Review of the Function of the Hypothalamic-Pituitary-Gonadal Axis in Children and Adolescents with Cancer
- PMID: 36694892
- PMCID: PMC9835818
- DOI: 10.17925/EE.2022.18.2.122
Review of the Function of the Hypothalamic-Pituitary-Gonadal Axis in Children and Adolescents with Cancer
Abstract
The most common malignancies in childhood are leukaemias, brain tumours, lymphomas, neuroblastomas, soft tissue sarcomas and kidney tumours. At present, about 80% of childhood cancers can be treated successfully, which has significantly increased long-term survival. Concomitantly, adult gonadal function in childhood cancer survivors has become a concern. However, the immediate effect of cancer and its management on the reproductive axis function has received less attention. We conducted a review of the effects of malignancies and their treatments on the gonadal axis during childhood and adolescence. Some results are controversial, probably because the analyses do not distinguish between the malignancy types, their treatments and/or the age at treatment. However, there is agreement that cancer can partially affect gonadal function before treatment, as revealed by low circulating levels of inhibin B and anti-Müllerian hormone. Subsequently, chemotherapy transiently impairs the somatic component of the gonads (i.e. testicular Sertoli cells and ovarian granulosa cells) with normalization after treatment ends. The impact of chemotherapy may persist through adulthood after more intensive chemotherapy regimens, radiotherapy and conditioning for haematopoietic stem cell transplantation, when there is a severe impairment of the somatic component of the gonads or of the stem germ cells.
Keywords: Childhood; gonadal function; hypothalamic–pituitary–gonadal axis; malignancy; ovary; testis.
© Touch Medical Media 2022.
Conflict of interest statement
Disclosures: Romina P Grinspon reports lecture honoraria from Novo Nordisk and Raffo, and travel grants from Merck, Novo Nordisk, Pfizer, and Sandoz. Romina P Grinspon and Rodolfo A Rey have received honoraria from CONICET (Argentina) for technology services using the AMH ELISA until 2020. Rodolfo A Rey also received royalties derived from an agreement between INSERM (France) and Beckman-Coulter-Immunotech until 2020, for the development of an AMH ELISA kit, as well as lecture honoraria from Novo Nordisk and Sandoz, and travel grants from Biosidus, Merck, Novo Nordisk, Pfizer and Sandoz. Jimena Lopez Dacal has no financial or non-financial relationships or activities to declare in relation to this article.
Figures



Similar articles
-
Safety of standardised treatments for haematologic malignancies as regards to testicular endocrine function in children and teenagers.Hum Reprod. 2019 Dec 1;34(12):2480-2494. doi: 10.1093/humrep/dez216. Hum Reprod. 2019. PMID: 31768530
-
The impact of childhood cancer and its treatment on puberty and subsequent hypothalamic pituitary and gonadal function, in both boys and girls.Best Pract Res Clin Endocrinol Metab. 2019 Jun;33(3):101291. doi: 10.1016/j.beem.2019.101291. Epub 2019 Jul 9. Best Pract Res Clin Endocrinol Metab. 2019. PMID: 31327697 Review.
-
Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.Gynecol Endocrinol. 2005 Jul;21(1):18-26. doi: 10.1080/09513590500099255. Gynecol Endocrinol. 2005. PMID: 16048797
-
Testicular Function of Childhood Cancer Survivors: Who Is Worse?J Clin Med. 2019 Dec 13;8(12):2204. doi: 10.3390/jcm8122204. J Clin Med. 2019. PMID: 31847212 Free PMC article.
-
Impact of cancer therapy on the reproductive axis.Horm Res. 2003;59 Suppl 1:12-20. doi: 10.1159/000067835. Horm Res. 2003. PMID: 12566715 Review.
Cited by
-
Evaluation of ovarian functions in girls treated for hematological malignancy.Sci Rep. 2025 Mar 4;15(1):7542. doi: 10.1038/s41598-025-92411-z. Sci Rep. 2025. PMID: 40038512 Free PMC article.
-
Testicular dysfunction at diagnosis in children and teenagers with haematopoietic malignancies improves after initial chemotherapy.Front Endocrinol (Lausanne). 2023 May 16;14:1135467. doi: 10.3389/fendo.2023.1135467. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 37260445 Free PMC article.
References
-
- Crowne E, Gleeson H, Benghiat H. et al. Effect of cancer treatment on hypothalamic-pituitary function. Lancet Diabetes Endocrinol. 2015;3:568–76. - PubMed
-
- Jahnukainen K, Stukenborg JB. Clinical review: Present and future prospects of male fertility preservation for children and adolescents. J Clin Endocrinol Metab. 2012;97:4341–51. - PubMed
-
- Gebauer J, Higham C, Langer T. et al. Long-term endocrine and metabolic consequences of cancer treatment: A systematic review. Endocr Rev. 2019;40:711–67. - PubMed
-
- Rey RA, Tena-Sempere M.. Puberty: Recent advancements in its physiology and the management of its disorders. Curr Opin Endocr Metab Res. 2020;14:iv–vii.
Publication types
LinkOut - more resources
Full Text Sources