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Effects of Growth Hormone Treatment on Sleep-Related Parameters in Adults With Prader-Willi Syndrome
Hasanain Hamid Shukur1, Laith Hussain-Alkhateeb2, Stense Farholt3
1Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Solna SE-171 76, Sweden.
Insights
Growth hormone (GH) treatment in adults with Prader-Willi syndrome (PWS) improved sleep efficiency. No significant negative impact on respiration was observed, suggesting GH is safe for PWS patients regarding sleep and breathing.
Area of Science:
- Genetics and Endocrinology
- Neurodevelopmental Disorders
- Sleep Medicine
Background:
- Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by hypotonia, hyperphagia, obesity, and neurodevelopmental issues.
- Sleep disturbances, including sleep apnea, are prevalent in PWS patients.
- Growth hormone (GH) deficiency is common in PWS, and GH therapy is used, but its respiratory effects are a concern.
Purpose of the Study:
- To evaluate the impact of GH treatment on polysomnographic measurements in adults with PWS.
- To assess the safety and efficacy of GH therapy concerning sleep and respiratory function in PWS.
Main Methods:
- A 1-year randomized controlled trial involving 37 adults with PWS, comparing GH treatment to placebo.
- Polysomnography was conducted every 6 months to monitor sleep and respiratory parameters.
- Mixed-effect regression models were used for longitudinal data analysis.
Main Results:
- Growth hormone (GH) treatment did not significantly alter sleep or respiratory parameters compared to placebo.
- Sleep efficiency (SE) showed continuous improvement during GH treatment, even after adjusting for body mass index (BMI).
- The apnea-hypopnea index (AHI) showed inconsistent increases within the normal range, and no clinically significant negative respiratory impact was observed.
Conclusions:
- GH treatment in adults with PWS leads to improved sleep efficiency without clinically significant adverse effects on respiration.
- The multifactorial nature of breathing disorders in PWS necessitates ongoing awareness, irrespective of GH treatment status.
Context:
Prader-Willi syndrome (PWS) is a rare, genetic, multisymptom, neurodevelopmental disease due to lack of the expression of the paternal genes in the q11 to q13 region of chromosome 15. The main characteristics of PWS are muscular hypotonia, hyperphagia, obesity, behavioral problems, cognitive disabilities, and endocrine deficiencies, including growth hormone (GH) deficiency. Sleep apnea and abnormal sleep patterns are common in PWS. GH treatment might theoretically have a negative impact on respiration.
Objective:
Here we present the effect of GH treatment on polysomnographic measurements.
Methods:
Thirty-seven adults, 15 men and 22 women, with confirmed PWS were randomly assigned to 1 year of GH treatment (n = 19) or placebo (n = 18) followed by 2 years of GH treatment to all. Polysomnographic measurements were performed every 6 months. A mixed-effect regression model was used for comparison over time in the subgroup that received GH for 3 years.
Results:
At baseline median age was 29.5 years, body mass index 27.1, insulin-like growth factor 115 µg/L, apnea-hypopnea index (AHI) 1.4 (range, 0.0-13.9), and sleep efficiency (SE) 89.0% (range, 41.0%-99.0%). No differences in sleep or respiratory parameters were seen between GH- and placebo-treated patients. SE continuously improved throughout the study, also after adjustment for BMI, and the length of the longest apnea increased. AHI inconsistently increased within normal range.
Conclusion:
SE improved during GH treatment and no clinical, significantly negative impact on respiration was seen. The etiology of breathing disorders is multifactorial and awareness of them should always be present in adults with PWS with or without GH treatment.
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