A 16‑week study of twice‑daily hexarelin shots showed that the body’s GH surge gets smaller over time, but overall IGF‑1 levels, muscle, fat, and bone density stay about the same. After stopping the drug, the GH response comes back to normal.

Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, i.v., and s.c. administration. The effect of long-term administration on GH levels in adults is unknown. We have, therefore, assessed the effects of 16 weeks of twice-daily s.c. hexarelin therapy (1.5 micrograms/kg BW) on the GH response to a single injection of hexarelin, and also the GH response to hexarelin 4 weeks after cessation of hexarelin therapy. We have also assessed the effects of chronic hexarelin therapy on serum insulin-like growth factor (IGF)-I, IGF binding protein-3, markers of bone formation (osteocalcin, procollagen-type-III-N-terminal-peptide, and C-terminal propeptide of type I collagen), and resorption (urinary deoxypyridinoline and pyridinoline), body composition, and bone mineral density. The mean (+/- SEM) area under the GH curve (AUCGH) at weeks 0, 1, 4, 16, and 20 were 19.1 +/- 2.4 micrograms/L.h, 13.1 +/- 2.3 micrograms/L.h, 12.3 +/- 2.4 micrograms/L.h, 10.5 +/- 1.8 micrograms/L.h, and 19.4 +/- 3.7 micrograms/L.h, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUCGH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUCGH increased significantly, compared with AUCGH at week 16 (P < 0.05), and was not significantly different from that at week 0. Serum IGF-I and IGF binding protein-3 did not change significantly over the 20-week period (P = 0.24 and P = 0.74, respectively). Of the bone markers measured, only serum C-terminal propeptide of type I collagen changed significantly and was higher at week 16, compared with baseline (P = 0.019). Total body fat, lean body mass, and bone mineral density had not changed significantly at week 16, compared with baseline (P = 0.6, P = 0.3, and P = 0.3, respectively). In summary, we have demonstrated that chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin. In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal. The therapeutic potential of chronic hexarelin requires further investigation.