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Yes—puberty hormones can provide an early warning about future fertility in some male childhood-cancer survivors, but they cannot determine an individual’s fertility on their own. In a 2026 Finnish cohort, the strongest signal was a high follicle-stimulating hormone (FSH) level at ages 14–16, particularly after testicular radiotherapy. Testosterone and physical pubertal development could remain relatively normal while sperm production was severely impaired.
What the new study found
Koskela and colleagues reported the study “Pubertal Testicular Function in Childhood Cancer Survivors and Future Fertility” in JAMA Network Open on October 9, 2026. The cohort included 221 males treated for childhood cancer before age 17 at Helsinki Children’s Hospital. Researchers measured serum FSH, luteinizing hormone (LH), and testosterone at two-year intervals from ages 12 through 18 and again at age 20 or older. They converted results to age-specific z scores and compared them with adult semen quality, paternity, testicular volume, and testosterone-replacement use.
The highest FSH result at ages 14–16 was associated with adult azoospermia—no sperm detectable in the ejaculate—among survivors who had received testicular radiotherapy. The study’s exploratory thresholds corresponded to 11.2 IU/L at age 14 and 12.5 IU/L at age 16, with an area under the receiver-operating-characteristic curve of 0.87. These values came from this cohort; they are not universal diagnostic cutoffs and should not be used to label someone sterile.
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1Scan for outdated or missing drivers - takes under a minute2Repair Windows errors before they cause bigger problems3Fix the driver behind crashes, sound loss and screen glitchesWhy FSH was more informative than testosterone
FSH reflects pituitary signaling to the Sertoli-cell and germ-cell compartment involved in sperm production. When that tissue is injured, the pituitary may increase FSH output. Leydig cells, which make testosterone, can be less sensitive to the same treatment. As a result, a survivor may enter and progress through puberty with apparently adequate testosterone while having substantial or irreversible impairment of sperm production.
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How to interpret each pubertal marker
| Marker | What it reflects | What a survivor should know |
|---|---|---|
| FSH | Pituitary stimulation of Sertoli cells and the germ-cell system | The most useful pubertal signal in the 2026 male cohort for later sperm-production risk. Persistent elevation is concerning, but one result cannot establish sterility. |
| LH | Pituitary stimulation of Leydig cells | Can rise because of primary testicular injury. The Endocrine Society cautions that “Elevated LH levels in such patients may be due to primary gonadal injury rather than to the onset of central puberty.” |
| Testosterone | Leydig-cell steroid production and pubertal progression | Normal levels support testosterone production but do not prove normal spermatogenesis. |
| Testicular volume | Physical growth of the testes | Useful in an examination, but not reliable as the sole pubertal marker after alkylating agents or direct testicular radiotherapy. |
How treatment exposure changes risk
Hormone results only make sense alongside the survivor’s treatment record. The relevant variables include the radiation field and dose, cumulative alkylating-agent exposure, hematopoietic stem-cell transplantation, radiation to the hypothalamus or pituitary, age at treatment, and combinations of these exposures. Combined treatments can have additive effects, so a guideline risk category is not the same as an individual fertility diagnosis.
Testicular radiotherapy
In the Helsinki cohort, FSH increased in a dose-dependent pattern after testicular radiotherapy. Elevation appeared from age 12 after exposure above 1 Gy. The association between the highest pubertal FSH and adult azoospermia was strongest in this treatment group.
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Alkylating chemotherapy
After an intermediate cumulative alkylating exposure of 4 to less than 12 g/m² cyclophosphamide-equivalent dose, FSH often moved toward the reference range by adulthood, suggesting that recovery may be possible for some survivors. At exposures of at least 12 g/m², elevation was more persistent. High cumulative alkylating exposure was not associated with impaired Leydig-cell function in this cohort, and testosterone varied less than FSH.
Brain-directed treatment and transplantation
Radiation affecting the hypothalamic-pituitary region can disrupt the signals that start or maintain puberty. Stem-cell transplantation and combined-modality therapy add further gonadal risk. A specialist must distinguish central hormone deficiency from direct testicular damage; the same LH or FSH value can have different meanings in those settings.
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What survivors and families should do
- Reconstruct the treatment exposure. Ask the survivorship team for radiation fields and doses, chemotherapy agents and cumulative doses, transplant history, and any hypothalamic-pituitary treatment.
- Review puberty over time. Clinicians should assess growth, symptoms, pubertal progression, and physical findings together with laboratory results. Serial measurements are more informative than a single hormone test.
- Use correctly timed blood tests. For boys at risk of central precocious puberty after gonadotoxic treatment, the Endocrine Society recommends morning testosterone and LH, preferably before 10 a.m. The appropriate timing and reference range depend on age and the laboratory.
- Escalate when results or exposure are concerning. Persistent FSH elevation, abnormal LH or testosterone, stalled or unusually early puberty, small or asymmetric testes, or high-risk treatment exposure warrants survivorship endocrinology review.
- Test fertility directly when the timing is appropriate. Adult or post-pubertal semen analysis, repeat testing when needed, and reproductive-endocrinology consultation provide information that hormone tests alone cannot. Paternity history and testicular examination add context but are not substitutes for semen testing.
- Discuss preservation and family-building options early. The 2023 German S1 guideline recommends individualized information and self-determined decisions about cryopreservation of sperm, germ cells, or germ-cell tissue when treatment or current findings indicate a possible fertility threat.
Does normal puberty mean fertility is normal?
No. Testosterone can remain comparatively preserved even when Sertoli-cell and germ-cell function is damaged. Conversely, an abnormal hormone result does not automatically mean permanent infertility; the Helsinki data suggest that some men with intermediate alkylating exposure may show biochemical recovery by adulthood. Fertility status requires the full treatment history, serial hormones, clinical examination, and—when medically appropriate—semen or ovarian-reserve assessment.
What about girls and women treated for childhood cancer?
The 2026 hormone-to-fertility analysis included males only. Its FSH thresholds must not be transferred to girls. Female survivors may need assessment based on pubertal development, menstrual history, FSH, LH, estradiol, and sometimes anti-Müllerian hormone. The appropriate evaluation depends on ovarian or pelvic radiation, alkylating exposure, transplant history, age at treatment, and hypothalamic-pituitary involvement.
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When guidelines recommend endocrine surveillance
The Endocrine Society recommends screening for LH and FSH deficiency in survivors exposed to at least 30 Gy of hypothalamic-pituitary radiation or to tumors or surgery affecting that region. Children’s Oncology Group long-term follow-up guidance lists delayed or arrested puberty, menstrual abnormalities, abnormal hormone levels, and treatment-related gonadal dysfunction as surveillance concerns. These recommendations identify who needs monitoring; they do not predict an individual’s ability to conceive.
Important limits of the evidence
- The direct study was male-only and conducted at one Finnish center.
- Participants were treated from 1964 through 2000, so therapies and laboratory assays changed over the study period.
- The registry-based analysis had limited subgroup sizes, and the ROC thresholds were exploratory.
- Brain-tumor patients treated at another hospital were excluded, which limits generalization to every survivor.
- No universal pubertal hormone thresholds were established for female survivors, every cancer diagnosis, or every treatment regimen.
The study’s conclusion is that monitoring testicular function during puberty can help assess later fertility and testosterone production, not that a hormone measurement replaces fertility testing. A childhood-cancer survivorship endocrinology clinic or fertility-preservation service can integrate exposure records, serial results, and reproductive goals into an individualized plan.
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