Growth Hormone Secretagogues

Because the aging-related decline in GH secretion results from changes upstream of the pituitary, hormonal replacement can theoretically be achieved with GHRH or growth-hormone- releasing peptides (GHRPs). There are several conceptual advantages of these therapies over exogenous GH itself [32]. First, even when administered continuously, they preserve the physiological pulsatility of GH release, presumably mediated via intermittent endogenous somatostatin secretion. In addition, the normal negative feedback regulation by IGF-I upon GH release confers relative protection against overtreatment with these agents.

The only GH secretagogue presently approved for use as replacement therapy is GHRH (1–29) NH₂ (Geref, Serono), which has been licensed to treat childhood GHD but is being tested in adults as well. Various GHRPs and nonpeptide GHRP mimetics are also under investigation in elderly subjects [32]. Only shortterm trials have been published to date, sufficient to assess only hormonal effects. IGF-I has been raised to youthful levels in older individuals with once- or twice- daily subcutaneous injections of GHRH as well as with infusions or daily oral preparations of GHRPs.Data on body composition and functional end points are being compiled. Side effects resulting from inadvertent overtreatment with secretagogues should be less common than with exogenous GH because of the moderating effects of feedback regulation; studies to date have generally found this to be true. However, some patients do report typical GH-related symptoms of fluid retention as well as allergic reactions at injection sites. Current GH secretagogue formulations delivered transnasally and orally are limited and quite short-acting and therefore are unpredictable. For these compounds to become clinically useful, development of more potent preparations, adjuvants to enhance potency, or synergistic GHRH-GHRP combinations is necessary.