Growth Hormone Use Beyond Childhood Aids Young Adults With PWS, Study Finds

Growth hormone treatment given for years in childhood and then either restarted or continued as patients reach adult height shows sustained positive effects on body composition among young adults with Prader-Willi syndrome (PWS), including a decrease in fat mass, according to a Dutch study.

The study, “Three years of growth hormone treatment in young adults with Prader-Willi syndrome: sustained positive effects on body composition,” was published in the Orphanet Journal of Rare Diseases.

Growth hormone (GH) deficiency is a common feature of PWS and can result in a short stature from the second decade of life. GH therapy is recommended for PWS patients as a means to improve stature, metabolism, and ease cognitive difficulties, as well as to control the weight gain that is also common in this population.

People with PWS often develop an insatiable appetite, which leads to overeating and obesity.

Multiple studies support the benefit of childhood GH treatment in PWS, but most have only tracked patients for one year, and often include people not treated during childhood or whose childhood treatment went unreported.

One study evaluated the effects of GH therapy over a two-year time course in adults. Positive effects on fat mass and lean body mass were reported in adults, but effects in children were not analyzed.

Most PWS children also stop GH treatment after attaining adult height, because the therapy is typically not approved for reimbursement from that point on, the scientists wrote.

To obtain a better picture of the benefits of long-term GH treatment, researchers in the Netherlands examined the outcomes of 43 young adults (age at study start, 16 to 20) from the Dutch Young Adult PWS (YAP) study — EudraCT number 2011-001313-14.

All patients had all received at least five years of GH therapy as children, and at least three years of continuous GH therapy after attaining their adult height.

Study participants had taken part in one of two previous studies. Patients from the Dutch PWS Cohort study received continuous GH therapy, but at lower doses of GH (0.33 mg/m²/day, down from 1 mg/m²/day) after reaching adult height. Those from the Transition Study had a median one-year gap in GH treatment, before being restarted at the same lower dose as the other patients. All reached adult height in their mid- or late teenage years.

Data were collected after all patients had used a stable lower dose for one year, to control for any effects that a sharp change in dosage might have.

Over a three year follow-up period, patients’ mean percentage of fat mass decreased, while their lean body mass — the difference between total body weight and body fat weight — remained stable.

Behind these overall results, some variation existed between the groups that received continuous treatment, and those with a gap in therapy.

Patients who restarted GH after a one-year discontinuation saw a decrease in fat mass and an increase in lean body mass during the first year of restarting treatment. This suggests that restarting GH therapy can recover the positive effects on body composition that are lost during a year of GH discontinuation, the investigators said.

Mean body fat mass of patients in the continuously treated group increased over six months following dose lowering and then stabilized. In turn, lean body mass in this group decreased slightly over six months but without statistical difference, after which it, too, stabilized.

Both the levels of Insulin-like growth factor-I — whose levels are assessed to monitor the effectiveness of GH treatment — and patients’ body-mass index (BMI) remained stable over the course of the study.

Because body composition changed in response to treatment while BMI did not, the scientists suggested that body composition may serve as a more informative metric than BMI in PWS studies.

Patients tolerated the continuous GH treatment well throughout the three year period, with no serious adverse events deemed related to GH.

Mean fasting glucose (blood sugar) and insulin levels also remained stable. Blood pressure did not change significantly. No participant developed type 2 diabetes.

“Three years of growth hormone treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term growth hormone treatment,” the researchers wrote.

“Furthermore,” they added, “it shows that restart of GH after 1 year of discontinuation is able to restore the deteriorated body composition.”