Advertisement

Andrologie

, Volume 5, Issue 4, pp 458–464 | Cite as

Chimiothérapie anticancéreuse et fertilité masculine

  • C. Chevreau
  • F. Huguet
Traitement Anticancereux, Fonction de Reprodution et Sexualtite

Resume

Parmi les agents anti-cancéreux, ceux qui interagissent directement avec l'ADN sont les plus toxiques pour les cellules de la lignée germinale. L'atteinte de ces cellules est essentiellement le fait des agents alkylants dont la toxicité est dose-dépendante. La rapidité et la qualité de récupération de la spermatogénèse est essentiellement fonction de la sévérité de l'atteinte des spermatogonies souches. Les études expérimentales conduites chez la souris et le rat ont permis de progresser dans la connaissance des mécanismes de la toxicité germinale des agents cytotoxiques, mais ces données ne sont pas toujours superposables à celles observées en clinique. Les études ont essentiellement été conduites chez les patients porteurs de tumeurs germinales du testicule ou de maladie de Hodgkin. Du fait de leur curabilité potentielle et de leur fréquente survenue chez le sujet jeune, elles représentent en effet les situations cliniques dans lesquelles il est essentiel d'essayer de préserver la fertilité du sujet. Le choix des protocoles chimiothérapiques les moins toxiques pour la lignée germinale, à résultat thérapeutique équivalent, est actuellement un moyen de réduire au maximum le risque d'azoospermie définitive. Ce risque n'est cependant jamais nul justifiant le recours systématique à l'auto-conservation de gamètes avant toute chimiothérapie chez un sujet susceptible de développer un projet de paternité.

Mots-clés

chimiothérapies alkylants fertilité mâle 

Cancer chemotherapy and fertility in men

Abstract

Among the chemotherapeutic drugs, those interacting with DNA are the more toxic for the germinal epithelium. Alkylating agents heavily affect these germ cells with a dose dependant toxicity. The incidence of recovery and length of time to recover normal spermatogenesis depend on the extent of damage to earlier forms of the germ cells. Experimental studies conducted on rodents improved the knowledge of the toxic mechanism of the drugs, which are in fact quite different of the clinical situation. Preservation of fertility is essential in hodgkin's disease and testis cancer because of their high curability rate and their incidence in young people.

Key words

chemotherapeutic drugs alkylants male fertility 

References

  1. 1.
    BERTHELSEN J.G., SKAKKEBAEK N.E.: Gonadal function in men with testis cancer. Fertil Steril, 1983, 39: 68–75.PubMedGoogle Scholar
  2. 2.
    BERTHELSEN J. G.: Testicular cancer and fertility. Int J Androl, 1987, 10: 371–380.PubMedCrossRefGoogle Scholar
  3. 3.
    BONNADONNA G., SANTORO A., VIVIANI S., et al: Treatment strategies for Hodgkin's disease. Semin Hematol, 1988, 25 (2): 51–57.Google Scholar
  4. 4.
    BRÄMSWING J.H., HEIMES U., HEIERMANN E., et al: The effects of different cumulative doses of chemotherapy on testicular function. Cancer, 1990, 65: 1298–1302.CrossRefGoogle Scholar
  5. 5.
    BUCHANAN J.D., FAIRLEY K.F., BARRIE J.U.: Return on spermatogenesis after stopping cyclophosphamide therapy. Lancet, 1972, 1: 568–569.Google Scholar
  6. 6.
    CHAPMAN R.M., STUCLIFFE S.B., REES L.H., et al: Cyclic combination chemotherapy and gonadal function. Reprospective study in males. Lancet, 1979, 1: 285–289.PubMedCrossRefGoogle Scholar
  7. 7.
    CHAPMAN R.M., SUTCLIFFE S.M., MALPAS J.C.: Male gonadal dysfunction in Hodgkin's disease. A prospective study. JAMA, 1981, 245: 1323–1328.PubMedCrossRefGoogle Scholar
  8. 8.
    CHEVIAKOFF S., CALAMERA J.C., MORGENFELD M., et al: Recovery of spermatogenesis in patients with lymphoma after treatment with chlorambucil. J Reprod Fertil, 1973, 33: 155–157.PubMedCrossRefGoogle Scholar
  9. 9.
    COSTABILE R.A.: The effects of cancer and cnacer therapy on male reproductive function. J Urol, 1993, 149: 1327–1330.PubMedGoogle Scholar
  10. 10.
    DA CUNHA M.F., MEISTRICH M.L., RIED H.L., et al: Active sperm production after cancer chemotherapy with doxorubicin. J Urol, 1983, 130: 927–930.PubMedGoogle Scholar
  11. 11.
    da CUNHA M.F., MEISTRICH M.L., FULLER L.M., et al: Recovery of spermatogenesis after treatment of Hodgkin's disease: limiting dose of MOPP chemotherapy. J Clin Oncology, 1984, 2: 571–577.Google Scholar
  12. 12.
    FAIRLEY K.F., BERRIE J.U., JONHSON W.: Sterility and testicular atrophy related to cyclophosphamide therapy. Lancet, 1972, 1: 568–569.PubMedCrossRefGoogle Scholar
  13. 13.
    FOSSA S.D., KLEPP O., AAKVAAG A., et al: Testicular function after combined chemotherapy for metastatic testicular cancer. Int J Androl, 1980, 3: 59–65.PubMedCrossRefGoogle Scholar
  14. 14.
    FOSSA S.D., OUS S., ABYHOLM T., et al: Post treatment fertility in patients with testicular cancer. I Influence of retroperitoneal lymph node dissection on ejaculatory potency. Br J Urol, 1985, 57: 204–209.PubMedCrossRefGoogle Scholar
  15. 15.
    FOSSA S.D., OUS S., ABYHOLM T., et al: Post treatment fertility in patients with testicular cancer. II Influence of cis-platin based combination chemotherapy and of retroperitoneaal surgery on hormone and sperm cell production. Br J Urol, 1985, 57: 210–214.PubMedCrossRefGoogle Scholar
  16. 16.
    HANSEN S.W., BERTHELSEN J.C., von der MAASE H.: Long term fertility and Leydig cell function in patients treated for germ cell cancer with cisplatin, vinblastine, and bleomycin versus surveillance. J Clin Oncology, 1990, 8: 1695–1698.Google Scholar
  17. 17.
    KOPF-MAIER P.: Effects of carboplatin on the testis. A histological Study. Cancer Chemotherapy Pharmacol, 1992, 29 (3): 227–235.CrossRefGoogle Scholar
  18. 18.
    KREUSER E.D., HARSCH U., HETZEL W.D., et al: Chronic gonadal toxicity in patients with testicular cancer after chemotherapy. Eur J Cancer Clin Oncology, 1986, 22: 289–294.CrossRefGoogle Scholar
  19. 19.
    KREUSER E.D., XIROS N., HETZEL W.D., et al: Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. J Cancer Res Clin Oncology, 1987, 113: 260–266.CrossRefGoogle Scholar
  20. 20.
    LEITNER S.P., BOSL G.L., BAJOURNAS D.: Gonadal dysfunction in patients treated for metastatic germ cell tumors. J Clin Oncology, 1986, 4: 1500–1505.Google Scholar
  21. 21.
    MARINA S., BARCELO P.: Permanent sterility after immunosuppressive therapy. Int J Androl, 1979, 2: 6–13.CrossRefGoogle Scholar
  22. 22.
    MARTIN du PAN R.C., CAMPANA A.: Physiopathology of spermatogenic arrest. Fertil-Steril, 1993 Déc, 60 (6): 937–946.PubMedGoogle Scholar
  23. 23.
    MEISTRICH M.L., FINCH M., da CUNHA M.F., et al: Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res, 1982, 42: 122–131.PubMedGoogle Scholar
  24. 24.
    MEISTRICH M.L.: Relation ship between spermatogonial stem cell survival and testis fucntion after cytotoxic therapy. Br J Cancer, 1986, 53 (suppl VII): 89–101.Google Scholar
  25. 25.
    MEISTRICH M.L., CHAWLA S.P., da CUNHA M.F., et al: Recovery of sperm production after for chemotherapy osteosarcoma. Cancer, 1989, 63: 2115–2123.PubMedCrossRefGoogle Scholar
  26. 26.
    MEISTRICH M.L.: Effects of chemotherapy and radiotherapy on spermatogenesis. Eur Urol, 1993, 23: 136–142.PubMedGoogle Scholar
  27. 27.
    NIJMAN J.M., SCHRAFFORDT K.H., KREMER J., et al: Gonadal function after surgery and chemotherapy in men with stage II and III non seminomatous testicular tumors. J Clin Oncology, 1987, 5: 651–666.Google Scholar
  28. 28.
    PRYSANT R.M., MEISTRICH M.L., WILSON G.W., et al: Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-hodgkin's lymphomas. J Clin Oncol, 1993, 11 (2): 239–247.Google Scholar
  29. 29.
    QURESHI M.A., GOLDSMITH H.J., PENNINGTON J.H., et al: Cyclophosphamide therapy and sterility. Lancet, 1972, ii: 1290–1291.CrossRefGoogle Scholar
  30. 30.
    RICHTER P., CALAMERA J.C., MARGENFELD M.C., et al: Effects of chlorambucil on spermatogenesis in the human with malignant lymphoma. Cancer, 1970, 23: 1026–1030.CrossRefGoogle Scholar
  31. 31.
    ROESER H.P., STOCKS A.E., SMITH A.J.: Testicular damage due to cytoloxic drugs and recovery after cessation of therapy. Aust NZ J Med, 1978, 8: 250–254.Google Scholar
  32. 32.
    ROTH B.J., GREIST A., KUBILIS P.S., et al: Cisplatin-base combination chemotherapy for disseminated germ cell tumors; long term follow-up. J Clin Oncology, 1988, 6: 1239–1247Google Scholar
  33. 33.
    SHAMBERGER R.G., ROSENBERG S.A., SIEPP C.A., et al: Effects of high dose metotrexate and vincristine on ovarian and testicular functions in patients undergoing postoperative adjuvant treatment of osteosarcoma. Cancer Treat Rep, 1981, 65: 739–746.PubMedGoogle Scholar
  34. 34.
    SHERINS R.J.: Gonadal Dysfunction. in Principes and practice of Oncology, V.T. de VITA, Lippincott Ed. Fourth edition, 1993: pp 2395–2404.Google Scholar
  35. 35.
    TSENG A., KESSLER R., FREIHA F., et al: Male fertility before and after treatment of testicular cancer (abstr). Proc Am Soc Clin Oncology, 1984, 24: 161.Google Scholar
  36. 36.
    VILAR O.: Effects of cytostatic drugs on human testicular function. in: Male fertility and sterility, MANCINI R.E., MARTINI L.; Edition Academic Press, 1974: pp 423–440.Google Scholar
  37. 37.
    VIVIANI S., SANTORO A., RAGNI G., et al: Gonadal toxicity after combination chemotherapy for Hodgkin's disease comparative results of MOPP versus ABVD. Eur J Cancer Clin Oncology, 1985, 21 (5): 601–605.CrossRefGoogle Scholar
  38. 38.
    WAXMAN J.H.X., TERRY Y.A., WRIGLEY P.F.M., et al: Gonadal function in Hodgkin's disease: long term follow up of chemotherapy. Br Med J, 285: 1612–1613.Google Scholar
  39. 39.
    WHITEHEAD E., SHALET S.M., BLACKLEDGE G., et al: The effects of Hodgkin's disease and combination chemotherapy on gonodal function in the adulte male. Cancer, 1982, 49: 418–422.PubMedCrossRefGoogle Scholar

Copyright information

© Société d’Andrologie de Langue Française 1995

Authors and Affiliations

  • C. Chevreau
    • 1
  • F. Huguet
    • 2
  1. 1.Département d'Oncologie MédicaleCentre Claudius Regaud 20Toulouse
  2. 2.Service d'HématologieClinique Dieulafoy Hôpital de PurpanToulouse

Personalised recommendations