Hexarelin makes the body release a lot of growth hormone at first, but if you keep injecting it twice a day for weeks, the hormone boost gets smaller. In a 16‑week study with older adults, the boost fell by about half, but after stopping the drug for four weeks the hormone response bounced back to the original level. This means the body gets used to hexarelin, but the tolerance can be undone with a short break.

Hexarelin, a potent growth hormone (GH)-releasing peptide, is capable of causing profound GH release in normal individuals. If the GH response to hexarelin in humans becomes appreciably attenuated following long-term administration, this would seriously limit the potential therapeutic use of hexarelin and similar agents. The effect of twice-daily subcutaneous injections of hexarelin on GH release was therefore investigated over a period of 16 weeks in 12 healthy elderly individuals. The mean (+/- SEM) areas under the GH curve (AUCGH) at weeks 0, 1, 4 and 16 were 19.1 +/- 2.4, 13.1 +/- 2.3, 12.3 +/- 2.4 and 10.5 +/- 1.8 microg/l/hour, respectively. There was a significant change in AUCGH over the study period (P = 0.0003). Further analysis showed that the decreases in AUCGH at weeks 4 and 16 were significant (P < 0.05 and P < 0.01, respectively) compared with baseline values. Four weeks after completion of the 16-week study period, hexarelin was again administered. On this occasion, AUCGH increased significantly compared with that at week 16 (from 10.5 +/- 1.8 to 19.4 +/- 3.7 microg/l/hour; P < 0.05) and was not significantly different compared with that at week 0. These results show that attenuation of the GH response after long-term hexarelin therapy is partial and reversible.