Pubertal FSH Associated With Adult Azoospermia in Childhood Cancer Survivors

A cohort study at Helsinki Children’s Hospital examined whether pubertal reproductive hormones were associated with adult gonadal outcomes in 221 male childhood cancer survivors. Participants were diagnosed before age 17 years between 1964 and 2000; median age at diagnosis was 6.0 years. Researchers assessed age-standardized follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations during puberty and adulthood, alongside alkylating chemotherapy exposure and testicular radiotherapy.

FSH elevations appeared from age 12 years after testicular radiation doses exceeding 1 Gy. At age 18, median FSH z scores were 0.1 for cyclophosphamide equivalent doses (CED) below 4 g/m², 1.4 for 4 to less than 12 g/m², and 1.6 for at least 12 g/m². In adulthood, the intermediate-exposure group showed evidence of normalization, whereas elevations persisted in the highest-exposure group. The highest FSH z score at ages 14–16 was associated with adult azoospermia, with an area under the curve of 0.87. Optimal cutoffs corresponded to 11.2 IU/L at age 14 and 12.5 IU/L at age 16.

LH elevations occurred from age 12 after radiation doses exceeding 14 Gy; high CED was not associated with impaired Leydig cell function. These findings may inform reproductive counseling, but the observational, single-center cohort reflects historical treatment exposures. The abstract does not report the number assessed for adult azoospermia or external validation of the proposed thresholds, limiting their interpretation for individual prognostication.