Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 May;73(9):1108–1114. doi: 10.1038/bjc.1996.213

Endocrinological late effects after chemotherapy for testicular cancer.

C C Berger 1, C Bokemeyer 1, F Schuppert 1, H J Schmoll 1
PMCID: PMC2074412  PMID: 8624272

Abstract

Type and extent of endocrinological alterations were studied in long-term disease-free survivors after cisplatin-based chemotherapy for testicular cancer. A total of 63 patients with a median age of 30 (19-53) years, and median follow-up of 42 (16-128) months were included. Elevated serum follicle-stimulating hormone (FSH) levels were found in 63% of patients, 24% showed pathologically elevated luteinising hormone (LH) levels with normal and 10% with subnormal testosterone levels. The degree of gonadotropin elevation was highly significantly correlated with the cumulative platinum (P) dose. Patients treated with platinum-vinblastine-bleomycin regimens showed higher gonadotropin levels than those treated with platinum-etoposide-bleomycin. The adrenal androgen dehydroepiandrosterone (DHEA), pathologically elevated in 68% of patients, was significantly correlated with the cumulative doses of chemotherapy (ctx) used and to the gonadotropin levels. Treatment variables, such as type and dose of cytotoxic agents used, as well as degree of gonadotropin elevation were further correlated with changes in oestron, testosterone and 17 alpha-OH-progesterone levels. Cholesterol levels were elevated in 32% of patients and significant interactions between the steroid hormone levels and cardiovascular risk factors could be shown.

Full text

PDF
1108

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aass N., Kaasa S., Lund E., Kaalhus O., Heier M. S., Fosså S. D. Long-term somatic side-effects and morbidity in testicular cancer patients. Br J Cancer. 1990 Jan;61(1):151–155. doi: 10.1038/bjc.1990.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aksoy I. A., Sochorová V., Weinshilboum R. M. Human liver dehydroepiandrosterone sulfotransferase: nature and extent of individual variation. Clin Pharmacol Ther. 1993 Nov;54(5):498–506. doi: 10.1038/clpt.1993.181. [DOI] [PubMed] [Google Scholar]
  3. Bain J., Langevin R., D'Costa M., Sanders R. M., Hucker S. Serum pituitary and steroid hormone levels in the adult male: one value is as good as the mean of three. Fertil Steril. 1988 Jan;49(1):123–126. doi: 10.1016/s0015-0282(16)59662-9. [DOI] [PubMed] [Google Scholar]
  4. Barrett-Connor E., Khaw K. T. Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation. 1988 Sep;78(3):539–545. doi: 10.1161/01.cir.78.3.539. [DOI] [PubMed] [Google Scholar]
  5. Barrett-Connor E., Khaw K. T., Yen S. S. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986 Dec 11;315(24):1519–1524. doi: 10.1056/NEJM198612113152405. [DOI] [PubMed] [Google Scholar]
  6. Berger C. C., Bokemeyer C., Schneider M., Kuczyk M. A., Schmoll H. J. Secondary Raynaud's phenomenon and other late vascular complications following chemotherapy for testicular cancer. Eur J Cancer. 1995 Dec;31A(13-14):2229–2238. doi: 10.1016/0959-8049(95)00460-2. [DOI] [PubMed] [Google Scholar]
  7. Bissett D., Kunkeler L., Zwanenburg L., Paul J., Gray C., Swan I. R., Kerr D. J., Kaye S. B. Long-term sequelae of treatment for testicular germ cell tumours. Br J Cancer. 1990 Oct;62(4):655–659. doi: 10.1038/bjc.1990.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blackman M. R., Weintraub B. D., Rosen S. W., Harman S. M. Comparison of the effects of lung cancer, benign lung disease, and normal aging on pituitary-gonadal function in men. J Clin Endocrinol Metab. 1988 Jan;66(1):88–95. doi: 10.1210/jcem-66-1-88. [DOI] [PubMed] [Google Scholar]
  9. Bokemeyer C., Schmoll H. J., van Rhee J., Kuczyk M., Schuppert F., Poliwoda H. Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma. Ann Hematol. 1994 Mar;68(3):105–110. doi: 10.1007/BF01727413. [DOI] [PubMed] [Google Scholar]
  10. Bosl G. J., Bajorunas D. Pituitary and testicular hormonal function after treatment for germ cell tumours. Int J Androl. 1987 Feb;10(1):381–384. doi: 10.1111/j.1365-2605.1987.tb00206.x. [DOI] [PubMed] [Google Scholar]
  11. Boyer M., Raghavan D., Harris P. J., Lietch J., Bleasel A., Walsh J. C., Anderson S., Tsang C. S. Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer. J Clin Oncol. 1990 Jan;8(1):21–26. doi: 10.1200/JCO.1990.8.1.21. [DOI] [PubMed] [Google Scholar]
  12. Campos J. L. Continuous positive ageing in Hodgkin's disease. Br J Radiol. 1972 Dec;45(540):917–922. doi: 10.1259/0007-1285-45-540-917. [DOI] [PubMed] [Google Scholar]
  13. Carroll P. R., Whitmore W. F., Jr, Herr H. W., Morse M. J., Sogani P. C., Bajorunas D., Fair W. R., Chaganti R. S. Endocrine and exocrine profiles of men with testicular tumors before orchiectomy. J Urol. 1987 Mar;137(3):420–423. doi: 10.1016/s0022-5347(17)44054-7. [DOI] [PubMed] [Google Scholar]
  14. Cochran J. S., Walsh P. C., Porter J. C., Nicholson T. C., Madden J. D., Peters P. C. The endocrinology of human chorionic gonadotropin-secreting testicular tumors: new methods in diagnosis. J Urol. 1975 Oct;114(4):549–555. doi: 10.1016/s0022-5347(17)67080-0. [DOI] [PubMed] [Google Scholar]
  15. Drasga R. E., Einhorn L. H., Williams S. D., Patel D. N., Stevens E. E. Fertility after chemotherapy for testicular cancer. J Clin Oncol. 1983 Mar;1(3):179–183. doi: 10.1200/JCO.1983.1.3.179. [DOI] [PubMed] [Google Scholar]
  16. Einhorn L. H., Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977 Sep;87(3):293–298. doi: 10.7326/0003-4819-87-3-293. [DOI] [PubMed] [Google Scholar]
  17. Ellis P. A., Fitzharris B. M., George P. M., Robinson B. A., Atkinson C. H., Colls B. M. Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol. 1992 Oct;10(10):1609–1614. doi: 10.1200/JCO.1992.10.10.1609. [DOI] [PubMed] [Google Scholar]
  18. Fosså S. D., Ous S., Abyholm T., Norman N., Loeb M. Post-treatment fertility in patients with testicular cancer. II. Influence of cis-platin-based combination chemotherapy and of retroperitoneal surgery on hormone and sperm cell production. Br J Urol. 1985 Apr;57(2):210–214. doi: 10.1111/j.1464-410x.1985.tb06426.x. [DOI] [PubMed] [Google Scholar]
  19. Gietema J. A., Sleijfer D. T., Willemse P. H., Schraffordt Koops H., van Ittersum E., Verschuren W. M., Kromhout D., Sluiter W. J., Mulder N. H., de Vries E. G. Long-term follow-up of cardiovascular risk factors in patients given chemotherapy for disseminated nonseminomatous testicular cancer. Ann Intern Med. 1992 May 1;116(9):709–715. doi: 10.7326/0003-4819-116-9-709. [DOI] [PubMed] [Google Scholar]
  20. Giona F., Annino L., Donato P., Ermini M. Gonadal, adrenal, androgen and thyroid functions in adults treated for acute lymphoblastic leukemia. Haematologica. 1994 Mar-Apr;79(2):141–147. [PubMed] [Google Scholar]
  21. Haffner S. M., Mykkänen L., Valdez R. A., Katz M. S. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993 Dec;77(6):1610–1615. doi: 10.1210/jcem.77.6.8263149. [DOI] [PubMed] [Google Scholar]
  22. Hansen S. W., Berthelsen J. G., 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 Oncol. 1990 Oct;8(10):1695–1698. doi: 10.1200/JCO.1990.8.10.1695. [DOI] [PubMed] [Google Scholar]
  23. Hendry W. F., Stedronska J., Jones C. R., Blackmore C. A., Barrett A., Peckham M. J. Semen analysis in testicular cancer and Hodgkin's disease: pre- and post-treatment findings and implications for cryopreservation. Br J Urol. 1983 Dec;55(6):769–773. doi: 10.1111/j.1464-410x.1983.tb03423.x. [DOI] [PubMed] [Google Scholar]
  24. Holmes S. J., Whitehouse R. W., Clark S. T., Crowther D. C., Adams J. E., Shalet S. M. Reduced bone mineral density in men following chemotherapy for Hodgkin's disease. Br J Cancer. 1994 Aug;70(2):371–375. doi: 10.1038/bjc.1994.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Höppner W., Reinel D., Hartmann M. Untersuchungen zur Fertilität von Patienten mit malignen Hodentumoren zum Zeitpunkt der Orchidektomie. Beitrag zur Frage nach dem Sinn der Kryokonservierung. Andrologia. 1986 Jul-Aug;18(4):398–405. [PubMed] [Google Scholar]
  26. Jacobs D. R., Jr, Mebane I. L., Bangdiwala S. I., Criqui M. H., Tyroler H. A. High density lipoprotein cholesterol as a predictor of cardiovascular disease mortality in men and women: the follow-up study of the Lipid Research Clinics Prevalence Study. Am J Epidemiol. 1990 Jan;131(1):32–47. doi: 10.1093/oxfordjournals.aje.a115483. [DOI] [PubMed] [Google Scholar]
  27. Krause W., Pflüger K. H. Treatment with the gonadotropin-releasinghormone agonist buserelin to protect spermatogenesis against cytotoxic treatment in young men. Andrologia. 1989 May-Jun;21(3):265–270. [PubMed] [Google Scholar]
  28. Kreuser E. D., Kurrle E., Hetzel W. D., Heymer B., Porzsolt F., Hautmann R., Gaus W., Schlipf U., Pfeiffer E. F., Heimpel H. Reversible Keimzelltoxizität nach aggressiver Chemotherapie bei Patienten mit Hodentumoren: Ergebnisse einer prospektiven Studie. Klin Wochenschr. 1989 Apr 3;67(7):367–378. doi: 10.1007/BF01711264. [DOI] [PubMed] [Google Scholar]
  29. LeBlanc G. A., Kantoff P. W., Ng S. F., Frei E., 3rd, Waxman D. J. Hormonal perturbations in patients with testicular cancer treated with cisplatin. Cancer. 1992 May 1;69(9):2306–2310. doi: 10.1002/1097-0142(19920501)69:9<2306::aid-cncr2820690917>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  30. Leitner S. P., Bosl G. J., Bajorunas D. Gonadal dysfunction in patients treated for metastatic germ-cell tumors. J Clin Oncol. 1986 Oct;4(10):1500–1505. doi: 10.1200/JCO.1986.4.10.1500. [DOI] [PubMed] [Google Scholar]
  31. Liu C. H., Laughlin G. A., Fischer U. G., Yen S. S. Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: evidence for a reduced 17,20-desmolase enzymatic activity. J Clin Endocrinol Metab. 1990 Oct;71(4):900–906. doi: 10.1210/jcem-71-4-900. [DOI] [PubMed] [Google Scholar]
  32. Maines M. D., Sluss P. M., Iscan M. cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis. Endocrinology. 1990 May;126(5):2398–2406. doi: 10.1210/endo-126-5-2398. [DOI] [PubMed] [Google Scholar]
  33. Mancini R. E., Lavieri J. C., Muller F., Andrada J. A., Saraceni D. J. Effect of prednisolone upon normal and pathologic human spermatogenesis. Fertil Steril. 1966 Jul-Aug;17(4):500–513. doi: 10.1016/s0015-0282(16)36008-3. [DOI] [PubMed] [Google Scholar]
  34. Neil H. A., Mant D., Jones L., Morgan B., Mann J. I. Lipid screening: is it enough to measure total cholesterol concentration? BMJ. 1990 Sep 22;301(6752):584–587. doi: 10.1136/bmj.301.6752.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Orentreich N., Brind J. L., Rizer R. L., Vogelman J. H. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984 Sep;59(3):551–555. doi: 10.1210/jcem-59-3-551. [DOI] [PubMed] [Google Scholar]
  36. Pasquali R., Casimirri F., Cantobelli S., Melchionda N., Morselli Labate A. M., Fabbri R., Capelli M., Bortoluzzi L. Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism. 1991 Jan;40(1):101–104. doi: 10.1016/0026-0495(91)90199-7. [DOI] [PubMed] [Google Scholar]
  37. Raghavan D., Cox K., Childs A., Grygiel J., Sullivan D. Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol. 1992 Sep;10(9):1386–1389. doi: 10.1200/JCO.1992.10.9.1386. [DOI] [PubMed] [Google Scholar]
  38. Regelson W., Loria R., Kalimi M. Dehydroepiandrosterone (DHEA)--the "mother steroid". I. Immunologic action. Ann N Y Acad Sci. 1994 May 31;719:553–563. doi: 10.1111/j.1749-6632.1994.tb56859.x. [DOI] [PubMed] [Google Scholar]
  39. Roth B. J., Greist A., Kubilis P. S., Williams S. D., Einhorn L. H. Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up. J Clin Oncol. 1988 Aug;6(8):1239–1247. doi: 10.1200/JCO.1988.6.8.1239. [DOI] [PubMed] [Google Scholar]
  40. Schwabe H. R., Herrmann R., Mathew M., Gräf K. J., Sander T., Cordes M., Nagel R., Weissbach L., Huhn D. Langfristige Toxizität der Polychemotherapie bei kurativ behandeltem Hodenkarzinom. Dtsch Med Wochenschr. 1992 Jan 24;117(4):121–126. doi: 10.1055/s-2008-1062289. [DOI] [PubMed] [Google Scholar]
  41. Zumoff B., Rosenfeld R. S., Strain G. W., Levin J., Fukushima D. K. Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults. J Clin Endocrinol Metab. 1980 Aug;51(2):330–333. doi: 10.1210/jcem-51-2-330. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES