Skip to main content
Log in

Dynamics of fertility impairment in childhood brain tumour survivors

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Fertility impairment and recovery after chemo- and radiotherapy have been reported in both male and female childhood cancer survivors, but little is known about the dynamics. Our aim, therefore, was to describe the development of fertility impairment and possible recovery in childhood brain tumour survivors.

Methods

In this longitudinal study, we included 144 survivors, who were treated in two German paediatric oncology centres between 2000 and 2005. Fertility parameters were retrieved from medical records up to 12 years after diagnosis.

Results

Participants with age ≥13 years and formerly cranial irradiation ≥30 Gray (n = 23), including 83 % (n = 19) with craniospinal irradiation ≥30 Gray, had a higher median FSH concentration compared to 29 patients without chemoradiotherapy: 8.3 IU/l (IQR 6.5–11.2) versus 4.1 IU/l (IQR 3.2–5.1) 2 years after initial treatment; 8.9 IU/l (IQR 8.5–10.8) versus 4.2 IU/l (IQR 2.4–6.7) after 8 years; and 7.1 IU/l (IQR 6.7–7.7) versus 3.5 IU/l (IQR 2.8–4.2) after 10 years. Altogether, 11/65 women reported the occurrence of amenorrhoea 6.0 years (range 1–10) after diagnosis. Five of these women later developed a regular menstrual cycle without hormone replacement therapy. Patients’ chance of recovery from fertility impairment was increased with time since diagnosis (p = 0.074).

Conclusion

Signs of fertility impairment such as amenorrhoea and elevated FSH levels were observed at variable time points between 1 and 12 years after chemoradiotherapy. Decreasing FSH levels were observed 1–7 years after elevation and were interpreted either as an atrophy of the pituitary gland or as recovery from fertility impairment.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Andersson AM, Skakkebaek NE (2001) Serum inhibin B levels during male childhood and puberty. Mol Cell Endocrinol 180(1–2):103–107

    Article  PubMed  CAS  Google Scholar 

  • Armstrong GT, Liu Q, Yasui Y, Huang S, Ness KK, Leisenring W, Hudson MM, Donaldson SS, King AA, Stovall M, Krull KR, Robison LL, Packer RJ (2009) Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst 101(13):946–958. doi:10.1093/jnci/djp148

    Article  PubMed  PubMed Central  Google Scholar 

  • Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, Sklar CA, Robison LL, Diller L (2013) Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 14(9):873–881. doi:10.1016/S1470-2045(13)70251-1

    Article  PubMed  Google Scholar 

  • CBTRUS (2008) Statistical report: primary brain tumors in the United States, 2000–2004. Published by the Central Brain Tumor Registry of the United States

  • Constine LS, Woolf PD, Cann D, Mick G, McCormick K, Raubertas RF, Rubin P (1993) Hypothalamic–pituitary dysfunction after radiation for brain tumors. N Engl J Med 328(2):87–94. doi:10.1056/NEJM199301143280203

    Article  PubMed  CAS  Google Scholar 

  • Dittrich R (2010) Gonadenschädigungen nach onkologischer Behandlung. Fertilitätserhalt für Kinder und Jugendliche. Journal der Arbeitsgemeinschaft Kinder- und Jugendgynäkologie Korasion 25:23–26

    Google Scholar 

  • Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, Donaldson SS, Byrne J, Robison LL (2009a) Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 27(16):2677–2685. doi:10.1200/JCO.2008.20.1541

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, Yasui Y (2009b) Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 27(14):2374–2381. doi:10.1200/JCO.2008.21.1839

    Article  PubMed  PubMed Central  Google Scholar 

  • Illing S, Classen M (2005) Klinikleitfaden Pädiatrie. Urban und Fischer Verlag 5. Auflage S797

  • Koustenis E, Pfitzer C, Balcerek M, Reinmuth S, Zynda A, Stromberger C, Hohmann C, Keil T, Borgmann-Staudt A (2013) Impact of cranial irradiation and brain tumor location on fertility: a survey. Klin Padiatr 225(6):320–324. doi:10.1055/s-0033-1353206

    Article  PubMed  CAS  Google Scholar 

  • Lai SF, Wang CW, Chen YH, Lan KH, Cheng JC, Cheng AL, Kuo SH (2012) Medulloblastoma in adults. Treatment outcome, relapse patterns, and prognostic factors. Strahlenther Onkol 188(10):878–886. doi:10.1007/s00066-012-0168-2

    Article  PubMed  Google Scholar 

  • Littley MD, Shalet SM, Beardwell CG, Robinson EL, Sutton ML (1989) Radiation-induced hypopituitarism is dose-dependent. Clin Endocrinol 31(3):363–373

    Article  CAS  Google Scholar 

  • Meirow D, Biederman H, Anderson RA, Wallace WH (2010) Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol 53(4):727–739. doi:10.1097/GRF.0b013e3181f96b54

    Article  PubMed  Google Scholar 

  • Mertens AC, Ramsay NK, Kouris S, Neglia JP (1998) Patterns of gonadal dysfunction following bone marrow transplantation. Bone Marrow Transplant 22(4):345–350. doi:10.1038/sj.bmt.1701342

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JD, Hitchen C, Vlachaki MT (2007) Role of ovarian transposition based on the dosimetric effects of craniospinal irradiation on the ovaries: a case report. Med Dosim 32(3):204–210. doi:10.1016/j.meddos.2007.02.004

    Article  PubMed  Google Scholar 

  • Mulhall JP (2011) Cancer and sexual health. Springer, Berlin, pp 207–208

    Book  Google Scholar 

  • Muller K, Gnekow A, Falkenstein F, Scheiderbauer J, Zwiener I, Pietsch T, Warmuth-Metz M, Voges J, Nikkhah G, Flentje M, Combs SE, Vordermark D, Kocher M, Kortmann RD (2013) Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH). Strahlenther Onkol 189(8):647–655. doi:10.1007/s00066-013-0357-7

    Article  PubMed  CAS  Google Scholar 

  • Nishi Y, Hamamoto K, Fujita N, Okada S (2011) Empty sella/pituitary atrophy and endocrine impairments as a consequence of radiation and chemotherapy in long-term survivors of childhood leukemia. Int J Hematol 94(4):399–402. doi:10.1007/s12185-011-0939-z

    Article  PubMed  CAS  Google Scholar 

  • Pagon RA, Adam MP, Bird TD (1993–2013) Isolated gonadotropin-releasing hormone (GnRH) deficiency. GeneReviews. University of Washington, Seattle

  • Reinmuth S, Liebeskind AK, Wickmann L, Bockelbrink A, Keil T, Henze G, Borgmann A (2008) Having children after surviving cancer in childhood or adolescence—results of a Berlin survey. Klin Padiatr 220(3):159–165. doi:10.1055/s-2008-1073143

    Article  PubMed  CAS  Google Scholar 

  • Robinson KE, Kuttesch JF, Champion JE, Andreotti CF, Hipp DW, Bettis A, Barnwell A, Compas BE (2010) A quantitative meta-analysis of neurocognitive sequelae in survivors of pediatric brain tumors. Pediatr Blood Cancer 55(3):525–531. doi:10.1002/pbc.22568

    Article  PubMed  Google Scholar 

  • Romerius P, Stahl O, Moell C, Relander T, Cavallin-Stahl E, Wiebe T, Giwercman YL, Giwercman A (2009) Hypogonadism risk in men treated for childhood cancer. J Clin Endocrinol Metab 94(11):4180–4186. doi:10.1210/jc.2009-0337

    Article  PubMed  CAS  Google Scholar 

  • Sklar CA (2002) Childhood brain tumors. J Pediatr Endocrinol Metab 15(Suppl 2):669–673

    PubMed  Google Scholar 

  • Strenger V, Lackner H, Mayer R, Sminia P, Sovinz P, Mokry M, Pilhatsch A, Benesch M, Schwinger W, Seidel M, Sperl D, Schmidt S, Urban C (2013) Incidence and clinical course of radionecrosis in children with brain tumors. A 20-year longitudinal observational study. Strahlenther Onkol 189(9):759–764. doi:10.1007/s00066-013-0408-0

    Article  PubMed  CAS  Google Scholar 

  • Takano K, Utsunomiya H, Ono H, Ohfu M, Okazaki M (1999) Normal development of the pituitary gland: assessment with three-dimensional MR volumetry. AJNR Am J Neuroradiol 20(2):312–315

    PubMed  CAS  Google Scholar 

  • van Dorp W, van der Geest IM, Laven JS, Hop WC, Neggers SJ, de Vries AC, Pieters R, van den Heuvel-Eibrink MM (2013) Gonadal function recovery in very long-term male survivors of childhood cancer. Eur J Cancer 49(6):1280–1286. doi:10.1016/j.ejca.2012.12.007

    Article  PubMed  Google Scholar 

  • von Wolff M (2014) FertiPROTEKT. http://www.fertiprotekt.de/index.php?PHPSESSID=jg022gjofr0udvq7hf0fdgvnr5&lang=de&id=641. Accessed 03.04.14

  • Wallace WH (2011) Oncofertility and preservation of reproductive capacity in children and young adults. Cancer 117(10 Suppl):2301–2310. doi:10.1002/cncr.26045

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This longitudinal study was supported by the Berliner Krebsgesellschaft e.V., the Kind Philipp Foundation for Leukaemia Research (Kind-Philipp-Stiftung für Leukämieforschung) in the Association of Sponsors for the Promotion of German Science (Stifterverband für die Deutsche Wissenschaft) and by the Charité University Medical Center Berlin. We are grateful to Dr. Birgit Spors for analysing the MRI scans.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Borgmann-Staudt.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pfitzer, C., Chen, CM., Wessel, T. et al. Dynamics of fertility impairment in childhood brain tumour survivors. J Cancer Res Clin Oncol 140, 1759–1767 (2014). https://doi.org/10.1007/s00432-014-1702-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1702-7

Keywords

Navigation