Growth Hormone Secretagogues: Charting Their Clinical Potential in 2000

Growth hormone (GH) is a critical endocrine hormone regulating somatic growth, metabolism, and body composition throughout life. While recombinant GH therapy was established for treating GH deficiency, its administration often lacked the physiological pulsatility of natural GH secretion and could have side effects. This comprehensive review from the year 2000 aimed to consolidate the burgeoning understanding of growth hormone secretagogues (GHSs) and critically evaluate their emerging clinical potential as a more physiological alternative.

The review elucidated that GHSs, including ghrelin mimetics like MK-0677 (ibutamoren) and GHRP-6, effectively stimulate the GH secretagogue receptor (GHSR), leading to a robust, pulsatile release of GH from the pituitary gland. This action was noted to mimic the body's natural GH secretion patterns more closely than direct exogenous GH administration. Early studies cited within the review consistently demonstrated that GHS administration could achieve significant increases in circulating GH levels, often showing 2-fold to 5-fold elevations in peak GH concentrations compared to placebo controls. The most pivotal finding was the confirmation that GHSs represent a novel and highly promising therapeutic class capable of stimulating the body's own GH production, thereby offering a potentially safer and more physiological approach to modulate GH levels than direct GH replacement. The authors highlighted promising therapeutic applications in conditions such as adult GH deficiency, catabolic states (e.g., in elderly or chronic illness), and potentially osteoporosis, where GHSs showed potential to improve lean body mass, bone mineral density, and overall metabolic profiles.