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

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

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.

Publication types

  • Review

Grants and funding

Support: This work was partially funded by grants PID-C #2017-0032 and PICT #2018-02972 of FONCYT (Fondo para la Investigacièn Científica y Tecnolègica), Argentina. Jimena Lopez Dacal is the recipient of a doctoral fellowship from FONCYT, Argentina. These funding sources had no role in the preparation of the manuscript.