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Growth Hormone Status during Long-Term Hexarelin Therapy

cvictorg

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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.

The therapeutic use of GHRH has been limited by desensitization occurring after long-term administration and resulting in a progressively reduced GH response. This has been clearly demonstrated in rats (5) and man (6). The mode of administration and poor bioavailability of GHRH further hinders its use. The recent use of a GHRH analogue, administered sc to normal elderly subjects, however, suggested more favorable results with no attenuation of the GH response to the GHRH analogue after 16 weeks of administration (7). Khorram et al. (7) also demonstrated an increase in serum IGF-I, IGFBP-3, and GH binding protein over the 16-week study. Furthermore, this group went on to demonstrate significant changes in biological endpoints, with an increase in skin-fold thickness in both male and female subjects, and an increase in lean body mass, insulin sensitivity, general well-being, and libido in the male subjects. The increase in endogenous GH, as a result of GHRH analogue administration in elderly subjects, may therefore be beneficial. The route of administration of the GHRH analogue, however, remains a disadvantage and may affect com-pliance.

Hexarelin is capable of causing GH release in normal subjects after oral administration (1, 8). The availability of a powerful orally active GH secretagogue with an ability to cause pulsatile GH release, has obvious advantages over administration of sc GH and GHRH analogues. The potential therapeutic use of hexarelin and similar agents, however, will be determined, in part, by their GH releasing capacity after chronic administration. In the present study, we have demonstrated that 16 weeks of twice-daily sc hexarelin therapy results in an attenuated GH response to hexarelin, as evidenced by a decrease in both peak GH response and AUCGH. Importantly, however, this reduction in hexarelin-stimulated GH release was partial, with all but one subject still releasing GH after 16 weeks of therapy.

Growth Hormone Status during Long-Term Hexarelin Therapy -- Rahim et al. 83 (5): 1644 -- Journal of Clinical Endocrinology & Metabolism
 

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