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The effects of cancer and cancer treatments on male reproductive function

Nature Clinical Practice Urology volume 3, pages 312–322 (2006)Cite this article

Abstract

In male cancer patients, surgery, radiotherapy and chemotherapy can be followed by transient or permanent infertility by affecting ejaculatory or erectile function, or by impairing spermatogenesis. Cancer specialists should, therefore, discuss the impact of different therapies on fertility with their patients prior to treatment, and consider fertility-preserving measures before and during treatment, such as nerve-sparing operative techniques, adequate testicular shielding during radiotherapy and the avoidance of unnecessary gonadotoxic chemotherapy. Pretreatment sperm-cell cryopreservation should be offered, even in cases where the individual's risk of post-treatment infertility might seem minimal or if it might require testicular sperm-cell extraction. Samples that are severely oligospermic should also be cryopreserved. Post-treatment ejaculatory or erectile dysfunction can be reversed pharmacologically, but the success rate varies with the extent of neurologic sequelae of the treatments used. At present there is no established method to stimulate post-treatment impaired spermatogenesis, although currently available assisted reproductive techniques overcome some of the existing problems of infertility in cancer survivors, and ongoing research will hopefully increase these possibilities. A multidisciplinary approach that depends on close cooperation between relevant medical specialists is central to achieving such advances.

Key Points

  • Extensive pelvic or retroperitoneal surgery is often followed by erectile and/or ejaculatory dysfunction with subsequent fertility problems

  • Chemotherapy and infradiaphragmatic radiotherapy carry the risk of transiently or permanently impaired spermatogenesis

  • Semen cryopreservation should be offered to all men with cancer at risk of post-treatment infertility who are considering paternity

  • In males above the age of 12–13 years, mature sperm cells can be retrieved from the testes for cryopreservation by invasive procedures if they cannot be obtained by masturbation

  • Experimental approaches such as germ-cell transplantation and sperm-cell maturation in ectopic grafts sourced from testicular-tissue biopsies might enable very young patients to go on to become fathers

  • Future research with germ stem cells or embryonic stem cells will increase the number of options available for saving or restoring fertility in male cancer patients

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Figure 1: First post-treatment paternity (as recorded to the Medical Birth Registry of Norway) in 5,173 male cancer patients aged 15–45 years at diagnosis.
Figure 2: First post-treatment paternity in 554 testicular-cancer survivors who attempted post-treatment paternity, according to treatment.
Figure 3: First post-treatment paternity in survivors attempting post-treatment paternity after supradiaphragmatic radiotherapy for Hodgkin's lymphoma with (51 patients) and without (26 patients) chemotherapy.
Figure 4: Flow chart of preventive measures in the management of infertility in male cancer patients.
Figure 5: Flow chart of therapeutic measures in the management of infertility in male cancer patients.

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References

  1. Møller B et al. (2002) Prediction of cancer incidence in the Nordic countries up to the year 2020. Eur J Cancer Prev 11 (Suppl 1): S1–96

    PubMed  Google Scholar 

  2. Steliarova-Foucher E et al. (2004) Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study. Lancet 364: 2097–2105

    PubMed  Google Scholar 

  3. Landis SH et al. (1999) Cancer Statistics, 1999. Ca Cancer J Clin 49: 8–31

    CAS  PubMed  Google Scholar 

  4. Sant M et al. (2003) EUROCARE-3: survival of cancer patients diagnosed 1990–94—results and commentary. Ann Oncol 14 (Suppl 5): V61–V118

    PubMed  Google Scholar 

  5. Fosså SD et al. (2005) Parenthood in survivors after adulthood cancer and perinatal health in their offspring: a preliminary report. J Natl Cancer Inst Monogr 34: 77–82

    Google Scholar 

  6. Islam N and Trainer PJ (1998) The hormonal assessment of the infertile male. Br J Urol 82: 69–75

    CAS  PubMed  Google Scholar 

  7. Dohle GR et al. (2003) Androgens and male fertility. World J Urol 21: 341–345

    CAS  PubMed  Google Scholar 

  8. WHO (1992) WHO Laboratory manual for the examination of human semen and sperm-cervical mucus interactions, edn 3. Cambridge: Cambridge University Press

  9. Andersson AM et al. (2004) Serum inhibin B and follicle-stimulating hormone levels as tools in the evaluation of infertile men: significance of adequate reference values from proven fertile men. J Clin Endocrinol Metab 89: 2873–2879

    CAS  PubMed  Google Scholar 

  10. Klein EA (2000) Open technique for nerve-sparing retroperitoneal lymphadenectomy. Urology 55: 132–135

    CAS  PubMed  Google Scholar 

  11. Mirone V et al. (2003) Erectile dysfunction after surgical treatment. Int J Androl 26: 137–140

    PubMed  Google Scholar 

  12. Skakkebæk NE et al. (2001) Testicular dysgenesis syndrome: an increasingly common development disorder with encironmental aspects. Hum Reprod 16: 972–978

    PubMed  Google Scholar 

  13. Lim HN et al. (2001) Genetic analysis of the INSL3 gene in patients with maldescent of the testis. Eur Endocrinol 144: 129–137

    CAS  Google Scholar 

  14. Brehm R and Steger K (2005) Regulation of Sertoli cell and germ cell differentation. Adv Anat Embryol Cell Biol 181: 1–93

    CAS  PubMed  Google Scholar 

  15. Petersen PM et al. (1999) Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer. J Urol 161: 822–826

    CAS  PubMed  Google Scholar 

  16. Skakkebaek NE (1978) Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men. Histopathology 2: 157–170

    CAS  PubMed  Google Scholar 

  17. Raman JD et al. (2005) Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol 174: 1819–1822

    PubMed  Google Scholar 

  18. Berthelsen JG and Skakkebaek NE (1983) Gonadal function in men with testis cancer. Fertil Steril 39: 68–75

    CAS  PubMed  Google Scholar 

  19. Nakazumi H et al. (1996) Estrogen metabolism and impaired spermatogenesis in germ cell tumors of the testis. J Clin Endocrinol Metab 81: 1289–1295

    CAS  PubMed  Google Scholar 

  20. Rueffer U et al. (2001) Male gonadal dysfunction in patients with Hodgkin´s disease prior to treatment. Ann Oncol 12: 1307–1311

    CAS  PubMed  Google Scholar 

  21. Viviani S et al. (1991) Testicular dysfunction in Hodgkin`s disease before and after treatment. Eur J Cancer 27: 1389–1392

    CAS  PubMed  Google Scholar 

  22. Höbarth K et al. (1994) Incidence of antisperm antibodies in patients with carcinoma of the testis and in subfertile men with normogonadotropic oligoasthenoteratozoospermia. Urol Int 52: 162–165

    PubMed  Google Scholar 

  23. Fosså SD et al. (1984) Unilateral retroperitoneal lymph node dissection in patients with nonseminomatous testicular tumor in clinical stage I. Eur Urol 10: 17–23

    PubMed  Google Scholar 

  24. Montorsi F et al. (2004) Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol 45: 123–133

    PubMed  Google Scholar 

  25. Hollenbeck BK et al. (2003) Determinants of long-term sexual health outcome after radical prostatectomy measured by a validated instrument. J Urol 169: 1453–1457

    PubMed  Google Scholar 

  26. Havenga K et al. (2000) Avoiding long-term disturbance to bladder and sexual function in pelvic surgery, particularly with rectal cancer. Sem Surg Oncol 18; 235–243

    CAS  Google Scholar 

  27. Aus G et al. (2005) EAU Guidelines on prostate cancer. Eur Urol 48: 546–551

    CAS  PubMed  Google Scholar 

  28. Hobday TJ (2005) An overview of approaches to adjuvant therapy for colorectal cancer in the United States. Clin Colorectal Cancer 5 (Suppl 1): F11–F18

    Google Scholar 

  29. Shipley WU et al. (2005) Selective bladder preservation by trimodality therapy for patients with muscularis propria-invasive bladder cancer and who are cystectomy candidates—the Massachusetts general Hospital and Radiation Therapy Oncology Group experiences. Semin Radiat Oncol 15: 36–41

    PubMed  Google Scholar 

  30. Opjordsmoen S et al. (1994) Sexuality in patients treated for penile cancer: patients' experience and doctors' judgement. Br J Urol 73: 554–560

    CAS  PubMed  Google Scholar 

  31. Albers P et al. (2005) Guidelines on testicular cancer. Eur Urol 48: 885–894

    PubMed  Google Scholar 

  32. Petersen PM et al. (2002) Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis. J Clin Oncol 20: 1537–1543

    PubMed  Google Scholar 

  33. Budgell GJ et al. (2001) Prediction of scattered dose to the testes in abdominopelvic radiotherapy. Clin Oncol 13: 120–125

    CAS  Google Scholar 

  34. Hermann RM et al. (2005) Testicular dose and hormonal changes after radiotherapy of rectal cancer. Rad Onclol 75: 83–88

    CAS  Google Scholar 

  35. Mydlo JH and Lebed B (2004) Does brachytherapy of the prostate affect sperm quality and/or fertility in younger men? Scand J Urol Nephrol 38: 221–224

    PubMed  Google Scholar 

  36. Jacobsen KD et al. (1997) External beam abdominal radiotherapy in patients with seminoma stage I: field type, testicular dose, and spermatogenesis. Int J Radiat Oncol Biol Phys 38: 95–102

    CAS  PubMed  Google Scholar 

  37. Aass N et al. (1991) Prediction of long-term gonadal toxicity after standard treatment for testicular cancer. Eur J Cancer 27: 1087–1091

    CAS  PubMed  Google Scholar 

  38. Brydøy M et al. (2005) Paternity following treatment for testicular cancer. J Natl Cancer Inst 97: 1580–1588

    PubMed  Google Scholar 

  39. Huyghe E et al. (2004) Fertility after testicular cancer treatments. Cancer 100: 732–737

    PubMed  Google Scholar 

  40. Huddart RA et al. (2005) Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 93: 200–207

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Kinsella TJ et al. (1989) Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin`s disease. J Clin Oncol 7: 718–724

    CAS  PubMed  Google Scholar 

  42. Basavaraju SR and Easterly CE (2002) Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Med Phys 29: 2391–2403

    PubMed  Google Scholar 

  43. Potosky AL et al. (2004) Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Nat Cancer Inst 96: 1358–1367

    PubMed  Google Scholar 

  44. Falah M et al. (2005) Neuromuscular complications of cancer diagnosis and treatment. J Support Oncol 3: 271–282

    PubMed  Google Scholar 

  45. Socié G et al. (2003) Nonmalignant late effects after allogeneic stem cell transplantation. Blood 101: 3373–3385

    PubMed  Google Scholar 

  46. Hyer S et al. (2002) Testicular dose and fertility in men following I131 therapy for thyroid cancer. Clin Endocrinol 56: 755–758

    CAS  Google Scholar 

  47. Viviani S et al. (1985) Gonadal toxicity after combination chemotherapy for Hodgkin´s disease. Comparative results of MOPP vs ABVD. Eur J Cancer Oncol 21: 601–605

    CAS  Google Scholar 

  48. Lampe H et al. (1997) Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol 15: 239–245

    CAS  PubMed  Google Scholar 

  49. Donohue JP et al. (1990) Nervesparing retroperitoneal lymphadenectomy with preservation of ejaculation. J Urol 144: 287–292

    CAS  PubMed  Google Scholar 

  50. Shetty G and Meistrich ML (2005) Hormonal approaches to preservation and restoration of male fertility after cancer treatment. J Natl Cancer Inst Monogr 34: 36–39

    CAS  Google Scholar 

  51. Schrader M et al. (2003) “Onco-tese”: testicular sperm extraction in azoospermic cancer patients before chemotherapy—new guidelines? Urology 61: 421–425

    CAS  PubMed  Google Scholar 

  52. Magelssen H et al. (2005) Twenty years experience with semen cryopreservation in testicular cancer patients: who needs it? Eur Urol 48: 779–785

    CAS  PubMed  Google Scholar 

  53. Ragni G et al. (2003) Sperm banking and rate of assisted reproduction treatment: insights from a 15-year cryopreservation program for male cancer patients. Cancer 97: 1624–1629

    PubMed  Google Scholar 

  54. Sherins RJ et al. (1978) Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin´s disease. N Engl J Med 229: 12–16

    Google Scholar 

  55. Ben Arush MW et al. (2000) Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymohoma. Pediatr Hematol Oncol 17: 239–245

    CAS  PubMed  Google Scholar 

  56. Aslam I et al. (2000) Fertility preservation of boys undergoing anti-cancer therapy: a review of the existing situation and prospects for the future. Hum Reprod 15: 2154–2159

    CAS  PubMed  Google Scholar 

  57. Brougham MFH et al. (2003) Male fertility following childhood cancer: current concepts and future therapies. Asian J Androl 5: 325–337

    PubMed  Google Scholar 

  58. Rosenlund B et al. (1998) In-vitro fertilization and intracytoplasmic sperm injection in the treatment of infertility after testicular cancer. Hum Reprod 13: 414–418

    CAS  PubMed  Google Scholar 

  59. Schwarzer JU et al. (2003) Sperm retrieval procedures and intracytoplasmatic spermatozoa injection with epididymal and testicular sperms. Urol Int 70: 119–123

    PubMed  Google Scholar 

  60. Lombardo F et al. (2005) Androgens and fertility. J Endocrinol Invest 28 (Suppl 3): S51–S55

    Google Scholar 

  61. Kamischke A and Nieschlag E (2002) Update on medical treatment of ejaculatory disorders. Int J Androl 25: 333–344

    CAS  PubMed  Google Scholar 

  62. Damani MN et al. (2002) Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis tissue with intracytoplasmic sperm injection. J Clin Oncol 20: 930–936

    CAS  PubMed  Google Scholar 

  63. Orwig KE and Schlatt S (2005) Cryopreservation and transplantation of spermatogonia and testicular tissue for preservation of male fertility. J Natl Cancer Inst Monogr 34: 51–56

    Google Scholar 

  64. Radford JA et al. (1999) Fertility after treatment for cancer. BMJ 319: 935–936

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Geijsen N et al. (2004) Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature 427: 148–154

    CAS  Google Scholar 

  66. Meistrich ML and Shetty G (2003) Suppression of testosterone stimulates recovery of spermatogenesis after cancer treatment. Int J Androl 26: 141–146

    CAS  PubMed  Google Scholar 

  67. Byrne J et al. (1998) Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am J Hum Genet 62: 45–52

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Giwercman A (2003) Gonadotoxic cancer treatment in males—a reason for andrological counseling? Rad Oncol 68: 213–215

    Google Scholar 

  69. Mohr BA et al. (2005) Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts male ageing study. Clin Endocrinol 62: 64–73

    CAS  Google Scholar 

  70. Andersson AM et al. (1998) Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metab 83: 675–681

    CAS  PubMed  Google Scholar 

  71. Giwercman A and Petersen PM (2000) Cancer and male infertility. Baillieres Best Pract Res Clin Endocrinol Metab 14: 453–471

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Fellow,

    Henriette Magelssen & Sophie D Fosså

  2. at the Department of Clinical Cancer Research, Professor of Medical and Radiation Oncology at the University of Oslo, and chairs the Unit of Long-term Research on Outcomes After Cancer, Rikshospitalet–Radiumhospitalet Trust, Oslo, Norway

    Henriette Magelssen & Sophie D Fosså

  3. Research Fellow at the Institute of Medicine and Section of Oncology, Haukeland University Hospital, Bergen

    Marianne Brydøy

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Correspondence to Sophie D Fosså.

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Magelssen, H., Brydøy, M. & Fosså, S. The effects of cancer and cancer treatments on male reproductive function. Nat Rev Urol 3, 312–322 (2006). https://doi.org/10.1038/ncpuro0508

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