Twice-daily injections of the growth hormone-releasing peptide GHRH(1-29) increased growth velocity from 4.8 to 7.2 cm/year in short children without growth hormone deficiency, but growth returned to baseline after stopping treatment.
4.8→7.2 cm/yeargrowth velocity increased 50% during 12 months of GHRH peptide treatment in short children without growth hormone deficiency
What the researchers found
After 12 months of twice-daily subcutaneous GHRH(1-29)NH2 injections (20 μg/kg):
- Mean height velocity increased from 4.8 cm/year to 7.2 cm/year (p=0.001) — a 50% improvement
- Children who were growing slowest before treatment showed the most dramatic improvement, with some reaching normal growth velocity percentiles
- Final height prediction increased by a mean of 3.4 cm (SD 2.6)
- IGF-1 levels increased during treatment, as did fasting blood glucose and insulin
- Overnight GH levels and GH responses to GHRH testing paradoxically fell during the 12 months of therapy
- After stopping treatment, catch-down growth occurred in the first 3 months (HV 3.89 cm/year), though growth velocity returned to pre-treatment baseline by 6–12 months off therapy
Why it matters
Idiopathic short stature — being significantly short without any identifiable hormone deficiency — is a common pediatric concern with limited treatment options. This study showed that stimulating the body's own growth hormone system with a GHRH peptide could accelerate growth, offering a potentially more physiological approach than injecting growth hormone directly. However, the catch-down growth after stopping raises questions about long-term benefit.
How the study worked
Eighteen short pre-pubertal children (ages 4.3–11.0, 17 male) with idiopathic short stature and normal GH levels were treated with twice-daily subcutaneous GHRH(1-29)NH2 at 20 μg/kg for 12 months. Height was measured every 3 months. Overnight GH profiles and GHRH stimulation tests were performed at 0, 3, 6, and 12 months. Growth was also monitored for 12 months after stopping treatment. One patient was withdrawn for non-compliance.
What this study cannot tell us
Small sample with only 18 children (17 male, 1 female), making it impossible to assess sex differences. No control group receiving placebo — growth was compared to pre-treatment rates. The catch-down growth after stopping suggests no permanent height gain may occur. Increased fasting glucose and insulin during treatment raises metabolic safety concerns for longer use. The study predates modern growth standards and statistical methods.
How to read the evidence
This is a small, uncontrolled clinical trial with 18 patients and no placebo group. While it provides direct human evidence of GHRH's growth-promoting effects, the lack of randomization and controls limits the strength of causal conclusions.
When this study was published
Published in 1994, this is a historical study from the early era of GHRH peptide research. The specific GHRH(1-29) peptide (sermorelin) was later FDA-approved but has since been discontinued. The growth physiology insights remain relevant.
The bigger picture
This 1994 study explored an era when researchers hoped GHRH peptides could replace growth hormone injections for some conditions. The approach of stimulating endogenous GH release rather than replacing it directly has influenced the development of later growth hormone secretagogues like ipamorelin and tesamorelin. The finding that growth benefits didn't persist after stopping treatment remains relevant to debates about peptide-based growth therapies today.
Questions still open
- Would longer treatment duration with GHRH produce permanent gains in final adult height?
- Do the increases in fasting glucose and insulin during GHRH treatment pose long-term metabolic risks in children?
- How does this GHRH peptide approach compare to direct growth hormone replacement for idiopathic short stature?
Common questions
What is GHRH(1-29) and how does it differ from growth hormone?
Why did growth slow down after stopping the GHRH injections?
Read the original research
Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity.
Clinical endocrinology, 41(4), 487-93
Citation
Kirk, J M; Trainer, P J; Majrowski, W H; Murphy, J; Savage, M O; Besser, G M. (1994). Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity.. Clinical endocrinology, 41(4), 487-93.