GHRH (1-29) dosing & administration

Prakash A, Goa KL · 1999

Sermorelin is the shortest synthetic fragment of growth hormone-releasing hormone with full activity. A single intravenous 1 mcg/kg dose is a rapid and relatively specific test for growth hormone deficiency, producing fewer false positives in children without deficiency than other provocative tests — though a normal response cannot rule out a hypothalamic cause, so it is used alongside conventional testing rather than instead of it. For treatment, the review calls the data limited: once-daily subcutaneous 30 mcg/kg at bedtime raised height velocity over 12 months in some prepubertal children with idiopathic deficiency, with a few children followed to 36 months, and the effect on final adult height was never determined. Height-velocity gains were SMALLER than those in children given somatropin at the same 30 mcg/kg per day. Across that programme — 350 patients exposed to sermorelin in clinical trials — transient facial flushing and injection-site pain were the most commonly reported adverse events.

Wilton P, et al · 1993

In a study of 30 healthy men, even tiny intravenous doses of just 0.25 micrograms per kilogram of body weight produced significant growth hormone release. The maximum growth hormone response occurred at doses of 1-2 micrograms per kilogram, with peak growth hormone levels reaching approximately 90 milli-international units per liter. Growth hormone levels remained elevated for about 3 hours even though the peptide itself was rapidly eliminated from the body. Intranasal delivery had poor bioavailability of only 3-5%, but higher intranasal doses of 50 micrograms per kilogram were as effective as just 1 microgram per kilogram given intravenously. Importantly, repeated intranasal dosing did not suppress the body's natural nighttime growth hormone secretion.

Achermann JC, et al · 2000

Testing with low-dose GHRH(1-29) revealed that patients with growth hormone deficiency caused by radiation therapy showed a reduced growth hormone response compared to healthy individuals. This demonstrated that GHRH(1-29) is a useful diagnostic tool for identifying and characterizing different types of growth hormone deficiency.

Achermann JC, et al · 1999

Studies using continuous GHRH(1-29) infusions revealed how growth hormone pulses are actually generated in the body. The research showed that growth hormone pulses are created by the intermittent withdrawal of somatostatin (an inhibitory hormone), while GHRH(1-29) provides a permissive background signal that allows growth hormone secretion to occur. This mechanism explains why GHRH(1-29) is so effective at stimulating natural growth hormone release.

Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Eengrand P, Shah S · 1996

The trial the approved dose comes from. 110 previously untreated prepubertal growth hormone-deficient children received 30 mcg/kg per day of GHRH(1-29) subcutaneously at bedtime for up to a year in a multicentre open-label study; 86 were eligible for the efficacy analysis. Mean height velocity rose from 4.1 ± 0.9 cm/year at baseline to 8.0 ± 1.5 cm/year at 6 months and 7.2 ± 1.3 cm/year at 12 months, and 74% of the children were judged good responders at 6 months. Bone age advanced in step with height age (ratio 1.04 ± 0.58, p=0.63), fasting glucose did not change, and there was no excessive IGF-I generation. Open-label: there was no placebo arm.

Ogilvy-Stuart AL, Stirling HF, Kelnar CJ, Savage MO, Dunger DB, Buckler JM, Shalet SM · 1997

Nine prepubertal children with growth hormone deficiency caused by cranial or craniospinal irradiation received GHRH(1-29)-NH2 15 mcg/kg TWICE daily by subcutaneous injection for a year — a divided dose, 30 mcg/kg across the day. Height velocity rose from 3.3 cm/year before treatment to 6.0 cm/year (p=0.004). In the following year on growth hormone itself the same children grew 7.5 cm/year, so GHRH worked but worked less well than GH. In that cohort (n=9), with no control arm and no placebo, no adverse events attributable to GHRH and no adverse changes in clinical chemistry, haematology, lipids or thyroid function were recorded over the treatment year — a cohort far too small to detect anything uncommon.

Khorram O, Laughlin GA, Yen SS · 1997

The adult trial — and it tested a different molecule. Ten women and nine men aged 55 to 71 self-injected saline nightly for 4 weeks, then [Nle27]GHRH-(1-29)-NH2 (a norleucine-27 analogue, not sermorelin) at 10 mcg/kg nightly for 16 weeks, single-blind and placebo-controlled. Nocturnal GH rose in both sexes (women p<0.01, men p<0.05) and IGF-I rose within 2 weeks (p<0.05) but drifted back toward baseline by 16 weeks. Skin thickness increased in both sexes (p<0.05). Lean body mass increased in MEN ONLY (p<0.05), with no other change in body composition and no change in bone mineral density in either sex — body fat did not fall. Insulin sensitivity, general well-being (p<0.05) and libido (p<0.01) improved in men only. Sleep quality was unaffected. The only adverse effect was transient hyperlipidaemia, resolved by the end of the study. Nineteen people.

Khorram O, Yeung M, Vu L, Yen SS · 1997

The same 19 people and the same norleucine-27 analogue at 10 mcg/kg nightly for 16 weeks. Twelve-hour integrated GH rose 107% in men and 70% in women, and IGF-I rose 28%. B cells rose 30% by 16 weeks with a 50% increase in responsiveness to B-cell mitogens, lymphocytes expressing the IL-2 receptor rose 70%, and T-cell responsiveness to phytohaemagglutinin rose 50%. Total T cells, T-cell subsets and natural killer cells did not change. The authors report no adverse effects. Again: 19 people, an analogue rather than sermorelin, and immune cell counts rather than any clinical outcome such as infection rate.