Skip to main content

Advertisement

SpringerLink
Log in

What is the damage? Testicular germ cell tumour survivors deficient in testosterone at risk of metabolic syndrome and a need for medical intervention

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Testicular germ cell tumours (TGCT) survivors are coping with late treatment sequelae. Testosterone deficiency may contribute to earlier onset of metabolic syndrome. The study aimed to assess connections between serum testosterone concentrations and metabolic disorders as well as body composition in TGCT survivors. 336 TGCT patients with over two years of complete post-treatment remission were divided into three groups: definite testosterone deficiency (< 8 nmol/L), ‘grey zone’ (8–12 nmol/L) and normal testosterone (> 12 nmol/L; control group) to assess differences in metabolism. Univariate and multivariate analyses were performed. The multivariate analysis assessed the risk of metabolic disorders and changes in body composition with regard to testosterone concentrations adjusted for age, smoking history, clinical stage, type of treatment and follow-up period. 14% of patients presented with definite testosterone deficiency; 46% were in the ‘grey zone’. On multivariate analysis, low testosterone levels were related to hyperglycemia, hypercholesterolemia, hypertriglyceridemia, inflammatory processes, procoagulant state and obesity. The odds ratio (OR) for the onset of metabolic syndrome was 2.87 (95% CI 1.74–4.73, p < 0.001) for the ‘grey zone’ patients and 7.92 (95% CI 3.76–16.70, p < 0.001) for those with definite testosterone deficiency. Testosterone concentrations were independently associated with metabolic disorders in TGCT survivors. Testicular cancer survivors often have lower testosterone and metabolic disorders. Apart from recurrence, follow-up should focus on promoting a healthy lifestyle, preventing and managing late effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Einhorn EH. Testicular cancer: an oncological success story. Clin Cancer Res. 1997;3(12 Pt 2):2630–2.

    CAS  PubMed  Google Scholar 

  2. Wiechno PJ, Kowalska M, Kucharz J, Sadowska M, Michalski W, Poniatowska G, Jońska-Gmyrek J, Rzymkowska J, Nietupski K, Demkow T. Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor. Med Oncol. 2017;34(5):84.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Berger CC, Bokemeyer C, Schuppert F, Schmoll HJ. Endocrinological late effects after chemotherapy for testicular cancer. Br J Cancer. 1996;73(9):1108–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Eberhard J, Stahl O, Cwikiel M, Cavallin-Stahl E, Giwercman Y, Salmonson EC, Giwercman A. Risk factors for post-treatment hypogonadism in testicular cancer patients. Eur J Endocrinol. 2008;158(4):561–70.

    Article  CAS  PubMed  Google Scholar 

  5. Nord C, Bjoro T, Ellingsen D, Mykletun A, Dahl O, Klepp O, Bremnes RM, Wist E, Fossa SD. Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol. 2003;44(3):322–8.

    Article  PubMed  Google Scholar 

  6. Nuver J, Smit AJ, Wolffenbuttel BH, Sluiter WJ, Hoekstra HJ, Sleijfer DT, Gietema JA. The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol. 2005;23(16):3718–25.

    Article  CAS  PubMed  Google Scholar 

  7. Puhse G, Secker A, Kemper S, Hertle L, Kliesch S. Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment. Int J Androl. 2011;34(5 Pt 2):351–7.

    Article  Google Scholar 

  8. Sprauten M, Brydoy M, Haugnes HS, Cvancarova M, Bjoro T, Bjerner J, Fossa SD, Oldenburg J. Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol. 2014;32(6):571–8.

    Article  CAS  PubMed  Google Scholar 

  9. Boer H, Proost JH, Nuver J, Bunskoek S, Gietema JQ, Geubels BM, Altena R, Zwart N, Oosting SF, Vonk JM, Lefrandt JD, Uges DR, Meijer C, de Vries EG, Gietema JA. Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors. Ann Oncol. 2015;26(11):2305–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Isaksson S, Bogefors K, Stahl O, Eberhard J, Giwercman YL, Leijonhufvud I, Link K, Ora I, Romerius P, Bobjer J, Giwercman A. High risk of hypogonadism in young male cancer survivors. Clin Endocrinol. 2018;88(3):432–41.

    Article  CAS  Google Scholar 

  11. de Haas EC, Altena R, Boezen HM, Zwart N, Smit AJ, Bakker SJ, van Roon AM, Postma A, Wolffenbuttel BH, Hoekstra HJ, van Leeuwen FE, Sleijfer DT, Gietema JA. Early development of the metabolic syndrome after chemotherapy for testicular cancer. Ann Oncol. 2013;24(3):749–55.

    Article  PubMed  Google Scholar 

  12. Haugnes HS, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, Svartberg J, Wilsgaard T, Bremnes RM. Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol. 2007;18(2):241–8.

    Article  CAS  PubMed  Google Scholar 

  13. Bogefors C, Isaksson S, Bobjer J, Kitlinski M, Leijonhufvud I, Link K, Giwercman A. Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome. Andrology. 2017;5(4):711–7.

    Article  CAS  PubMed  Google Scholar 

  14. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC, International Society of Andrology; International Society for the Study of Aging Male; European Association of Urology; European Academy of Andrology; American Society of Andrology. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol. 2009;55(1):121–30.

    Article  PubMed  Google Scholar 

  15. Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S. EAU non-oncology guidelines. Male Hypogonadism; 2018. Access Oct 2018

  16. Sieradzki J (2012) Cukrzyca i zespół metaboliczny. Interna Szczeklika Podręcznik Chorób Wewnętrznych. Med Prakt 1316–61

  17. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.

    Article  CAS  PubMed  Google Scholar 

  18. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26(6):833–76.

    Article  CAS  PubMed  Google Scholar 

  19. Skakkebaek NE, Holm M, Hoei-Hansen C, Jorgensen N, Rajpert-De ME. Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult patients with signs of maldevelopment of the testis. APMIS. 2003;111(1):1–9 (discussion 9-11).

    Article  PubMed  Google Scholar 

  20. Wiechno P, Demkow T, Kubiak K, Sadowska M, Kamińska J. The quality of life and hormonal disturbances in testicular cancer survivors in Cisplatin era. Eur Urol. 2007;52(5):1448–544.

    Article  PubMed  Google Scholar 

  21. Sprauten M, Darrah TH, Peterson DR, Campbell ME, Hannigan RE, Cvancarova M, Beard C, Haugnes HS, Fossa SD, Oldenburg J, Travis LB. Impact of long-term serum platinum concentrations on neuro- and ototoxicity in Cisplatin-treated survivors of testicular cancer. J Clin Oncol. 2012;30(3):300–7.

    Article  CAS  PubMed  Google Scholar 

  22. Wiechno P. Dynamika zaburzeń hormonalnych po orchidektomii jednostronnej z powodu nowotworu jądra. Warsaw 2013. Centrum Onkologii-Instytut [ISBN: 978-83-88681-02-8]

  23. Fossa SD, Gilbert E, Dores GM, Chen J, McGlynn KA, Schonfeld S, Storm H, Hall P, Holowaty E, Andersen A, Joensuu H, Andersson M, Kaijser M, Gospodarowicz M, Cohen R, Pukkala E, Travis LB. Noncancer causes of death in survivors of testicular cancer. J Natl Cancer Inst. 2007;99(7):533–44.

    Article  PubMed  Google Scholar 

  24. Willemse PM, van der Meer RW, Burggraaf J, van Elderen SG, de Kam ML, de Roos A, Lamb HJ, Osanto S. Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy. Acta Oncol. 2014;53(3):351–60.

    Article  CAS  PubMed  Google Scholar 

  25. Bandak M, Jorgensen N, Juul A, Lauritsen J, Oturai PS, Mortensen J, Hojman P, Helge JW, Daugaard G. Leydig cell dysfunction, systemic inflammation and metabolic syndrome in long-term testicular cancer survivors. Eur J Cancer. 2017;84:9–17.

    Article  CAS  PubMed  Google Scholar 

  26. Morote J, Morin JP, Orsola A, Abascal JM, Salvador C, Trilla E, Raventos CX, Cecchini L, Encabo G, Reventos J. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology. 2007;69(3):500–4.

    Article  PubMed  Google Scholar 

  27. Willemse PM, Hamdy NA, van Wulften L, van Steijn-van Tol AQ, Putter H, Osanto S. Prevalence of vertebral fractures independent of BMD and anticancer treatment in patients with testicular germ cell tumors. J Clin Endocrinol Metab. 2010;95(11):4933–42.

    Article  CAS  PubMed  Google Scholar 

  28. Haugnes HS, Wethal T, Aass N, Dahl O, Klepp O, Langberg CW, Wilsgaard T, Bremnes RM, Fossa SD. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol. 2010;28(30):4649–57.

    Article  PubMed  Google Scholar 

  29. Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MP, Nicolai N, Oldenburg J. EAU Oncology guidelines. Testicular Cancer 2018. Dostęp on-line. Accessed Feb 2018

Download references

Author information

Authors and Affiliations

  1. Department of Uro-Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 5 Roentgena st., 02-781, Warsaw, Poland

    Grazyna Poniatowska, Wojciech Michalski, Jakub Kucharz, Joanna Jonska-Gmyrek, Karol Nietupski, Tomasz Demkow, Malgorzata Sadowska, Tomasz Kalinowski, Beata Grochulska-Nalazek, Ada Nowatorska, Pawel Stelmasiak & Pawel J. Wiechno

  2. Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland

    Paulina Wieszczy

  3. Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

    Paulina Wieszczy

  4. Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

    Marek Dedecjus

Authors
  1. Grazyna Poniatowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wojciech Michalski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jakub Kucharz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joanna Jonska-Gmyrek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paulina Wieszczy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Karol Nietupski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomasz Demkow
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marek Dedecjus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Malgorzata Sadowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tomasz Kalinowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Beata Grochulska-Nalazek
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ada Nowatorska
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pawel Stelmasiak
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Pawel J. Wiechno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jakub Kucharz.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Poniatowska, G., Michalski, W., Kucharz, J. et al. What is the damage? Testicular germ cell tumour survivors deficient in testosterone at risk of metabolic syndrome and a need for medical intervention. Med Oncol 37, 82 (2020). https://doi.org/10.1007/s12032-020-01407-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-020-01407-4

Keywords

Search

Navigation