The Use of Growth Hormone Therapy in Adults With Prader-Willi Syndrome

A Systematic Review

Mikaela Frixou; Diane Vlek; Angela K. Lucas-Herald; Lindsay Keir; Andreas Kyriakou; M. Guftar Shaikh


Clin Endocrinol. 2021;94(4):645-655. 

In This Article

Abstract and Introduction


Objective: Despite clear benefits in the management of children with Prader–Willi syndrome (PWS), the role of growth hormone (GH) in adults is unclear. The aim of this study was to conduct a systematic review to evaluate the effects of GH on body composition, bone health and cardiovascular health in adults with PWS.

Design: A systematic computerized literature search of the PubMed database was conducted by two independent reviewers. Inclusion criteria were individuals over the age of 16 years with a genetic diagnosis of PWS who had received GH therapy, together with assessment of body composition, bone health or cardiovascular health.

Results: Twenty full-text papers met the inclusion criteria, encompassing 364 unique patients. No differences in body mass index (BMI) were noted, although 2 studies reported increased BMI after GH cessation. Data demonstrated statistically significant increases in lean body mass and reductions in percentage fat mass. Studies reported inconsistent effects of GH on cholesterol and echocardiography parameters. No studies reported differences in bone mineral density, although one reported improved bone geometry. Minor adverse events including pretibial oedema, headache and transient impaired glucose tolerance were reported in 7 studies.

Conclusions: These data suggest that GH is safe and well tolerated in adults with PWS, with evidence of improvement in body composition. Further longitudinal studies are still required to investigate the effects of GH on bone and cardiovascular health. Where GH is used in adults with PWS, this should be managed by a specialist multidisciplinary team with regular monitoring initiated.


Prader-Willi syndrome (PWS) is a condition with a prevalence of between 1 in 10,000 and 1 in 30,000,[1,2] which can arise from deletion of the paternal chromosome 15 (del15q11-q13), maternal uniparental disomy of chromosome 15 (UPD15) or genetic imprinting errors.[3] Children with PWS have altered body composition, with generally lower lean body mass (LBM) and higher fat mass (FM) percentages than healthy individuals.[4–6] Patients with PWS have hyperphagia, reduced muscle mass and exercise capacity, which can lead to obesity, further exacerbating the abnormal body composition and resulting in a high rate of comorbidities including metabolic syndrome and hepatic steatosis.[3] A high incidence of osteoporosis at younger ages is also observed in PWS patients, and it is estimated that between 60% and 90% of these individuals become osteoporotic in their lifetime with high rates of associated scoliosis requiring intervention.[7]

The high incidence of obesity in PWS contributes to the development of many cardiovascular risk factors, including the development of type 2 diabetes mellitus (T2DM), abnormal lipid profiles and high blood pressure (BP).[3] Adults with PWS are also known to have higher rates of electrical and structural cardiac abnormalities than healthy adults, with evidence of microvascular dysfunction.[8]

Growth hormone levels are low in 60%-100% of children with PWS, and GH replacement therapy has been licensed for use in children since 2000.[9] Although PWS children tend to have short stature, the indication for GH therapy is not to primarily increase height, but rather to help to improve body composition and increase LBM, which may subsequently reduce hypotonia and therefore increase muscle and motor function.[9] More recently, studies have even demonstrated higher vocabulary IQ scores in paediatric PWS patients treated with GH compared with non-GH groups.[10] In previously treated young adults with PWS, approximately 1 in 7 demonstrated GH insufficiency on GHRH-arginine testing, but none fulfilled the consensus criteria for adult GHD.[11]

A meta-analysis published in 2012 demonstrated that GH may improve body composition in adults with PWS.[12] In addition, a previous review by our group suggested that continuous GH use is beneficial in adolescents.[13] However, currently GH use in adulthood is not licensed unless there is confirmed GHD. Consequently, when transitioning to adult endocrine services, GH therapy is likely to be discontinued.

The aim of this systematic review was to update the current literature by summarizing the findings of all studies exploring GH use in adults with PWS, and its effects on body composition, bone and cardiovascular health. As a secondary objective, the safety of using GH in adults and data regarding the reported side effects for patients on treatment were also collated.