OR18-1 Leydig Cell Function in Adult Survivors of Childhood Cancer

Abstract

Context: Direct assessment of Leydig cell function in adult survivors of childhood cancer has been limited. Objectives: To describe the prevalence of, and risk factors for, Leydig cell failure (LCF) and associated adverse health outcomes. Design: Retrospective cohort with cross-sectional health outcomes analysis. Patients: 1534 participants (median age 30.8 years; range 18.1-63.8) evaluated at a median of 22.0 years (range 7.5-49.8) after cancer diagnosis. Survivors with LH/FSH deficiency were excluded. Main Outcome Measure: LCF was defined as serum total testosterone < 250 ng/dL (8.67 nmol/L) combined with LH >8.6 IU/L; compensated LCF by testosterone ≥ 250 ng/dL and LH >8.6 IU/L. Polytomous logistic regression evaluated associations between demographic and treatment-related risk factors and LCF or compensated LCF. Log-binomial regression examined associations between these diagnoses and risk of diabetes mellitus, dyslipidemia, abdominal obesity, frailty, erectile dysfunction, and psychological distress. Piecewise exponential models analyzed the association between mortality and LCF/compensated LCF. Results: The prevalence of LCF and compensated LCF was 8.0% (95% confidence interval (CI) 6.7%-9.4%) and 22.8% (95% CI 20.7%-25.0%), respectively. Individuals aged 36-45.9 years (odds ratio (OR) 3.8, 95% CI 1.9-7.9) or ≥46 years (OR 4.9, 95% CI 2.2-11.1) at the time of study had a significantly higher risk of LCF than those 18-25 years old. Participants treated with direct testicular radiotherapy at doses >0-19.9 (OR 81.6, 95% CI 24.9-266.7) or ≥ 20 Gy (OR >999, 95% CI 109.9->999) had a higher risk of LCF than those not exposed to this treatment. Individuals treated with alkylating agents at cyclophosphamide equivalent doses 4000-7999 mg/m2 (OR 3.6, 95% CI 1.9-6.9) or 8000-11999 mg/m2 (OR 3.7, 95% CI 1.9-7.3) or ≥ 12000 mg/m2 (OR 8.7, 95% CI 4.7-16.4) had a higher risk of LCF than those not exposed to these agents. LCF was independently associated with abdominal obesity (prevalence ratio (PR) 1.6, 95% CI 1.2-2.1), diabetes mellitus (PR 2.9, 95% CI 1.8-4.6), erectile dysfunction (PR 1.8, 95% CI 1.4-2.5), frailty (PR 2.5, 95% CI 1.2-5.3) and mortality (PR 4.8, 95% CI 2.3-10.1). For compensated LCF, the risk factor associations were similar to those found for LCF; however, no significant associations were found with adverse physical or psychosocial outcomes. Conclusion: In adult survivors of childhood cancer, older age, direct testicular radiotherapy and high dose alkylating agents were associated with LCF, which was associated with poor general health outcomes. Further studies are needed to investigate the role of sex hormone replacement in mitigating such outcomes.