Gonadal Hormone Substitution in People with Prader-Labhart-Willi Syndrome: An International Prader-Willi Syndrome Organisation Survey

Abstract

<b><i>Background:</i></b> Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction, and specific dysmorphisms. Hypothalamic dysfunction causes growth hormone deficiency, dysregulation of energy balance, and hypogonadism. Although hypogonadism is prevalent in PWS, there are no clear guidelines for diagnosis and treatment. In particular, gonadal hormone substitution is a matter of debate due to concerns associated with the potentially induced aggressive behaviour, foremost in males, by sex steroids. <b><i>Methods:</i></b> In 2019, a workshop dedicated to hypogonadism was held prior to the 10th International PWS Organization Conference. In this context, we designed a questionnaire to assess “the current standard of care” of hypogonadism in children and adults with PWS, which was sent out to physicians caring for people with PWS worldwide. <b><i>Results:</i></b> Responses were received from a total of 24 centres located in 19 countries. Participating centres treat a total number of at least 1,000 children and adults with PWS. Responses showed limited consensus on who should be treated or at what age treatment should commence. Remarkably, very few behavioural problems were attributed to hormone substitution. <b><i>Conclusion:</i></b> Based on our findings, we make recommendations to progress the knowledge on hypogonadism in PWS and improve daily practice.

Single‐center real‐life experience with testosterone treatment in adult men with Prader–Willi syndrome

“…Similarly, 4 of 24 individuals ceased testosterone treatment due to increasing behavioral disturbance in a recent analysis in people with PWS (Kherra et al, 2021), whereas another analysis reported behavioral disturbance in one‐third of individuals (Pellikaan et al, 2021). Few behavioral problems were attributed to testosterone treatment in a questionnaire of practitioners experienced in care of individuals with PWS (Eiholzer et al, 2021), and are not commonly reported in the literature following initiation of testosterone treatment (Noordam et al, 2021). Individuals with PWS are more prone to behavioral disturbances and aggressive outbursts (Tauber & Hoybye, 2021), so families should be counseled on the potential worsening of these behaviors following commencement of testosterone treatment (Heksch et al, 2017).…”