Pubertal Gonadotrophin Levels Predict Future Testicular Function in Male Childhood Cancer Survivors: JAMA
According to a new study, Gonadotrophin levels measured during puberty serve as a reliable indicator of future adult testicular function in male childhood cancer survivors. It was further found that testicular impairment resulting from radiotherapy persists into adulthood, whereas testicular damage caused by alkylating chemotherapy shows evidence of recovery over time. Findings of research indicate that Sertoli cell–germ cell compartment demonstrates higher sensitivity to cancer treatments than Leydig cells. These insights provide a valuable basis for early risk assessment and personalized reproductive counseling in young male cancer survivors.
The study was published in JAMA Network Open by Mikael K. and colleagues. To explore associations between pubertal hormone levels and cancer treatments as well as adult fertility outcome variables, an examination of data was conducted by researchers between May and December 2025 from 221 male childhood cancer survivors diagnosed prior to age 17 years in the years 1964-2000. Treatment exposures were assessed on the basis of testicular radiotherapy dosage (in Gy) and alkylating agents exposures in terms of cyclophosphamide equivalent dose (CED, in g/m²).
Serial serum levels of the following reproductive hormones were determined biennially at ages of 12-18 years and again at 20 years and older: follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. The values obtained were transformed into age-adjusted z-scores.
Key findings:
- Hormonal effects in longitudinal tracking of the 221 male survivors (median age at diagnosis, 6.0 years [IQR, 3.2–11.7]) showed clear dose-related effects.
- At 18 years old, compared with patients who had received <4 g/m² CED (median FSH z score, 0.1), there were increased FSH z scores in those who received 4 to <12 g/m² CED (median z score, 1.4; P = 0.04) and ≥12 g/m² CED (median z score, 1.6; P = 0.007).
- In patients aged 20 or more years, FSH z scores returned to normal in the 4 to <12 g/m² CED group (median z score, 0.7) but persisted elevated in the ≥12 g/m² CED group (median z score, 1.7).
- The highest FSH z score at ages 14-16 years was the strongest predictor of adult azoospermia (AUC, 0.87), with the optimal cut-off values equal to 11.2 IU/L at age 14 and 12.5 IU/L at age 16.
- Elevated FSH z scores starting from age 12 were found in the patients with >1 Gy of testicular radiotherapy.
- Elevated LH z scores starting from age 12 years were found only in patients with >14 Gy of radiotherapy, whereas high CED exposure had no correlation with Leydig cell dysfunction.
In summary, the longitudinal cohort study proves that pubertal gonadotropin profiles are extremely useful in predicting future adult testicular function in male childhood cancer survivors. The results of the study reveal that despite radiotherapy being damaging, germ cell recovery is possible following moderate alkylating chemotherapy, making pubertal FSH an essential predictor of fertility.
Reference:
Koskela M, Duffin K, Korhonen M, et al. Pubertal Testicular Function in Childhood Cancer Survivors and Future Fertility. JAMA Netw Open. 2026;9(10):e2638294. doi:10.1001/jamanetworkopen.2026.38294
