Sustained‐release Recombinant Human Growth Hormone Improves Body Composition and Quality of Life in Adults With Somatopause

To the Editor: A progressive decline in growth hormone (GH) secretion parallels normal aging.1 Therefore, most adults past middle age are confronted with somatopause, a condition of physiological GH deficiency. A reduction in GH secretion causes central fat accumulation, sarcopenia, dyslipidemia, greater cardiovascular mortality, and poorer quality of life (QoL).2 For these older adults, a number of clinical trials of GH replacement therapy have demonstrated beneficial effects of the therapy on lipid profile, body fat distribution, bone metabolism, and well-being.3,4 Nevertheless, several concerns remain regarding diabetes mellitus (DM), peripheral edema, and arthralgias.4 A technical difficulty of GH administration is also an important concern for older adults. A formulation of sustained-release recombinant human GH (SR-rhGH; Declage, LG Life Sciences, Ltd., Seoul, Korea) using sodium hyaluronate microparticles was developed that can be administered weekly.5 In the current study, a low dose of SR-rhGH was administered for 26 weeks to subjects with somatopause, and the safety and the effects of the formulation on body composition and QoL were investigated. Healthy adults aged 50 and older with serum insulin-like growth factor (IGF)-1 levels less than 150 ng/mL were eligible for this study. After a 4-week screening period, participants subcutaneously received 6 IU (2 mg) of SR-rhGH weekly for 26 weeks. At every visit, vital signs, height, weight, and waist circumference (WC) were checked. Serum IGF-1 was measured using a commercially available standard Immunotech IRMA kit, according to the manufacturer's protocols (Immunotech, Beckman Coulter, Inc., Marseilles, France); manufacturer's reference range 107–310 ng/mL). Measurements of fat mass (FM) and lean body mass (LBM) were obtained using whole-body dual X-ray absorptiometry (QDR 4500A, Hologic Inc., Bedford, MA). Computed tomography (CT) scans (SOMATOM Sensation 64, Siemens, Forscheim, Germany) were used to estimate levels of visceral, subcutaneous, and total adipose tissues (VAT, SAT, and TAT, respectively). QoL was assessed using the Quality of Life-Assessment of Growth Hormone Deficiency in Adults questionnaire.6 Caloric intake was assessed according to daily self-recording of episodes by participants in a nutrition diary. Adherence was calculated as the percentage of the number of injections out of the number scheduled. Statistical analyses were performed using SPSS, version 16.0 (SPSS, Inc., Chicago, IL). Thirty-three participants (24 female; mean age 64.0 ± 7.6) were analyzed. The mean baseline IGF-1 level of 123.4 ng/mL increased to 174.8 ng/mL at Week 4, and the level was maintained for the remaining testing period. At Week 26, average LBM was 0.45 kg greater, WC was 1.06 cm lower, and QoL was significantly better (Table 1). Serum levels of biochemical markers of bone resorption and formation also increased. There was no significant change in body fat distribution or FM. Although there was no change in fasting blood glucose, glycosylated hemoglobin and serum insulin levels increased significantly (0.30% and 2.91 μIU/mL, respectively). Calculated homeostatic model assessment of insulin resistance increased 0.92. Adverse events included pruritus (10.5%), arthralgia (5.3%), and edema (5.3%), but their symptoms were well tolerated. Returned vial counts suggested excellent adherence, with 99.7% of the vials injected into participants. The current study examined the efficacy and safety of SR-rhGH treatment in healthy middle-aged and older adults for the first time and showed that SR-rhGH has comparable efficacy in terms of elevation in IGF-1 levels, greater LBM, lower WC, and better QoL.3,7 Using CT scans for body fat analysis, no significant changes were observed in VAT, SAT, or TAT. A concurrent exercise intervention might have led to better responses to SR-rhGH. Furthermore, a previous report showed dose-dependent changes in body composition.8 Participants in the current study had low baseline body mass index, and a lower dose of SR-rhGH was provided than in previous trials, which might have contributed to insignificant effects on body composition. The SR-rhGH treatment for 26 weeks significantly increased the serum levels of biochemical markers of bone resorption and formation. A previous study confirmed simultaneous increases in bone resorption and formation, and increases in bone formation markers were significantly greater than those in bone resorption markers only after 6 months,9 suggesting a possibility of a delayed increase in bone density after prolonged GH supplement. In general, the proportions of adverse events were not significantly greater in participants who administered once-weekly injection of SR-rhGH than in those receiving daily injection of rhGH.4 In summary, this study suggests that 26-week SR-rhGH replacement therapy can restore body composition and QoL in part in adults with somatopause. The once-weekly regimen of SR-rhGH was well tolerated without significant adverse effects. Further placebo-controlled studies examining long-term effects will be invaluable in characterizing the efficacy of SR-rhGH on sarcopenia in older adults. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This study was supported by a grant from the Korea Healthcare Technology R&D Project run by the Ministry for Health, Welfare and Family Affairs of the Republic of Korea (No. A085136). Author Contributions: JKP analyzed and interpreted the data and wrote the draft. EJL, YSC, and Sung Woon Kim designed the study, collected the data, recruited and looked after subjects, and reviewed the draft. JWH, COK, and Sang Woo Kim interpreted the data and reviewed the manuscript. CYL performed all statistical analyses. All authors also made intellectual contribution to the study and approved the final manuscript. Sponsor's Role: The sponsor had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and had the final responsibility for the decision to submit for publication.