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Reversible Keimzelltoxizität nach aggressiver Chemotherapie bei Patienten mit Hodentumoren: Ergebnisse einer prospektiven Studie

Reversible germ cell toxicity after aggressive chemotherapy in patients with testicular cancer: Results of a prospective study

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Summary

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25–60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.

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Abbreviations

FSH:

Follikel stimulierendes Hormon

LH:

Luteinisierendes Hormon

P(SD)VB:

Chemotherapie mit Cisplatin (Standard-Dosierung) Vinblastin und Bleomycin

P(MH)VB:

Chemotherapie mit Cisplatin (mittelhohe Dosierung) Viblastin und Bleomycin

P(MH)EI:

Chemotherapie mit Cisplatin (mittelhohe Dosierung) Etoposid und Ifosfamid

SAS:

Statisticel Analysis System

BMDP:

Statisticel Software Program

HCG:

Humanes Choriongonadotropin

Literatur

  1. Amat P, Paniagua R, Nistal M, Martin A (1986) Mitosis in adult human Leydig cells. Cell Tissue Res 243:219–221

    Google Scholar 

  2. Berthelsen JG, Skakkebaek NE (1983) Gonadal function in men with testis cancer. Fertil Steril 399:68–75

    Google Scholar 

  3. Berthelson JG (1984) Sperm counts and serum folicle — stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer. Fertil Steril 41:281–286

    Google Scholar 

  4. Colditz GA, Willett WC, Stampler MJ, Rosner B, Speizer FE, Hennekens CH (1987) Menopause and the risk of coronary heart disease in women. N Engl J Med 316:1105–1110

    Google Scholar 

  5. Drasga RE, Einhorn LH, Williams SD, Patel DN, Stevens EE (1983) Fertility after chemotherapy for testicular cancer. J Clin Oncol 1:179–183

    Google Scholar 

  6. Eik-Nes KB (1975) Biosynthesis and secretion of testicular steroids. In: Hamilton DW, Greep RO (eds) Handbook of physiology, Sect 7; Endocrinology, Vol V: Male reproductive System. Williams and Wilkins, Baltimore, pp 95–116

    Google Scholar 

  7. Ettinger B, Genant HK, Cann CE (1985) Long-term estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 102:316–324

    Google Scholar 

  8. Fossa SD, Klepp O, Molne K, Aakvaag A (1982) Testicular function after unilateral orchiectomy for cancer and before further treatment. Int J Androl 5:179–184

    Google Scholar 

  9. Fossa SD, Ons S, Abyholm T, Norman N, Leob M (1985) Post-treatment fertility in patients with testicular cancer. Cancer 57:210–214

    Google Scholar 

  10. Fritz K, Weißbach L (1985) Sperm parameters and ejaculation before and afte operative treatment of patients with germ-cell testicular cancer. Fertil Steril 43:451–454

    Google Scholar 

  11. Heinemann C (1982) Morphometrische, histologische und enzym-histologische Untersuchungen am Hoden der Ratte nach Gabe von Ifosfamid. Inauguraldissertation, Bonn

    Google Scholar 

  12. Heymer B (1981) Hodenbiopsie zur Diagnostik von Fertilitätsstörungen. Münch med Wochenschr 123:481–844

    Google Scholar 

  13. Kießling M, Haselberger J, Struth B (1982) Fertilität und Sexualfunktion vor und nach Therapie. In: Weißbach L, Hildenbrand G (Hrsg) Register- und Verbundstudie für Hodentumoren — Bonn Ergebnisse einer prospektiven Untersuchung. Zuckschwerdt, München, S 366–377

    Google Scholar 

  14. Kretser de DM, Burger HG, Hudson B (1974) The relationship between germinal cells and serum FSH levels in males with infertility. J Clin Endocrinol Metab 38:787–793

    Google Scholar 

  15. Kretser de DM, Burger GH, Bremner WJ (1983) Control of FSH and LH secretion. Monogr Endocrinol 25:12–43

    Google Scholar 

  16. Kreuser ED, Altwein JE, Hartlapp JE, Egghart G, Gaus W, Schreml W (1985) Bulky germinal tumors: importance of residual disease. Eur Urol 11:163–169

    Google Scholar 

  17. Kreuser ED, Harsch U, Hetzel WD, Schreml W (1986) Chronic gonadal toxicity in patients with testicular cancer after chemotherapy. Eur J Cancer Clin Oncol 22:289–294

    Google Scholar 

  18. Kreuser ED, Xiros N, Hetzel WD, Heimpel H (1987) Reproductive and endocrine gonadal capacity in patients treated with COPP-chemotherapy für Hodgkin's disease. J Cancer Res Clin Oncol 113:260–266

    Google Scholar 

  19. Kreuser ED (1987) Inzidenz und Prognose reproduktiver und endokriner Funktionsstörungen nach kurativer zytostatischer Chemotherapie bei Patienten mit malignen Erkrankungen. Habilitationsschrift, Universität Ulm

  20. Kreuser ED, Hetzel WD, Heit W, Hoelzer D, Kurrle E, Xiros N, Heimpel H (1988) Reproductive and endocrine gonadal functions in adults following multidrug chemotherapy for acute lymphoblastic or undifferentiated leukemia. J Clin Oncol 6:588–592

    Google Scholar 

  21. Kuber W, Lunglmayr G, Seitz W, Grauthoff H, Weißbach L (1980) Fertilität bei Patienten mit Seminom des Hodens. Urologie A 19:272–275

    Google Scholar 

  22. Lange PH, Narayan P, Vogelzang NJ, Shafer RB, Kennedy BJ, Fraley EE (1983) Return of fertility after treatment for nonseminomatous testicular cancer: Changing concepts. J Urol 129:1131–1135

    Google Scholar 

  23. Lange PH, Narayan P, Fraley EE (1984) Fertility issues following therapy for testicular cancer. Semin Urol 4:264–274

    Google Scholar 

  24. Lauritzen C (1982) Das Klimakterium der Frau. Schering, Paris Frankfurt Berlin

    Google Scholar 

  25. Leitner SP, Bosl GJ, Bajorunas D (1986) Gonadal dysfunction in patients treated for metastatic germ cell tumors. J Clin Oncol 4:1500–1505

    Google Scholar 

  26. Lienert EA (1973) Verteilungsfreie Methoden in der Biostatistik, Teil I. Anton Hain, Königstein Meisenheim, S 200–203

    Google Scholar 

  27. Ragni G, Bestetti O, Santoro A, Viviani S, Di Pietro R, DeLauretis L (1985) Evaluation of semen and pituitary gonadotropin function in men with untreated Hodgkin's disease. Fertil Steril 43:927–930

    Google Scholar 

  28. Rister M, Müller AM, Gladtke E (1983) Kinder ehemaliger krebskranker Patienten. Dtsch Med Wochenschr 108:1137–1142

    Google Scholar 

  29. Schütte B (1984A) Hodenbiopsie bei Subfertilität. In: Schirren C, Holstein AF (Hrsg) Fortschritte der Andrologie 9. Grosse, Berlin, S 166–167

    Google Scholar 

  30. Schütte B (1984) Beziehungen zwischen der Spermatozoendichte bzw. den Keimzellen des Hodens und Hormonanalysen (speziell) FSH bei Patienten mit Oligozoospermie. Urologie A 23:334–337

    Google Scholar 

  31. Scott RS, Burger HG (1980) An inverse relationship exists between seminal plasma inhibin and serum follicle-stimulating hormone in man. J Clin Endocrinol Metab 52:796–803

    Google Scholar 

  32. Weißbach L, Lange CE, Rodermund OE, Zwicker H, Gropp A, Pothmann W (1974) Fertilitätsstörungen bei behandelten Hodentumorpatienten. Urologe A 13:80–85

    Google Scholar 

  33. Weißbach L, Bach D, Struth B (1978) Die Fertilitätsprognose bei Patienten mit geminalen Hodentumoren. In: Verhandlungen der Deutschen Gesellschaft für Urologie, 30. Tagung, S 128–132

  34. Weißbach L, Sommerhoff Ch, Struth B (1980) Aussagen zur Fertilität bei Patienten mit germinalen Hodentumoren. Extracta urologica 3:159–174

    Google Scholar 

  35. Weißbach L, Boedefeld EA, Hartlapp JH (1987) Prospektive Multizenter-Studien über nicht-seminomatöse Hodentumoren in Frühstadien. Bericht nach 4-jähriger Laufzeit. In: Verh Dt Krebsgesell Vol 6. Fischer, Stuttgart

    Google Scholar 

  36. World Health Organization (1979) Handbook for reporting results of cancer treatment. WHO offset publication, No 48, Geneva

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Die Untersuchungen wurden durch die Deutsche Krebshilfe unterstützt (M 16/86 He 3)

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Kreuser, E.D., Kurrle, E., Hetzel, W.D. et al. Reversible Keimzelltoxizität nach aggressiver Chemotherapie bei Patienten mit Hodentumoren: Ergebnisse einer prospektiven Studie. Klin Wochenschr 67, 367–378 (1989). https://doi.org/10.1007/BF01711264

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