Long-Term endocrine outcomes with special emphasis on the gonadal impact of acute lymphoblastic leukemia treatment in females

This study aims to explore the long-term endocrine and gonadal effects of chemotherapy and radiotherapy in female acute lymphoblastic leukemia (ALL) patients. A cohort study included girls diagnosed with ALL and treated between 2000 and 2020. Patients with at least 2 years elapsed since treatment completion were included. Endocrinological evaluations included anthropometric measures and pubertal status, as well as fasting insulin, glucose, lipid levels, and hormone assessments for adrenal, and thyroid functions. Reproductive functions were evaluated based on gonadotropin, estradiol, and anti-Müllerian hormone (AMH) levels. A total of 51 female patients were included. At the time of study participation, the mean age was 14.7 years, and the mean time since treatment completion was 9.4 years. At least one endocrine disorder was present in 39.2% of participants, with dyslipidemia, insulin resistance, and obesity being the most common. Low AMH levels (< 1.1 ng/dL) were found in 41.6%, particularly in those who underwent bone marrow transplantation. A significant positive correlation was found between the time elapsed since treatment and AMH levels (p < 0.001, r = 0.612), while age at diagnosis, risk group (standard, intermediate or high risk), and cranial radiotherapy showed no significant associations. A substantial proportion of ALL survivors developed endocrine complications, with ovarian reserve compromised in over 40% of cases. Notably, this is the first cohort study to demonstrate a significant positive correlation between AMH levels and the time elapsed since treatment, suggesting a potential for gonadal recovery except in those exposed to intensive chemotherapy or transplantation.