ESPE Yearbook of Paediatric Endocrinology

Cancer. 2025 Jan 1;131(1):e35623. PMID: 39470456. doi: 10.1002/cncr.35623. [email protected]

Brief summary: This retrospective study evaluated the long-term effects of prior cancer treatments, such as chemotherapy and radiotherapy, on testicular volume, sperm quality and paternity outcomes in 255 male childhood cancer survivors (CCS) who were treated at Helsinki Children’s Hospital between 1964 and 2000, from adolescence to adulthood.

Testicular volume was monitored from puberty into adulthood, and semen analyses with hormonal measurements (FSH, LH, inhibin B and testosterone) were performed after age 20. Treatment exposures, including cumulative alkylating agent dose (cyclophosphamide equivalent dose, CED) and testicular radiation, were documented. Outcomes such as testicular volume (Z score), sperm quality, and paternity were then compared between treatment subgroups (such as chemotherapy only vs. chemotherapy plus radiotherapy).

Patients treated with chemotherapy alone showed a delayed but eventual return of their testis volume to normal levels, while those exposed to testicular radiation ≥1 Gy had persistently reduced volumes. Increased risk of azoospermia and lower paternity rates was observed with high-dose alkylating agents (CED ≥12 g/m²) and testicular radiation. A testicular volume z-score <−2 strongly predicted azoospermia, and hormonal markers (elevated FSH, low inhibin B) further supported gonadal dysfunction. Improvements in semen parameters over time were most evident in the chemotherapy-only groups.

Comment: This study investigated the different impacts of chemotherapy and radiotherapy on male fertility. The results highlight that testicular volume measurements and serum hormone levels, such as FSH and inhibin B, can predict the risk of azoospermia. These findings underscore the importance of long-term monitoring and fertility counseling in male CCS exposed to gonadotoxic treatments.