Childhood Cancer: puberty hormones may predict fertility risks
A study of 221 male childhood cancer survivors found that hormone levels during puberty may help identify future fertility problems, particularly after testicular radiotherapy.
Male childhood cancer survivors may face fertility problems later in life, but hormone measurements during puberty could help identify those at greater risk, according to a study published in JAMA Network Open on October 9, 2026.
The study examined 221 male survivors and found that elevated follicle-stimulating hormone (FSH) levels during adolescence were associated with azoospermia in adulthood, a condition in which semen contains no sperm.
The findings suggest that monitoring reproductive hormones during puberty may help doctors provide earlier fertility counselling to survivors of childhood cancer.
How Researchers Studied Future Fertility
Researchers examined male patients who had been diagnosed with cancer before age 17 and treated at Helsinki Children's Hospital between 1964 and 2000.
The study assessed reproductive hormone measurements taken during puberty and adulthood, alongside previous cancer treatments and adult reproductive outcomes.
The researchers focused on two treatment exposures: testicular radiotherapy and alkylating chemotherapy, which can affect the body's ability to produce sperm.
They found that hormone patterns during puberty differed according to the type and intensity of cancer treatment received.
Radiotherapy Linked to Persistent Fertility Problems
Testicular radiotherapy was associated with higher FSH levels, with increases observed from age 12 among survivors who received more than 1 gray (Gy) of radiation.
Higher FSH levels during puberty were associated with an increased likelihood of azoospermia in adulthood. The study identified levels corresponding to 11.2 IU/L at age 14 and 12.5 IU/L at age 16 as the optimal thresholds for distinguishing survivors with this outcome within the study.
The analysis achieved an area under the curve of 0.87, indicating that FSH measurements showed good ability to distinguish between those with and without azoospermia in this cohort.
The researchers also found that testicular radiation exposure was associated with persistent impairment of testicular function into adulthood.
However, the proposed hormone thresholds require further validation and should not be treated as definitive diagnostic cutoffs for every patient.
Some Hormone Changes May Recover After Chemotherapy
The study also identified different patterns among survivors who received alkylating chemotherapy.
FSH levels were elevated during late puberty among patients who received intermediate or high cumulative chemotherapy doses. However, levels showed evidence of returning toward the normal range in adulthood among those who received intermediate doses of 4 to less than 12 grams per square meter.
This pattern of recovery was not observed in the group receiving 12 grams per square meter or more, in whom FSH levels remained elevated into adulthood.
The findings suggest that some treatment-related changes in sperm-producing function may improve over time, although recovery is not guaranteed.
Sperm Production and Testosterone Function
The researchers found that the sperm-producing part of the testis appeared more sensitive to cancer treatment than the cells responsible for testosterone production.
Although some survivors had elevated reproductive hormones associated with impaired testicular function, testosterone levels remained largely within the normal reference range across treatment groups.
This distinction is important because normal testosterone production and progression through puberty do not necessarily mean that sperm production or fertility is unaffected.
What the Findings Mean for Cancer Survivors
The researchers concluded that reproductive hormone monitoring during puberty may help identify male childhood cancer survivors who could benefit from early fertility counselling.
The study also highlights differences between the potential long-term effects of radiotherapy and chemotherapy, suggesting that follow-up should consider each patient's treatment history.
However, the study was observational and included a relatively small group of survivors. Its findings support further research into monitoring strategies rather than establishing a universal method for predicting fertility.
