Testicular dysfunction at diagnosis in children and teenagers with haematopoietic malignancies improves after initial chemotherapy

Frontiers in Endocrinology

Endocrinology

Ignacio Bergadá¹  Romina P. Grinspon¹  Jimena Lopez Dacal¹  Maria Gabriela Ropelato¹  Maria Eugenia Rodriguez¹  Lourdes Correa Brito¹  Patricia Bedecarrás¹  Maria Gabriela Ballerini¹  Rodolfo A. Rey¹  Silvina Prada²  Marcela Soria²  Luis Aversa²  Marcela E. Gutiérrez²  Cristina Ferraro²  Guillermo Drelichman²  Lorena Morán² 

[1]Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

[2]Unidad de Hematología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

关键词: AMH;    inhibin B;    chemotherapy;    gonadotropins;    hypogonadism;    leukemia;    lymphoma;    testosterone;   

DOI  :  10.3389/fendo.2023.1135467

 received in 2022-12-31, accepted in 2023-04-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionHematopoietic malignancies are the most frequent type of cancer in childhood. Recent advances in cancer treatment have significantly improved survival until adulthood. There is an extensive literature on the effects of cancer treatment on the gonadal axis in adult survivors of childhood cancer mainly focused on sperm production, but scarce information exists on the immediate impact of cancer and its treatment in boys.ObjectivesIn this work, we determined the status of the hypothalamic-pituitary-testicular (HPT) axis function at diagnosis and the immediate impact of chemotherapy at the start of treatment in children and adolescents with hematopoietic malignancies.Subjects and methodsIn a prospective study of 94 boys and adolescents with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or non-Hodgkin lymphoma (NHL), we determined serum AMH, inhibin B and FSH to assess the gonadotrophin-Sertoli cell component of the HPT axis, and testosterone and LH to evaluate the gonadotrophin-Leydig cell component, at diagnosis and after 3 months of chemotherapy. Secondarily, the general health state was evaluated.ResultsIn prepubertal boys, at diagnosis, AMH, inhibin B and FSH were lower compared to the reference population, reflecting an FSH-Sertoli cell axis dysfunction. After 3 months of chemotherapy, all hormone concentrations increased. At pubertal age, at diagnosis, AMH and inhibin B were lower compared to the reference population for Tanner stage, with inappropriately normal FSH, suggesting a primary Sertoli cell dysfunction with insufficient gonadotrophin compensation. The LH-Leydig cell axis was mildly disrupted. After 3 months of chemotherapy, inhibin B and AMH were unchanged while median FSH levels rose to values that exceeded the reference range, indicating a significant impairment of Sertoli cell function. Testosterone normalized concomitantly with an abnormal LH elevation reflecting a compensated Leydig cell impairment. General health biomarkers were impaired at diagnosis and improved after 3 months.ConclusionThe HPT axis function is impaired in boys with hematopoietic malignancies before the initiation of chemotherapy. There is a primary testicular dysfunction and a concomitant functional central hypogonadism that could be due to an impaired overall health. The HPT axis function improves during the initial 3 months of chemotherapy concomitantly with the general health state. However, in pubertal boys the dysfunction persists as shown by elevated gonadotropin levels after 3 months.

【 授权许可】

Unknown   
Copyright © 2023 Lopez Dacal, Prada, Correa Brito, Ropelato, Ballerini, Rodriguez, Gutiérrez, Soria, Morán, Ferraro, Bedecarrás, Drelichman, Aversa, Bergadá, Rey and Grinspon