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Growth Hormone Status during Long-Term Hexarelin Therapy

Department of Endocrinology (A.R., S.M.S.), Christie Hospital, Withington, Manchester, M20 4BX; and University Department of Geriatric Medicine (P.A.O.), South Manchester University Hospital Trust, Manchester, M20 8LR, United Kingdom

Address all correspondence and requests for reprints to: Professor S. M. Shalet, Department of Endocrinology, Christie Hospital National Health Service Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.

Hexarelin, a powerful GH-releasing peptide, is capable of causing profound GH release in normal subjects after oral, intranasal, iv, and sc 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 sc hexarelin therapy (1.5 µg/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 (AUC_GH) at weeks 0, 1, 4, 16, and 20 were 19.1 ± 2.4 µg/L·h, 13.1 ± 2.3 µg/L·h, 12.3 ± 2.4 µg/L·h, 10.5 ± 1.8 µg/L·h, and 19.4 ± 3.7 µg/L·h, respectively. There was a significant change in AUC_GH over the study period (P = 0.0003). Further analysis showed that, compared with baseline, the decrease in AUC_GH at week 4 and week 16 were significant (P < 0.05 and P < 0.01, respectively). Four weeks after completion of hexarelin therapy, the AUC_GH increased significantly, compared with AUC_GH 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.

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