Background: Hypogonadism is the most frequent hormonal deficiency in individuals with Prader-Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. The aim of this audit was to evaluate the safety, tolerability and efficacy of testosterone treatment in individuals with PWS.
Methods: A retrospective audit was undertaken of individuals with PWS attending the Austin Health Weight Control Clinic between July 2010-April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and adverse effects.
Results: Data were available for 8 individuals with mean age 28.4 years (range 21-58) with BMI 44.8 kg/m2. Six men had obstructive sleep apnoea; none were smokers. Baseline total testosterone concentration was 2.6 nmol/L with haematocrit 0.43. Men were treated with testosterone for mean 6.0 years (range 1-12). Formulations were intramuscular (IM) testosterone undecanoate (TU) 1000mg (n=5), transdermal testosterone gel 50mg daily (n=1), and oral TU 80-120mg daily (n=2). Mean (SD) total testosterone concentration was 11.0 (4.5) nmol/L. Testosterone concentrations within the male reference range were only achieved with IM TU. Mean haematocrit during treatment was 0.47(0.04) with 9 (36%) >0.50. Three individuals with haematocrit >0.52 were treated with IM TU 1000mg every 12 weeks, with trough serum total testosterone 8.8-15.9 nmol/L. One individual had haematocrit >0.54 that necessitated decreased frequency of IM TU. IM TU was well tolerated whereas one individual discontinued testosterone gel due to poor compliance. Worsening behavioural disturbance with physical aggression resulted in treatment discontinuation in one individual, with subsequent improvement in behaviour.
Conclusions: Intramuscular TU achieved adequate serum testosterone concentrations and appears well tolerated in men with PWS but was complicated by polycythaemia, reinforcing the need for regular monitoring. Families and carers should be aware of the risk of worsening behavioural disturbance with testosterone treatment.