Growth Hormone Treatment May Improve Sleep Efficiency in Prader-Willi Syndrome

The rare, genetic, multisymptom, neurodevelopmental disease Prader-Willi syndrome (PWS) is typified by muscular hypotonia, hyperphagia, obesity, behavioral problems, cognitive disabilities, and endocrine deficiencies, one of which is growth hormone (GH) deficiency. Sleep is also adversely affected by the rare condition.

Knowing the positive results seen from GH therapy on body composition, physical capacity, and quality of life—and highlighting that PWS is characterized by abnormal body composition—the authors of a recent study theorized that the treatment might also have beneficial effects on the sleep deficiencies associated with PWS, chiefly sleep apnea and abnormal sleep patterns. Their findings were published in The Journal of Clinical Endocrinology & Metabolism.

Their double-blind, randomized, placebo-controlled study was for 1 year, after which all of the patients enrolled received 2 years of treatment with GH. Initially, the 22 women and 15 men were randomized 1:1 to treatment for 1 year with either GH (n = 19) or placebo (n = 18) and had polysomnographic measurements taken every 6 months. Considering the additional 2 years of GH therapy, the authors also used a mixed-effect regression model for comparison among only those who received GH for 3 years.

“There is limited information on sleep-related breathing disorders in adults with PWS and especially in relation to GH treatment,” the authors wrote. “The aims of this study were to evaluate the effect of short- and long-term GH treatment on respiratory and sleep parameters

At baseline, the study participants had a median age of 29.5 (range, 16.0-41.6) years and classified as overweight, with a median body mass index of 27.0 (range, 17.9-41.9) kg/m² for the placebo group and 27.3 (19.9-44.8) kg/m² for the GH group. Median insulin-like growth factor 1 (IGF-1) levels were low, at 115 (range, 61.0-185.0) mcg/L; sleep efficiency (SE) for both groups was 89.0% (range, 41.0%-99.0%); and the median apnea hypopnea index (AHI) was 1.4 (range, 0.0-13.9).

By the 1-year mark, the following changes were noted:

• IGF-1 jumped to 165 (range, 69-257) mcg/L for the GH group while remaining level for the placebo group (P = .013).
• Respiration and sleep parameters (AHI, longest apnea, periodic limb movement, oxygen saturation, IGF-1 level, total desaturations, REM sleep and latency, SE, delta sleep) did not differ between the groups.

After the extended 2-year period of GH treatment for all, these were the findings:

• Among those who received GH for 3 years (main study + 2-year extension), IGF-1 levels rose from 104 mcg/L at baseline to 178 mcg/L, or a 71% increase.
• SE rose from a median 86.7% (range, 58.5%-99.9%) to 91.0% (range, 57.0%-100.0%).
• AHI trended upward to 2.4, from 2.0, but was deemed an intermittent significant association with baseline.
• Desaturations inconsistently rose, despite adjusting for body mass index.

The study treatment consisted of either GH or placebo, 0.3 or 0.4 mg/day if body weight was below or above 100 kg, for the first 4 study weeks; a dosage increase to 0.6 or 0.8 mg/day, respectively, for those below or above 100 kg, and maintaining that for the following 11 months; and for the 2-year period, titrating the GH dose according to IGF-1 levels of age-matched controls.

Overall, SE steadily increased from the 6-month mark for those who received continuous GH treatment for 3 years, but the other parameters did not change, the authors said, and significant differences were not seen on any respiration or sleep parameters for initial the 1-year trial period.

Noting that respiratory disease can be a frequent, sometimes sudden, cause of death among those with PWS, the authors noted that all adults with the disease can benefit from treatment with GH, proposing that “GH treatment increases muscle strength, which would lead to less interrupted sleep and an increase in SE,” and the therapy can be safely initiated in children. Both groups also would need regular sleep analysis.

“GH treatment of adults with PWS has many positive effects, and our study showed that GH treatment is safe and concerns of a negative impact on sleep-related parameters could not be confirmed,” they concluded. “While further studies in this context are warranted, our results add to the confidence in GH treatment in adults with PWS.”

Reference

Shukur HH, Hussain-Alkhateeb L, FArholt T, Nørregaard O, Jøgensen AP, Hoybye C. Effects of growth hormone treatment on sleep-related parameters in adults with Prader-Willi syndrome. J Clin Endocrinol Metab. 2021;106(9):e3634-e3643. doi:10.1210/clinem/dgab300