FERTILITY after childhood cancer was associated with reproductive hormone levels during puberty in a cohort study of 221 male survivors, with testicular radiotherapy linked to persistent testicular impairment and evidence of hormonal recovery after intermediate-dose alkylating chemotherapy. The findings suggest that monitoring reproductive hormones during adolescence could help identify survivors who may benefit from early fertility counselling.
Pubertal Hormones and Future Fertility
Researchers investigated the relationship between pubertal hormone levels, previous cancer treatment, and adult testicular function. The cohort included male survivors diagnosed with cancer before the age of 17 years between 1964 and 2000.
Hormone measurements included follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone, assessed at two-year intervals between ages 12 and 18 years and in adulthood. Treatment exposures included testicular radiotherapy and alkylating chemotherapy, quantified using cyclophosphamide equivalent dose.
Radiotherapy and Adult Azoospermia
FSH levels increased in a dose-dependent pattern following testicular radiotherapy, with elevated levels observed from age 12 years among survivors who received more than 1 Gy. Higher FSH levels during puberty were associated with azoospermia in adulthood, defined as the absence of sperm in semen.
The researchers identified optimal FSH thresholds corresponding to 11.2 IU/L at age 14 years and 12.5 IU/L at age 16 years for predicting adult azoospermia. The predictive analysis achieved an area under the curve of 0.87. Elevated LH levels were also observed from age 12 years among survivors who received more than 14 Gy of radiotherapy. Overall, radiotherapy-associated testicular impairment persisted into adulthood.
Hormonal Recovery After Chemotherapy
At age 18 years, FSH levels were higher among survivors who received intermediate or high cumulative doses of alkylating chemotherapy than among those who received less than 4 g/m². However, evidence of normalisation emerged in adulthood among those receiving intermediate doses of 4 to less than 12 g/m². This recovery was not observed among survivors who received 12 g/m² or more.
High cumulative chemotherapy exposure was not associated with impaired Leydig cell function, which contributes to testosterone production. The findings suggest that sperm-producing cells may be more sensitive to treatment-related damage than testosterone-producing cells.
The authors concluded that pubertal hormone measurements could help inform fertility counselling for male childhood cancer survivors. Further validation is needed before the proposed FSH thresholds can be routinely applied in clinical practice.
Reference
Koskela M et al. Pubertal testicular function in childhood cancer survivors and future fertility. JAMA Netw Open. 2026;9;(10):e2638294.
