Evaluation of male reproductive function after aromatase inhibitor treatment during adolescence: case series with literature review

OBJECTIVES: Aromatase inhibitors (AIs) are widely used in clinical practice, including for the treatment of adolescents with short stature. However, their potential impact on the long-term reproductive function of male adolescents remains unclear. This exploratory study aimed to investigate this relationship. METHODS: We identified male patients with short stature who had completed AI therapy between 2015 and 2022 at the First Affiliated Hospital of Zhejiang University School of Medicine. A follow-up study was conducted in 2023 to assess semen parameters and retrospectively collect data on sex hormone levels and complications during the treatment period. RESULTS: Ten patients met the inclusion criteria and consented to participate. Of these, nine provided both semen and blood samples, while one provided only a blood sample. The median treatment duration was 1.93 years (range: 1.0-3.5 years), and the median age at treatment initiation was 12.7 years (range: 11-16 years). The median sperm concentration was 78.99 million/mL (range: 16.93-223.88 million/mL). The median acrosome integrity was 75.71 % (range: 30.9-93.4 %), and the median DNA fragmentation index (DFI) was 15.39 % (range: 8.62-25.72 %). Sex hormone levels for all patients were within normal ranges at follow-up, and the majority exhibited normal semen analysis results. CONCLUSIONS: In this case series study, the administration of aromatase inhibitors during adolescence was not associated with adverse effects on reproductive function parameters in early adulthood. These preliminary findings do not raise concerns regarding long-term reproductive safety. But larger, prospective studies are warranted for confirmation.