Assessment of testicular function in boys with hematological malignancies: a prospective longitudinal study.

Abstract

Survival after pediatric hematologic malignancies has improved substantially, increasing concern regarding endocrine sequelae. While gonadotoxic effects on germ cells are characterized in adult survivors, the early impact of cancer and chemotherapy on hypothalamic-pituitary-testicular axis during childhood and adolescence remains insufficiently studied. We conducted a prospective longitudinal cohort study including 63 boys and adolescents with acute lymphoblastic leukemia, acute myeloid leukemia, or non-Hodgkin lymphoma treated at a tertiary pediatric center in Argentina between 2013 and 2019. Hormonal markers of Sertoli cell (AMH, inhibin B, FSH) and Leydig cell function (testosterone, LH) were serially assessed from diagnosis, throughout chemotherapy, and up to 3 years after treatment completion. In prepubertal boys, Sertoli cell function was mildly impaired at diagnosis, with reduced AMH and FSH levels. AMH increased during induction chemotherapy, fluctuated during treatment, and normalized thereafter, remaining stable up to 3 years post-treatment. Transient FSH suppression coincided with exposure to high-dose corticosteroids. Boys entering puberty during follow-up showed persistently elevated AMH relative to pubertal stage, suggesting delayed Sertoli cell maturation. In pubertal patients, a transient seminiferous tubular dysfunction, reflected by increased FSH and decreased inhibin B occurred, with recovery by 3 years after treatment. Mild compensated Leydig cell dysfunction persisted, characterized by elevated LH despite normal testosterone concentrations. Testicular dysfunction associated with pediatric hematologic malignancies is mostly reversible. However, delayed Sertoli cell maturation and persistent compensated Leydig cell insufficiency indicate residual testicular vulnerability, underscoring the importance of long-term endocrine surveillance during and after the end of chemotherapy.