Testosterone Replacement Therapy in Adolescents and Young Adults With Prader‐Willi Syndrome: Efficacy and Effects on Behaviour

ABSTRACT Context Hypogonadism in Prader‐Willi syndrome (PWS) is associated with decreased bone mineral density (BMD) in male adolescents and adults. Testosterone Replacement Therapy (TRT) improves BMD and sexual maturation, but TRT could aggravate pre‐existing challenging behaviour in male patients with PWS. Objective To investigate the effect of TRT on behaviour, BMD and body composition in adolescents and young adults with PWS. Design Longitudinal observational study in a Dutch PWS cohort. Participants Fifty‐nine male patients with PWS on growth hormone treatment, aged > 14 years. Methods Behaviour was assessed by the Developmental Behaviour Checklist‐Parents(DBC‐P). Dual energy X‐ray absorptiometry scans were performed, measuring BMD of the lumbar spine (BMD LS ) and total body (BMD TB ), lean body mass (LBM) and fat mass percentage (FM%). Results 59 patients with a median (IQR) age of 22.57 (18.46–26.35) years, of which 44 used TRT. Median age at TRT initiation was 16.6 years. Three patients (6.8%) discontinued TRT permanently due to challenging behaviour. In 30 patients (68.2%), there was no behaviour necessitating a dose change or discontinuation. DBC‐P total score did not significantly change during TRT. BMD SDS stabilised following TRT initiation, with a mean (95% CI) BMD SDS difference from baseline of 0.24 (−0.06 to 0.54; p = 0.107) BMD LS and −0.28 (−0.50 to −0.06; p = 0.014) BMD TB after 5 years. LBM SDS improved and FM% SDS remained similar. Conclusion Under close surveillance, TRT is an efficacious method to maintain BMD and improve body composition in hypogonadal male patients with PWS, with minor effects on behaviour in most cases.