Skip to main content

The effects of testosterone on the cavernous tissue and erectile function

Summary

A review of the current literature is conducted to explore the developmental aspects, animal and human experiences and the effects of pharmacological manipulation to explain the role androgens play in sexual function with special emphasis on erectile function and the erectile tissue. This review reveals that androgens are necessary for the normal development of the penis and their deficiency results in significant structural abnormalities. Although androgen receptors in the penis decrease after puberty, they usually do not disappear completely. Animal data show that androgens support erectile function through a direct effect on the erectile tissue. Experimental castration results in impaired erectile response to central and peripheral stimulation and decrease in penile tissue concentration of nitric oxide synthase-containing nerves. Testosterone replacement reverses these abnormalities. In the rat penis, apoptosis is induced by castration and new DNA synthesis is induced by testosterone replenishment. Human data are less clear than animal data. Castration results in loss of libido and in erectile dysfunction. However, these effects are not universal. Testosterone enhances libido, frequency of sexual acts and sleep-related erections. Its effects on erotic erections are not clear.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Baba K, Yajima M, Carrier S, Nagaraju P, Morgan DM, Ekkus E, Rehman J, Nunez L, Lue TF (1995) Effects of testosterone on the number of NADPH-diaphorase-staining nerve fibers in the rat corpus cavernosum and dorsal nerve. J Urol 153: 506A

    Google Scholar 

  2. 2.

    Bancroft J, Wu FC (1983) Changes in erectile responsiveness during androgen replacement therapy. Arch Sex Behav 12: 59

    PubMed  Google Scholar 

  3. 3.

    Bandyk MG, Sawczuk IS, Olsson CA, Katz AE, Buttyan R (1990) Characterization of the products of a gene expressed during androgen-programmed cell death and their potential use as a marker for urogenital injury. J Urol 143: 407–413

    PubMed  Google Scholar 

  4. 4.

    Baskin HJ (1983) Endocrinologic evaluation of impotence. South Med J 82: 446

    Google Scholar 

  5. 5.

    Bradshaw WG, Baum MJ, Awh CC (1981) Attenuation by 5alpha-reductase inhibitor of the activational effect of testosterone propionate on penile erections in castrated male rats. Endocrinology 109: 1047–1051

    PubMed  Google Scholar 

  6. 6.

    Buttyan R, Olsson CA, Pintar J, Chang C, Bandyk M, Ng P-Y, Sawczuk IS (1989) Induction of the TRPM 2 gene in cells undergoing programmed cell death. Mol Cell Biol 9: 3473–3481

    PubMed  Google Scholar 

  7. 7.

    Cher ML, Shinohara K, Breslin J, Vapnek J, Carroll PR (1995) High failure rate associated with long-term follow up of neoadjuvant androgen deprivation followed by radical prostatectomy for stage C prostate cancer. Br J Urol 75: 771–777

    PubMed  Google Scholar 

  8. 8.

    Choi SK, et al (1993) Transdermal dihydrotestosterone therapy and its effects on patients with microphallus. J Urol 150: 657

    PubMed  Google Scholar 

  9. 9.

    Colombel M, Olsson CA, Ng P-Y, Buttyan R (1992) Hormoneregulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle. Cancer Res 52: 4313–4319

    PubMed  Google Scholar 

  10. 10.

    Cunningham GR, et al. (1982) The relationship between serum testosterone and prolactin levels and nocturnal penile tumescence (NPT) in impotent men. J Androl 3: 241

    Google Scholar 

  11. 11.

    Davidson JM, Camargo CA, Smith ER (1979) Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab 48: 955–958

    PubMed  Google Scholar 

  12. 12.

    Delaere KPJ, Van Thillo EL (1991) Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. Semin Oncol 18: 13–18

    PubMed  Google Scholar 

  13. 13.

    Ellis WJ, and Grayhack JT (1963) Sexual function in aging males after orchiectomy and estrogen therapy. J Urol 89: 895

    Google Scholar 

  14. 14.

    Feldman KW, Smith DW (1975) Fetal phallic growth and penile standards for newborn male infants. J Pediatr 86: 395

    PubMed  Google Scholar 

  15. 15.

    Fenwick PBC, et al (1986) Nocturnal penile tumescence and serum testosterone levels. Arch Sex Behav 15: 12

    Google Scholar 

  16. 16.

    Fleshner NE, Trachtenberg J (1993) Treatment of advanced prostate cancer with the combination of finasteride plus flutamide: early results. Eur Urol 24[Suppl 2]: 106–111

    Google Scholar 

  17. 17.

    Frajese G, Lazzari R, Magnani A, Moretti A, Sforzi C, Nerozzi D (1990) Neurotransmitter, opiodergic system, steroid-hormone interaction and involvement in the replacement therapy of sexual disorders. J Steroid Biochem Mol Biol 37: 411

    PubMed  Google Scholar 

  18. 18.

    Friedman DE, et al (1986) Should impotent males who have no clinical evidence of hypogonadism have routine endocrine screening? Lancet I: 1041

    Google Scholar 

  19. 19.

    Geneser F (1986) Textbook of histology. Munksgaard, Copenhagen; p 644

    Google Scholar 

  20. 20.

    Godec CJ, Bates H, Labrosse K (1985) Testosterone receptors in corpora cavernosa of penis. Urology 26: 237

    PubMed  Google Scholar 

  21. 21.

    Goldman BD, et al (1972) Modification of phallus development and sexual behavior in rats treated with gonadotropin antiserum neonatally. Endocrinology 90: 1025

    PubMed  Google Scholar 

  22. 22.

    Guthrie RD, Smith DW, Graham CB (1973) Testosterone treatment for micropenis during early childhood. J Pediatr 83: 247

    PubMed  Google Scholar 

  23. 23.

    Hart BJ (1967) Testosterone regulation of sexual reflexes in spinal male rats. Science 155: 1283–1284

    PubMed  Google Scholar 

  24. 24.

    Hart BJ, Wallach SJ, Melese-D'Hopital PY (1983) Differences in responsiveness to testosterone of penile reflexes and copulatory behavior of male rats. Horm Behav 17: 274–283

    PubMed  Google Scholar 

  25. 25.

    Heaton JPW, Varrin SJ (1994) Effects of castration and exogenous testosterone supplementation in an animal model of penile erection. J Urol 151: 797–800

    PubMed  Google Scholar 

  26. 26.

    Heim N (1981) Sexual behavior of castrated sex offenders. Arch Sex Behav 10: 11

    PubMed  Google Scholar 

  27. 27.

    Immergut M, et al (1971) The local application of testosterone cream to the prepubertal phallus. J Urol 105: 905

    PubMed  Google Scholar 

  28. 28.

    Johansson JE, Anderson SO, Beckman KW, Lingardh C, Zador G (1987) Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate. Urology 29: 55–59

    PubMed  Google Scholar 

  29. 29.

    Johnson AR III, Jarow JP (1992) Is routine endocrine testing of impotent men necessary? J Urol 147: 1542

    PubMed  Google Scholar 

  30. 30.

    Kozlowski JM, Grayhack IT (1987) Carcinoma of the prostate. In: Gillenwater JY, Grayhack IT, Howards SS, Duckett JW (eds) Adult and pediatric urology, vol 34. YBMP, Chicago, pp 1126–1219

    Google Scholar 

  31. 31.

    Kwan M, Greenleaf W, et al (1983) The nature of androgen action on male sexuality: a combined laboratory self report study on hypogonadal men. J Clin Endocrinol Metab 57: 557–562

    PubMed  Google Scholar 

  32. 32.

    Kyprianou N, Isaacs IT (1988) Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122:552–562

    PubMed  Google Scholar 

  33. 33.

    Lange JD, et al (1980) Serum testosterone concentration and penile tumescence changes in men. Horm Behav 14: 267

    PubMed  Google Scholar 

  34. 34.

    Leedy MG, Beattie MS, Bresnahan JC (1987) Testosteroneinduced plasticity of synaptic inputs to adult mammalian motoneurons. Brain Res 424: 386–390

    PubMed  Google Scholar 

  35. 35.

    Lugg JA, Rajfer J, Gonzalez-Cadavid NF (1995) Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 136: 1495–1501

    PubMed  Google Scholar 

  36. 36.

    Luisi M, Franchi F (1980) Double blind group comparative study of testosterone undecanoate and mesterolone in hypogonadal male patients. J Endocrinol Invest 3: 305

    Google Scholar 

  37. 37.

    Lund F, Rasmussen F (1988) Flutamide versus stilbestrol in the management of advanced prostate cancer. A controlled prospective study. Br J Urol 61: 140–142

    PubMed  Google Scholar 

  38. 38.

    Maatman TJ, Montague DK (1986) Routine endocrine screening in impotence. Urology 27: 499

    PubMed  Google Scholar 

  39. 39.

    Matsumoto A, Arnold AP, Zampighi GA, Micevych PE (1988) Androgenic regulation of gap junctions between motoneurons in the rat spinal cord. J Neurosci 8: 4177–4183

    PubMed  Google Scholar 

  40. 40.

    McClure RD (1988) Endocrine evaluation and therapy of erectile dysfunction. Urol Clin North Am 15: 53–64

    PubMed  Google Scholar 

  41. 41.

    Meisel RL, O'Hanlon JK, Sachs BD (1984) Differential maintenance of penile responses and copulatory behavior by gonadal hormones in castrated male rats. Horm Behav 18: 56–64

    PubMed  Google Scholar 

  42. 42.

    Meyaard MJ, Otto SA, Jonker RR, Mijnster MJ, Keet RP, Miedema F (1992) Programmed death of T-cells in HIV-1 infection. Science 257: 217–219

    PubMed  Google Scholar 

  43. 43.

    Mills MT, Wiedmeier VT, Stopper VS (1992) Androgen maintenance of erectile function in the rat penis. Biol Reprod 46: 342–348

    PubMed  Google Scholar 

  44. 44.

    Muller SC, Hsieh JT, Lue TF, Tanagho EA (1988) Castration and erection: an animal study. Eur Urol 15: 118–124

    PubMed  Google Scholar 

  45. 45.

    Mulligan T, Schmitt B (1993) Testosterone for erectile failure, clinical review. J Gen Intern Med 8: 517–521

    PubMed  Google Scholar 

  46. 46.

    Nickel JC, et al (1984) Endocrine dysfunction in impotence: incidence, significance and cost-effective screening. J Urol 132: 40

    PubMed  Google Scholar 

  47. 47.

    Nonomura K, et al (1990) Androgen binding activity in the spongy tissue of mammalian penis. J Urol 144: 52

    Google Scholar 

  48. 48.

    O'Carroll R, Bancroft J (1985) Effects of androgen replacement on sexual behaviour and nocturnal erections in hypogonadal men. Clin Endocrinol 23: 527

    Google Scholar 

  49. 49.

    Proscar (1996) Information package insert

  50. 50.

    Rajfer J, Namkung PC, Petra PH (1980) Identification, partial characterization and age-related changes of a cytoplasmic androgen receptor in the rat penis. J Steroid Biochem 13: 1489

    PubMed  Google Scholar 

  51. 51.

    Raymond J, Miller M, Olsson CA, O'Toole K, Buttyan R, Shabsigh R (1996) Androgen induction of DNA synthesis in the rat penis. J Urol (in press)

  52. 52.

    Rubin HB, et al (1979) The relationship between men's endogenous levels of testosterone and their penile responses to erotic stimuli. Behav Res Ther 17: 305

    PubMed  Google Scholar 

  53. 53.

    Santarosa R, Te AE, Colombel MC, Koo HP, Olsson CA, Buttyan R, Shabsigh R (1996) Induction of apoptosis in the rat penis after castration. J Urol (in press)

  54. 54.

    Schiavi RC, White D (1976) Androgen and male sexual function: a review of human studies. J Sex Marital Ther 2: 214

    PubMed  Google Scholar 

  55. 55.

    Shabsigh R (1993): Medication related impotence. Contemp Urol 5: 51–61

    Google Scholar 

  56. 56.

    Shah RS, et al (1988) Hypothalamic-hypophyseal-testicular abnormalities and erectile dysfunction. Arch Androl 20: 137

    PubMed  Google Scholar 

  57. 57.

    Skakkeback NE, Bancroft J, et al (1983) Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin Endocrinol 14: 49–61

    Google Scholar 

  58. 58.

    Slag MF, et al (1983) Impotence in medical clinic outpatients. JAMA 249: 1736

    PubMed  Google Scholar 

  59. 59.

    Sogani PC, Vagaiwala MR, Whitmore WF (1984) Experience with flutamide in patients with advanced prostatic cancer without prior endocrine therapy. Cancer 54: 744–750

    PubMed  Google Scholar 

  60. 60.

    Spark RF, White RA, Connolly PB (1980) Impotence is not always psychogenic. Newer insights into hypothalamic-pituitary-gonadal dysfunction. JAMA 243: 750

    PubMed  Google Scholar 

  61. 61.

    Takane KK, Husmann DA, McPhaul MJ, Wilson JD (1991) Androgen receptor levels in the rat penis are controlled differently in distinctive cell types. Endocrinology 128: 224

    Google Scholar 

  62. 62.

    Walsh PC, et al (1978) Clinical and endocrinological evaluation of patients with congenital microphallus. J Urol 120: 90

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to R. Shabsigh.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shabsigh, R. The effects of testosterone on the cavernous tissue and erectile function. World J Urol 15, 21–26 (1997). https://doi.org/10.1007/BF01275152

Download citation

Keywords

  • Nitric Oxide
  • Testosterone
  • Androgen
  • Androgen Receptor
  • Sexual Function