Leydig Cell Function in Male Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study

Abstract

PURPOSE Direct assessment of Leydig cell function in childhood cancer survivors has been limited. The objectives of this study were to describe the prevalence of and risk factors for Leydig cell failure (LCF), Leydig cell dysfunction (LCD), and associated adverse health outcomes. PATIENTS AND METHODS In this retrospective study with cross-sectional health outcomes analysis, we evaluated 1,516 participants (median age, 30.8 years) at a median of 22.0 years after cancer diagnosis. LCF was defined as serum total testosterone less than 250 ng/dL (or 8.67 nmol/L) and luteinizing hormone greater than 9.85 IU/L, and LCD by testosterone as 250 ng/dL or greater and luteinizing hormone greater than 9.85 IU/L. Polytomous logistic regression evaluated associations with demographic and treatment-related risk factors. Log-binomial regression evaluated associations with adverse physical and psychosocial outcomes. Piecewise exponential models assessed the association with all-cause mortality. RESULTS The prevalence of LCF and LCD was 6.9% and 14.7%, respectively. Independent risk factors for LCF included an age of 26 years or older at assessment, testicular radiotherapy at any dose, and alkylating agents at cyclophosphamide equivalent doses of 4,000 mg/m2 or greater. The risk increased with older age, higher doses of testicular radiotherapy, and cyclophosphamide equivalent doses. LCF was significantly associated with abdominal obesity, diabetes mellitus, erectile dysfunction, muscle weakness, and all-cause mortality. LCD was associated with unilateral orchiectomy and the same risk factors as LCF; no significant associations were found with adverse physical or psychosocial outcomes. CONCLUSION Older age, testicular radiotherapy, and exposure to alkylating agents were associated with LCF, which was associated with adverse physical and psychosexual outcomes. LCD, 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.

Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

“…15,16 Despite the heterogeneity of the cohorts evaluated in different studies, the prevalence of spermatogenesis damage and LCF observed in our cohort was similar to those reported in literature data. [24][25][26] In females, we found a 26.2% cumulative incidence of POI, which is higher than that recently observed in a wide cohort of CCS. 27 gonadal failure after exposure to TBI, in both males and females.…”

Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

“…Of 2932 articles identified, 546 were subjected to a full text review and 30 were eligible, including the evidence described in the previous IGHG publication 5 (Figure 1). The conclusions of evidence and the EtD-frameworks tables are presented in the appendix (p. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. The recommendations are presented in Figure 2 and the appendix (p. [39][40][41][42].…”

Restorative functions of Autologous Stem Leydig Cell transplantation in a Testosterone-deficient non-human primate model

“…Chemotherapy and radiation treatments for cancer or other conditions can result in the loss of both spermatogenesis and LC function 81 . Therefore, most patients suffer from TD, increased body fat, decreased libido and infertility 82 .…”