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Review
. 2022 Nov;18(2):122-132.
doi: 10.17925/EE.2022.18.2.122. Epub 2022 Nov 29.

Review of the Function of the Hypothalamic-Pituitary-Gonadal Axis in Children and Adolescents with Cancer

Affiliations
Review

Review of the Function of the Hypothalamic-Pituitary-Gonadal Axis in Children and Adolescents with Cancer

Jimena Lopez Dacal et al. touchREV Endocrinol. 2022 Nov.

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.

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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

Figure 1:
Figure 1:. Risk stratification for patients with acute lymphoblastic leukaemia (ALL) according to the criteria set by the ALL IC-BFM 2002 trial,
Figure 2:
Figure 2:. Mean bilateral testicular volume in 61 boys with acute lymphoblastic or myeloid leukaemia, or non-Hodgkin lymphoma, grouped according to age or pubertal Tanner stage at the moment of clinical assessment of testicular volume no earlier than 1 year after the end of chemotherapy
Figure 3:
Figure 3:. Longitudinal follow-up of serum levels of anti-Müllerian hormone, testosterone and gonadotropins in 97 boys with acute lymphoblastic or myeloid leukaemia, or non-Hodgkin lymphoma

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