Long-term growth hormone effects in Prader-Willi syndrome: A systematic review and meta-analysis

To assess the long-term effects and mortality rates associated with GH therapy in patients with Prader-Willi Syndrome (PWS). Prader-Willi Syndrome is a rare genetic disease characterized by growth hormone (GH) deficiency among other endocrine disorders.

A systematic literature search was carried out on 4 databases including PubMed, Scopus, Web of Science, and Cochrane databases. The search was based on two keywords: "Growth hormone" AND "Prader-Willi Syndrome". Outcome data included height-standard deviation score (SDS), weight SDS, body mass index (BMI)-SDS, insulin like growth factor 1 (IGF1), mortality, low density lipoprotein (LDL)-cholesterol, and blood glucose.

A total of 41 studies were included, of which 30 were involved in the meta-analysis. Following treatment with GH, height-SDS showed a significant increase compared to baseline in two timeline subgroups (≤2 years and >2 years), with a mean difference (MD) of 1.05 (95% CI: 0.92-1.18, p<0.00001) and 1.53 (95% CI: 1.23-1.82, p<0.00001), respectively. Patients on GH experienced a more pronounced increase in height-SDS compared to those who have not received GH. This was further associated with a lower BMI-SDS among GH-treated patients compared to their counterparts, with an MD of -1.02 (95% CI: -1.76 to -0.28, p=0.007; I²=84%, p=0.0003). Additionally, IGF1-SDS showed a marked increase after GH. Other metabolic effects include significant increase in LDL and blood glucose levels after GH treatment. The mortality rate in PWS patients undergoing GH treatment is estimated at 1.5% (95% CI: 0.8-2.2%), with causes including respiratory issues, cardiac arrest, infections, accidents, and gastrointestinal complications.

GH therapy in PWS significantly improves height and IGF-1 SDS, while relatively decreasing BMI compared to no-GH, indicative of lean mass growth and healthy development. Nonetheless, GH therapy requires careful metabolic monitoring due to its mixed effects on cholesterol and glucose levels.PROSPERO Reg. number: CRD420250649945.