Growth Hormone May Help Adults Sleep Better Without Raising Apnea Risk
In adults with Prader-Willi syndrome (PWS), use of growth hormone (GH) treatment may improve the quality of sleep with no significant negative effects on breathing, such as obstructive sleep apnea, a Scandinavian study suggested.
Sleep-related breathing disorders (SRBDs), which include central and obstructive apnea, are frequent in people with PWS.
Obstructive sleep apnea occurs when throat muscles intermittently relax, and completely or partly block the airways during sleep. It affects as many as 80% of children with PWS, and moderate to severe obstructive sleep apnea has a reported prevalence of 22% in adult patients.
Central sleep apnea, in contrast, arises when the brain temporarily fails to send signals to the muscles that control breathing. This type of SRBD mostly affects infants with PWS.
Possible causes for SRBDs include excess weight, decreased muscle tone, birth defects of the face or head, and enlarged tonsils and adenoids.
In adults with PWS, growth hormone deficiency is common, and studies have shown its use as a treatment benefits patients’ physical capabilities and quality of life. But information on how GH affects measures of breathing and sleep in adults with PWS is lacking.
“Based on our clinical experience and previous studies we hypothesized that GH treatment would unlikely impair breathing or sleep parameters,” the team wrote.
A clinical trial (NCT00372125), sponsored by researchers with Karolinska University Hospital in Sweden, enrolled 37 adults with PWS (median age of 29.5) across Scandinavian countries. All were new to GH treatment or had used it only in childhood.
The study, which ran from 2005 to 2010, had two parts: random assignment to GH treatment or a placebo for one year, followed by open-label GH treatment for all enrolled over the next two years.
Nineteen patients, seven men and 12 women, were randomized to GH, given either as 0.3 mg or 0.4 mg daily (depending on body weight below or above 100 kg; about 220 lbs) for the first four weeks. Doses were then increased to 0.6 mg/day or 0.8 mg/day for the following 11 months. The other 18 patients, eight men and 10 women, received a placebo.
After the first year, the GH dose was adjusted according to insulin-like growth factor 1 (IGF1) levels of age-matched controls. GH treatment is known to increase IGF1 levels, leading to the abnormal growth of adenoids and tonsils.
Data on height, weight, body mass index (BMI, a measure of body fat) and IGF1 were determined for each patient. Polysomnography (PSG), a test used to diagnose sleep disorders, evaluated sleep parameters, oxygen blood levels, breathing, and leg movements. Data was collected at baseline, or study start, and every six months. No differences were seen between the two patient groups at baseline.
All enrolled were considered overweight, with a BMI of 27.1 kilograms per square meters (a normal range is 18.5 to 24.9), and had low IGF1 levels.
Sleep efficiency, a measure of sleep quality, was determined by dividing the total sleep time by the total time in bed, multiplied by 100. A finding between 85% and 90% is considered normal, while above 90% or above is considered good, quality sleep. A sleep efficiency of 89% was the baseline measure for patients in the study.
The apnea-hypopnea index (AHI) was used as an indicator of the severity of sleep apnea. AHI represents the number of apnea and hypopnea (a drop in airflow for at least 10 seconds) events during each hour of sleep. No evidence of sleep apnea was found in 34 patients, while the remaining three had mild apnea.
One year of GH use increased IGF1 levels in treated patients, which remained unchanged in those on placebo. No significant differences were found between these patient groups in measures of respiration or sleep quality.
Measures taken at the end of three years, which included the two years of open-label GH treatment, showed levels of IGF1 rose from 104 micrograms (mcg)/L at baseline to 178 mcg/L. Sleep efficiency increased to a median of 91%.
However, the length of the longest apnea, measured at a last patient visit, significantly increased after three years of continuous GH use. AHI, which measures apnea severity, inconsistently rose during the study, as did the number of oxygen desaturations, or drops in oxygen levels in the blood.
“The clinical relevance of these findings is uncertain,” the researchers wrote.
Sleep quality “improved, but on the other hand the length of the longest apnea and the number of desaturations inconsistently increased,” they noted.
No changes were observed in any of the other measures.
SRBDs, while common in adults with PWS, were not evident among patients in this study, the researchers noted. They suggested that one explanation for this could be that enrolled patients, while overweight, were not as excessively overweight as in previous research.
The development of sleep apnea has been associated with sudden death in children with PWS on GH treatment. In this study, adult patients were treated with lower GH doses, and no deaths were reported.
Sleep efficiency “improved during GH treatment and no clinical, significantly negative, impact on respiration was seen,” the researchers wrote.
“The etiology [cause] of breathing disorders is multifactorial and awareness of them should always be present in adults with PWS with or without GH treatment,” they added.
Two study limitations were its small number of participants and the lack of a control group after its first year.