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.
Similar content being viewed by others
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
Amat P, Paniagua R, Nistal M, Martin A (1986) Mitosis in adult human Leydig cells. Cell Tissue Res 243:219–221
Berthelsen JG, Skakkebaek NE (1983) Gonadal function in men with testis cancer. Fertil Steril 399:68–75
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
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
Drasga RE, Einhorn LH, Williams SD, Patel DN, Stevens EE (1983) Fertility after chemotherapy for testicular cancer. J Clin Oncol 1:179–183
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
Ettinger B, Genant HK, Cann CE (1985) Long-term estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 102:316–324
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
Fossa SD, Ons S, Abyholm T, Norman N, Leob M (1985) Post-treatment fertility in patients with testicular cancer. Cancer 57:210–214
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
Heinemann C (1982) Morphometrische, histologische und enzym-histologische Untersuchungen am Hoden der Ratte nach Gabe von Ifosfamid. Inauguraldissertation, Bonn
Heymer B (1981) Hodenbiopsie zur Diagnostik von Fertilitätsstörungen. Münch med Wochenschr 123:481–844
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
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
Kretser de DM, Burger GH, Bremner WJ (1983) Control of FSH and LH secretion. Monogr Endocrinol 25:12–43
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
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
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
Kreuser ED (1987) Inzidenz und Prognose reproduktiver und endokriner Funktionsstörungen nach kurativer zytostatischer Chemotherapie bei Patienten mit malignen Erkrankungen. Habilitationsschrift, Universität Ulm
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
Kuber W, Lunglmayr G, Seitz W, Grauthoff H, Weißbach L (1980) Fertilität bei Patienten mit Seminom des Hodens. Urologie A 19:272–275
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
Lange PH, Narayan P, Fraley EE (1984) Fertility issues following therapy for testicular cancer. Semin Urol 4:264–274
Lauritzen C (1982) Das Klimakterium der Frau. Schering, Paris Frankfurt Berlin
Leitner SP, Bosl GJ, Bajorunas D (1986) Gonadal dysfunction in patients treated for metastatic germ cell tumors. J Clin Oncol 4:1500–1505
Lienert EA (1973) Verteilungsfreie Methoden in der Biostatistik, Teil I. Anton Hain, Königstein Meisenheim, S 200–203
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
Rister M, Müller AM, Gladtke E (1983) Kinder ehemaliger krebskranker Patienten. Dtsch Med Wochenschr 108:1137–1142
Schütte B (1984A) Hodenbiopsie bei Subfertilität. In: Schirren C, Holstein AF (Hrsg) Fortschritte der Andrologie 9. Grosse, Berlin, S 166–167
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
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
Weißbach L, Lange CE, Rodermund OE, Zwicker H, Gropp A, Pothmann W (1974) Fertilitätsstörungen bei behandelten Hodentumorpatienten. Urologe A 13:80–85
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
Weißbach L, Sommerhoff Ch, Struth B (1980) Aussagen zur Fertilität bei Patienten mit germinalen Hodentumoren. Extracta urologica 3:159–174
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
World Health Organization (1979) Handbook for reporting results of cancer treatment. WHO offset publication, No 48, Geneva
Author information
Authors and Affiliations
Additional information
Die Untersuchungen wurden durch die Deutsche Krebshilfe unterstützt (M 16/86 He 3)
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01711264