganglion in the rat. Endocrinology 138, 3093–3102.

    Article  PubMed  CAS  Google Scholar 

  40. Park, K.H., Kim, S.W., Kim, K.D., and Paick, J.S. (1999) Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int. 83, 327–333.

    Article  PubMed  CAS  Google Scholar 

  41. Reilly, C.M., Stopper, V.S., and Mills, T.M. (1997) Androgens modulate the alpha-adrenergic responsiveness of vascular smooth muscle in the corpus cavernosum. J. Androl. 18, 26–31.

    PubMed  CAS  Google Scholar 

  42. Moreland, R.B., Goldstein, I., Kim, N.N., et al. (1999) Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: research and clinical implications in erectile dysfunction. Trends Endocrinol. Metab. 10, 97–104.

    Article  PubMed  CAS  Google Scholar 

  43. Morelli, A., Filippi, S., Mancina, R., Luconi, M., Vignozzi, L., Marini, M., Orlando, C., Vannelli, G.B., Aversa, A., Natali, A., Forti, G., Giorgi, M., Jannini, E.A., Ledda, F., and Maggi, M. (2004) Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145, 2253–2263.

    Article  Google Scholar 

  44. Zhang, X.H., Morelli, A., Luconi, M., Vignozzi, L., Filippi, S., Marini, M., Vannelli, G.B., Mancina, R., Forti, G., and Maggi, M. (2005) Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum. Eur. Urol. 47, 409–416.

    Article  PubMed  CAS  Google Scholar 

  45. Zhang, X.H., Morelli, A., Luconi, M., Vignozzi, L., Filippi, S., Marini, M., Vannelli, G.B., Mancina, R., Forti, G., and Maggi, M. (2005 Mar) Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in rat corpus cavernosum. Eur. Urol. 47(3), 409–416.

    Article  PubMed  CAS  Google Scholar 

  46. Armagan, A., Kim, N.N., Goldstein, I., and Traish, A.M. (2006 Jul–Aug) Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold. J. Androl. 27(4), 517–526.

    Article  PubMed  CAS  Google Scholar 

  47. Isidori, A.M., Giannetta, E., Gianfrilli, D., Greco, E.A., Bonifacio, V., Aversa, A., Isidori, A., Fabbri, A., and Lenzi, A. (2005 Oct) Effects of testosterone on sexual function in men: results of a meta-analysis. Clin. Endocrinol. (Oxford) 63(4), 381–394.

    Article  CAS  Google Scholar 

  48. Peters, C.A., and Walsh, P.C. (1987) The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia. N. Engl. J. Med. 317, 599–604.

    Article  PubMed  CAS  Google Scholar 

  49. Eri, L.M., and Tveter, K.J. (1994) Safety, side effects and patient acceptance of the luteinizing hormone releasing hormone agonist leuprolide in treatment of benign prostatic hyperplasia. J. Urol. 152, 448–452.

    PubMed  CAS  Google Scholar 

  50. Eri, L.M., and Tveter, K.J. (1994) Safety, side effects and patient acceptance of the antiandrogen Casodex in the treatment of benign prostatic hyperplasia. Eur. Urol. 26, 219–226.

    PubMed  CAS  Google Scholar 

  51. Rousseau, L., Dupont, A., Labrie, F., and Couture, M. (1988) Sexuality changes in prostate cancer patients receiving antihormonal therapy combining the antiandrogen flutamide with medical (LHRH agonist) or surgical castration. Arch. Sex. Behav. 17, 87–98.

    Article  PubMed  CAS  Google Scholar 

  52. Marumo, K., Baba, S., and Murai, M. (1999) Erectile function and nocturnal penile tumescence in patients with prostate cancer undergoing luteinizing hormone-releasing hormone agonist therapy. Int. J. Urol. 6, 19–23.

    Article  PubMed  CAS  Google Scholar 

  53. Kumamoto, Y., Yamaguchi, Y., Sato, Y., Suzuki, R., Tanda, H., Kato, S., Mori, K., Matsumoto, H., Maki, A., Kadono, M., et al. (1990) [Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate Part I: Nocturnal penile tumescence monitoring]. Hinyokika Kiyo. 36, 213–226.

    PubMed  CAS  Google Scholar 

  54. Bettocchi, C., Palumbo, F., Cormio, L., Ditonno, P., Battaglia, M., and Selvaggi, F.P. (2004) The effects of androgen depletion on human erectile function: a prospective study in male-to-female transsexuals. Int. J. Impot. Res. 16, 544–546.

    Article  PubMed  CAS  Google Scholar 

  55. Handelsman, D.J., and Zajac, J.D. (2004) Androgen deficiency and replacement therapy in men. Med. J. Aust. 180, 529–535.

    PubMed  Google Scholar 

  56. Mulhall, J.P., Valenzuela, R., Aviv, N., and Parker, M. (2004) Effect of testosterone supplementation on sexual function in hypogonadal men with erectile dysfunction. Urology 63, 348–353.

    Article  PubMed  Google Scholar 

  57. Greenstein, A., Plymate, S.R., and Katz, P.G. (1995) Visually stimulated erection in castrated men. J. Urol. 153, 650–652.

    Article  PubMed  CAS  Google Scholar 

  58. Christ-Crain, M., Mueller, B., Gasswer, T.C., Kraenzlin, M., Trummler, M., Huber, P., Meier, C. (2004) Is there a clinical relevance of partial androgen deficiency of the aging male? J. Urol. 172, 624–627.

    Article  PubMed  CAS  Google Scholar 

  59. Ojumu, A., and Dobs, A.S. (2003) Is hypogonadism a risk factor for sexual dysfunction. J. Androl.24, S46-S51.

    PubMed  Google Scholar 

  60. Kratzik, C.W., Schatzl, G., Lunglmayr, G., Rucklinger, E., and Huber, J. (2005) The impact of age, body mass index and testosterone on erectile dysfunction. J. Urol. 174, 240–243.

    Article  PubMed  Google Scholar 

  61. Svartberg, J. (2005) Should older men be treated with testosterone? Tidsskr. Nor. Laegeforen. 125, 879–882.

    PubMed  Google Scholar 

  62. Albrecht-Betancourt, M., Hijazi, R.A., and Cunningham, G.R. (2004) Androgen replacement in men with hypogonadism and erectile dysfunction. Endocrine 23, 143–148.

    Article  PubMed  CAS  Google Scholar 

  63. Carani, C., Granata, A.R., Bancroft, J., and Marrama, P. (1995) The effects of testosterone replacement on nocturnal penile tumescence and rigidity and erectile response to visual erotic stimuli in hypogonadal men. Psychoneuroendocrinology 20, 743–753.

    Article  PubMed  CAS  Google Scholar 

  64. Foresta, C., Coretta, N., Rosatto, M., Garolla, A., and Ferlin, A. (2004) Role of androgens in erectile function. J. Urol. 171, 2358–2362.

    Article  PubMed  CAS  Google Scholar 

  65. Schiavi, R.C., White, D., Mandeli, J., and Schreiner-Engel, P. (1993) Hormones and nocturnal penile tumescence in healthy aging men. Arch. Sex. Behav.22, 207–215.

    Article  PubMed  CAS  Google Scholar 

  66. Aversa, A., Isidori, A.M., De Martino, M.U., Caprio, M., Fabbrini, E., Rocchietti-March, M., Frajese, G., and Fabbri, A. (2000) Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin. Endocrinol. (Oxford) 53, 517–522.

    Article  CAS  Google Scholar 

  67. Aversa, A., Isidori, A.M., Spera, G., Lenzi, A., and Fabri, A. (2003) Androgens improve cavernous vasodilatation and response to sildenafil in patients with erectile dysfunction. Clin. Endo. 58, 632–638.

    Article  CAS  Google Scholar 

  68. Amar, E., Grivel, T., Hamidi, K., Lemaire, A., and Giuliano, F. (2005) Ageing men's sexual functions decline and the erectile dysfunction (ED) increase. Prog. Urol. 15, 6–9.

    PubMed  Google Scholar 

  69. Shamloul, R., Ghanem, H., Fahmy, I., El-Meleigy, A., Ashoor, S., Elnashaar, A., Kamel, I. (2005) Testosterone therapy can enhance erectile function response to sildenafil in patients with PADAM: a pilot study. J. Sex. Med. 2, 559–564.

    Article  PubMed  CAS  Google Scholar 

  70. Guay, A.T., Perez, J.B., Jacobson, J., and Newton, R.A. (2001) Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors. J. Androl. 22, 793–797.

    PubMed  CAS  Google Scholar 

  71. Zitzmann, M., Faber, S., and Nieschlag, E. (2006) Association of specific symptoms and metabolic risks with serum testosterone in older men. J. Clin. Endocrinol. Metab. 91, 4335–4343.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Associate Professor of Urology, Director of the Center for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, MA, USA

    Ricardo Munarriz

  2. Professor of Biochemistry, Departments of Biochemistry and Urology, Boston University School of Medicine, Boston, MA, USA

    Abdul Traish

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    Munarriz, R., Traish, A. (2009). Impact of Androgen Deprivation on Male Sexual Function. In: Mulhall, J. (eds) Sexual Function in the Prostate Cancer Patient. Current Clinical Urology. Humana Press. https://doi.org/10.1007/978-1-60327-555-2_11

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