Radioactive iodine and male reproductive health in thyroid cancer survivors: evidence of delayed gonadal dysfunction

Purpose: Differentiated thyroid carcinoma (DTC) incidence is rising globally, with a higher prevalence in women. Male patients often present with more aggressive disease, leading to more frequent use of radioactive iodine (RAI) therapy. While the gonadotoxic effects of RAI in females have been studied, its impact on male reproductive health remains unclear. This study is aimed to assess the effects of RAI therapy on gonadal function in men with DTC, focusing primarily on follicle-stimulating hormone (FSH) serum levels as a biomarker of testicular function. Methods: We analyzed studies reporting FSH levels before and after RAI administration in male DTC patients. The primary outcome was the change in FSH levels over time, with secondary outcomes including luteinizing hormone (LH) levels and semen parameters. Results: Seven studies comprising 460 men met inclusion criteria. FSH levels significantly increased 12 months post-RAI (mean difference6.56 IU/L; p < 0.001), but not at 3 or 6 months. Meta-regression revealed that FSH elevation was positively associated with patient age and RAI dosage. No significant changes were observed in LH levels or standard semen parameters. Despite high heterogeneity (I²=99%), sensitivity analyses confirmed the findings. Conclusion: RAI therapy in male DTC patients is associated with delayed and dose-dependent increases in FSH, suggesting a potential subclinical impact on testicular function, particularly spermatogenesis. Standard semen parameters remain stable initially, possibly due to compensatory mechanisms. Powerful, prospective studies are needed to assess long-term reproductive outcomes and explore qualitative sperm alterations, including DNA integrity, to better inform fertility counseling in male DTC patients undergoing RAI.