In a retrospective analysis from the St. Jude Lifetime Cohort Study reported in the Journal of Clinical Oncology, Chemaitilly et al identified the prevalence of and risk factors for failure and dysfunction of Leydig cells, which are responsible for testosterone secretion, and associated adverse health outcomes in male survivors of childhood cancer.
"Additional studies are needed to investigate the role of sex hormone replacement in mitigating the burden from adverse outcomes in survivors.”— Chemaitilly et al
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Study Details
The study involved 1,516 patients with a median age of 30.8 years old evaluated at a median of 22.0 years after cancer diagnosis (minimum eligible age of 18 years old and minimum of 5 years follow-up since diagnosis). Leydig cell failure was defined as serum total testosterone < 250 ng/dL and luteinizing hormone > 9.85 IU/L; Leydig cell dysfunction was defined as testosterone ≥ 250 ng/dL and luteinizing hormone > 9.85 IU/L.
Prevalence of Failure, Risk Factors, and Adverse Health Outcomes
Overall, the prevalence of Leydig cell failure was 6.9% and the prevalence of Leydig cell dysfunction was 14.7%.
KEY POINTS
- Leydig cell failure was associated with increased risk of abdominal obesity, diabetes mellitus, erectile dysfunction, muscle weakness, and all-cause mortality.
- Leydig cell dysfunction was not significantly associated with increased risk of adverse health outcomes.
On multivariate analysis, independent risk factors for Leydig cell failure included age ≥ 26 years old at assessment, testicular radiotherapy at any dose, and alkylating agents at cyclophosphamide equivalent doses of ≥ 4,000 mg/m2. Risk increased with older age, higher doses of testicular radiotherapy, and higher cyclophosphamide equivalent doses. Patients with Leydig cell failure were significantly more likely (all P < .01) to have abdominal obesity (prevalence ratio [PR] vs patients with normal cell function = 1.9), diabetes mellitus (PR = 3.0), erectile dysfunction (PR = 1.9), muscle weakness (PR = 2.6), and all-cause mortality (rate ratio = 4.9).
Independent risk factors for Leydig cell dysfunction included age ≥ 26 years at assessment, testicular radiotherapy at doses ≥ 12 Gy, cyclophosphamide equivalent doses ≥ 4,000 mg/m2, and unilateral orchiectomy. No significant associations were found between Leydig cell dysfunction and adverse physical or psychosocial outcomes.
The investigators concluded, “Older age, testicular radiotherapy, and exposure to alkylating agents were associated with Leydig cell failure, which was associated with adverse physical and psychosexual outcomes. Leydig cell dysfunction, although having similar risk factors, was not associated with adverse health outcomes. Additional studies are needed to investigate the role of sex hormone replacement in mitigating the burden from adverse outcomes in survivors.”
Wassim Chemaitilly, MD, of the Department of Pediatric Medicine, Division of Endocrinology, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
