ESPE Abstracts

Introduction: Hypogonadism affects almost all males with Prader-Willi syndrome (PWS) and is associated with decreased bone mineral density (BMD). Testosterone Replacement Therapy (TRT) improves BMD and aids sexual maturation, but TRT could aggravate challenging behaviour that many patients with PWS already suffer from, causing reluctance in starting TRT in males with PWS. This study aims to provide more evidence on the effect of TRT on behaviour, BMD and body composition in adolescents and young adults with PWS.

Design: Longitudinal, prospective, observational study of a Dutch PWS cohort.

Participants: Fifty-nine male PWS patients treated with growth hormone, aged >14 years.

Methods: TRT was initiated at a low dose and was slowly increased. Behaviour was assessed by the Developmental Behaviour Checklist - Parents (DBC-P). Reasons for not starting TRT and course of TRT were extracted from paper and electronic patient records. Dual energy X-ray absorptiometry scans were performed, measuring BMD of the lumbar spine (BMD_LS) and of the total body (BMD_TB), lean body mass (LBM) and fat mass percentage (FM%).

Results: In this cohort of 59 patients with a median (IQR) age of 22.57 (18.46 – 26.35) years, 44 had used TRT. Spontaneous ongoing pubertal progression was the most common reason not to start TRT (n =8), followed by parents’ fear of challenging behaviour (n =2). Median age at TRT initiation was 16.6 years. Transdermal testosterone was the most common route of administration (72.7%). Three patients (6.8%) ceased TRT permanently due to challenging behaviour, after which behaviour improved in two patients. In 30 patients (68.2%), there was no challenging behaviour necessitating a dose change or cessation. In the remaining patients, TRT dose was (temporarily) not increased (n = 5), lowered (n = 1), or temporarily ceased (n = 5). 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 – 0.54; P =0.107) BMD_LS and -0.28 (-0.50 – -0.06; P =0.014) BMD_TB after 5 years. LBM SDS increased by 0.47 (95% CI: 0.15 – 0.79; P =0.005) after 5 years. Two years after TRT initiation, mean (95% CI) FM% had decreased significantly by 4.45 (-6.42 – -2.48; P <0.001) percentage points (-0.31 SDS from baseline; -0.44 – -0.19; P <0.001), but after 5 years, FM% was not different compared to baseline (P =0.132).

Conclusion: Under close surveillance, Testosterone Replacement Therapy is an efficacious method to maintain bone mineral density and improve body composition in hypogonadal adolescents and young adults with PWS, with little effect on behaviour.