Long-term endocrine and testicular outcomes in male survivors of childhood acute lymphoblastic leukemia

Background and aim: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for long-term endocrine and gonadal dysfunction. While several studies have explored these risks in heterogeneous cancer survivor groups, data specific to ALL survivors remain limited. Herein, we aimed to evaluate late endocrine and gonadal effects in a homogeneous cohort of male childhood ALL survivors classified by risk groups, and to assess the predictive value of serum follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels for semen analysis outcomes. Methods: This cohort study included male survivors of childhood ALL treated between 2000 and 2020, classified as standard, intermediate, or high risk. Endocrine parameters, reproductive hormones, and semen analyses were evaluated. Results: Fifty-four survivors (mean age 17.5 ± 5.9 years) were included. Endocrine disorders were present in 40.7%, with obesity in 9.4%. Semen analysis (n = 33) revealed abnormal findings in 42.4% and azoospermia in 24.2%. The prevalence of gonadal dysfunction increased progressively from standard to high-risk groups. FSH thresholds of 3.55 mIU/mL was predictive of abnormal semen parameters (AUC: 0.88). AMH showed no predictive value for semen outcomes. Conclusions: This is the first study to evaluate gonadal outcomes through semen analysis in a homogeneous cohort of childhood ALL survivors stratified by risk group. Our findings support the use of FSH as a predictive marker of impaired spermatogenesis, while AMH appears to have no predictive value. The study also highlights the need for early reproductive counseling and consideration of fertility preservation strategies, especially in high-risk patients.