ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Oncol. 2019;37(32):3018–3031. wassim.chemaitilly@stjude.org

This retrospective study, with cross-sectional health outcomes analysis, evaluated Leydig cell function in 1516 childhood cancer survivors at a median duration of 22.0 years after cancer diagnosis. These patients are part of the St Jude Lifetime Cohort. An age- and sex-matched community control group was recruited among friends and relatives of patients. Leydig cell failure (LCF) was defined as serum total testosterone <250 ng/dl and LH >9.85 IU/l, while Leydig cell dysfunction (LCD) was defined as testosterone ≥250 ng/dl and LH >9.85 IU/l. Follow-up data were available on 683 participants (45.2%). The point prevalence of LCF and LCD at the most recent evaluation was 6.9% and 14.7%, respectively; 42/104 patients with LCF (40.4%) used hormone replacement therapy. Eight controls, (4.8%) were receiving testosterone, but the indications for treatment were not available. No control had LCF, while 4 individuals had LCD. Independent risk factors for LCF included: age ≥26 years at assessment, testicular radiotherapy, and alkylating agents at cyclophosphamide equivalent doses ≥4000 mg/m². LCF was also associated with: abdominal obesity, diabetes mellitus, erectile dysfunction (ED), muscle weakness, and all-cause mortality. Hormone-treated LCF was associated with increased waist circumference, ED, muscle weakness, and depression, but not with all-cause mortality. LCD was associated with unilateral orchiectomy and the same risk factors as LCF. No significant associations of LCF and LCD with adverse physical or psychosocial outcomes were found.

The study reveals that despite the availability of hormonal replacement therapy, only a minority (40.4%) of patients with LCD receive such treatment. On the other hand, many of the associations between LCF and long-term adverse physical and psychosexual health outcomes persisted even among individuals who reported to be treated with hormonal replacement therapy. The selection of control subjects may be questioned, as some of them were treated with testosterone for unclear reasons. Finally, the cohort of survivors was not homogeneous, but included patients with different cancer diagnoses and prevalence estimates have to be interpreted with caution, given the substantial number of nonparticipants.