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Fertility preservation for people with cancer

Pubertal development

Clinical Question

Are children who receive cancer treatment at increased risk of pubertal arrest or delay after treatment?

Surprisingly few studies have investigated the impact that cancer treatment may have on the pubertal development of people with a history of cancer during childhood, considering the potential impact of cancer treatment on fertility. Most are from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study of children and adolescents treated for childhood cancer at 26 collaborating institutions in the United States and Canada. Prospective studies are needed to enhance the data discussed in this section.

Delayed puberty

Data from the CCSS identified children with a history of brain tumors and rhabdomyosarcoma to be at increased risk of late-onset hypothyroidism, growth hormone deficiency and the need for medications to induce puberty.[1][2] Delayed puberty and growth hormone deficiency was also more likely in a smaller cohort of Japanese children with a history of cancer.[3]

Timing of menarche

Data from the CCSS of children with a history of acute lymphoblastic leukaemia (ALL), confirm results from an earlier, smaller study[4] that identified the timing of menarche for girls to be in the normal range.[5] These studies suggest that abnormal timing of menarche is more likely to occur in ALL patients who receive cranial or craniospinal radiotherapy.[4][5] A separate study from the CCSS identified children with a history of central nervous system tumours may be more likely to have early onset of menarche.[6]

Evidence Summary

Evidence summaryLevelReferences
Children who receive cancer treatment are at risk of developing late-onset hypothyroidism, growth hormone deficiency, a need for medications to induce puberty and abnormal timing of menarche.II, III-3[1], [2], [3], [4], [5], [6]

Recommendation

Evidence-based recommendationGrade
Health professionals should be aware of the potential impact of cancer treatment on the pubertal development of children diagnosed with cancer. It is important that children with a history of cancer receive appropriate follow-up care, with paediatric endocrinology and gynaecology/andrology to monitor pubertal development and treat pubertal delay.C

References

  1. Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 2003 Feb 1;97(3):663-73 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12548609.
  2. Punyko JA, Mertens AC, Gurney JG, Yasui Y, Donaldson SS, Rodeberg DA, et al. Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study. Pediatr Blood Cancer 2005 Jun 15;44(7):643-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15700252.
  3.  Ozono S, Ishida Y, Honda M, Okamura J, Asami K, Maeda N, et al. General health status and late effects among adolescent and young adult survivors of childhood cancer in Japan. Jpn J Clin Oncol 2014 Oct;44(10):932-40 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25108030.
  4. Mills JL, Fears TR, Robison LL, Nicholson HS, Sklar CA, Byrne J. Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. J Pediatr 1997 Oct;131(4):598-602 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9386666.
  5. Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, et al. Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2008 Apr;50(4):854-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17729247.
  6. Armstrong GT, Whitton JA, Gajjar A, Kun LE, Chow EJ, Stovall M, et al. Abnormal timing of menarche in survivors of central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer 2009 Jun 1;115(11):2562-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19309737.

Body of evidence

Are children who received cancer treatment, compared to children in the general population, at increased risk of pubertal arrest or delay after treatment?

CitationLevel of EvidenceQuality of EvidenceSize of EffectNumber of PatientsRelevance of Evidence
Armstrong GT, Whitton JA, Gajjar A, Kun LE, Chow EJ, Stovall M, et al. Abnormal timing of menarche in survivors of central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer 2009 Jun 1;115(11):2562-70 Available from:http://www.ncbi.nlm.nih.gov/pubmed/19309737 III-3MediumN/A1,235N/A
Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, et al. Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2008 Apr;50(4):854-8 Available from:http://www.ncbi.nlm.nih.gov/pubmed/17729247 IIMediumN/A2,077N/A
Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, et al. Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 2003 Feb 1;97(3):663-73 Available from:http://www.ncbi.nlm.nih.gov/pubmed/12548609 IILowN/A5,025N/A
Mills JL, Fears TR, Robison LL, Nicholson HS, Sklar CA, Byrne J. Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. J Pediatr 1997 Oct;131(4):598-602 Available from:http://www.ncbi.nlm.nih.gov/pubmed/9386666 III-3MediumN/A406N/A
Ozono S, Ishida Y, Honda M, Okamura J, Asami K, Maeda N, et al. General health status and late effects among adolescent and young adult survivors of childhood cancer in Japan. Jpn J Clin Oncol 2014 Oct;44(10):932-40 Available from:http://www.ncbi.nlm.nih.gov/pubmed/25108030 III-3MediumN/A1,257N/A
Punyko JA, Mertens AC, Gurney JG, Yasui Y, Donaldson SS, Rodeberg DA, et al. Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study. Pediatr Blood Cancer 2005 Jun 15;44(7):643-53 Available from:http://www.ncbi.nlm.nih.gov/pubmed/15700252  III-3MediumN/A4,307N/A
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Cancer Council Australia