Growth Hormone Side Effects: What Studies Report

Growth hormone (GH) has one of the longer safety records in endocrinology, because recombinant human GH has been studied in children and adults for decades and tracked in large international registries. The published record that addresses adverse events comes overwhelmingly from approved, physician-supervised products used for recognised indications — growth hormone deficiency (GHD), idiopathic short stature, Noonan syndrome and selected adult conditions — plus separate reviews describing non-medical use in sport. This page summarises what those papers reported. This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question or treatment decision.

Where the safety evidence comes from

Four kinds of publication dominate. First, prospective registries: an analysis of the full KIGS cohort reported on the safety and efficacy of pediatric growth hormone therapy across a very large international group of treated children, making it one of the broadest sources of adverse-event data in the field (PMID 36102184). Second, randomised phase 3 trials, which compared newer long-acting products against daily somatropin and recorded adverse events in each arm — for example the heiGHt trial of weekly lonapegsomatropin in treatment-naïve children with GHD (PMID 34272849) and the phase 3 comparison of weekly somatrogon with daily somatropin (PMID 35405011).

Third, pooled evidence: a systematic literature review and network meta-analysis compared long-acting growth hormone products with daily GH in children with GHD and reported on both efficacy and safety outcomes (PMID 38580693), and a separate systematic review and meta-analysis examined efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting versus daily GH (PMID 37236413). Fourth, post-marketing surveillance: a review of pharmacovigilance in children described how adverse drug reactions in pediatric populations were identified, reported and interpreted, including the limitations of spontaneous reporting systems (PMID 22748689).

Growth Hormone Side Effects: What Studies Report

Injection-site and local tolerability findings

Local reactions were among the most consistently tabulated events in modern trials. The phase 3 study comparing once-weekly somatrogon with daily somatropin in children with GHD reported injection-site pain more frequently in the weekly arm than in the daily arm, while overall adverse-event rates were otherwise broadly comparable (PMID 35405011). In the heiGHt trial, researchers reported that weekly lonapegsomatropin was generally well tolerated with an adverse-event profile similar to daily somatropin over the treatment period (PMID 34272849). A large, prospective, real-world study of long-term pegylated GH in children with GHD also recorded injection-site findings among treatment-emergent events during multi-year follow-up (PMID 36669772).

When these trials were pooled, the network meta-analysis reported that long-acting and daily GH formulations had broadly comparable safety profiles in children with GHD, with differences concentrated in administration-related rather than systemic events (PMID 38580693). The parallel systematic review reached similar conclusions on safety while also reporting adherence and quality-of-life differences between weekly and daily regimens (PMID 37236413).

Metabolic and laboratory findings: What Studies Report

Because GH acts partly through IGF-1 and influences insulin sensitivity, trials and registries routinely reported laboratory surveillance rather than symptoms alone. The long-term prospective study of pegylated GH in children with GHD reported that IGF-1 levels, thyroid function and glucose-related parameters were monitored throughout follow-up as part of the safety assessment (PMID 36669772). A 2025 review of GH treatment in children with idiopathic short stature reported on efficacy, safety and longer-term outcomes in that indication, where treatment is given to children who are not GH-deficient and where the benefit–risk discussion has been most debated (PMID 40848513).

In adults, the randomised phase 3 trial of once-weekly somapacitan reported that treatment was effective and well tolerated in adults with GH deficiency, with adverse events described as generally mild to moderate and comparable to daily GH (PMID 32022863). Adult and pediatric safety data are not interchangeable: the underlying diagnoses, treatment goals and monitoring intervals differ, and the study populations were selected and supervised accordingly (PMID 32022863).

Long-term and rare events: What Studies Report

Rare outcomes are the hardest to study, which is why registries matter. The full KIGS cohort analysis reported adverse events, including serious events, across a large pediatric population treated with GH and concluded that the observed safety profile was consistent with previous reports from the same programme (PMID 36102184). The review of pediatric pharmacovigilance explained why such long-running databases complement spontaneous reporting, since under-reporting and off-label prescribing can obscure rare paediatric signals (PMID 22748689).

Duration of observation is the limiting factor for the newest products. Researchers reported that long-acting GH trials were typically measured in months to a few years, which the network meta-analysis identified as a constraint on conclusions about long-term safety relative to decades of daily somatropin experience (PMID 38580693). The multi-year real-world pegylated GH study was published partly to extend that observation window in routine practice (PMID 36669772).

Condition-specific safety questions: What Studies Report

Adverse-event expectations differ by diagnosis. A review of growth and growth hormone treatment in Noonan syndrome discussed the use of GH in that population and the additional monitoring considerations raised by the underlying genetic condition, including cardiac and tumour-surveillance questions (PMID 31115197). In adults with a neuromuscular disorder, a 2025 study of testosterone and recombinant human growth hormone in facioscapulohumeral muscular dystrophy reported on outcomes and adverse events in that specific trial population (PMID 40900971). Findings from one indication were not presented by the authors as generalisable to others.

Non-medical and doping contexts: What Studies Report

A separate strand of literature deals with GH used outside medical indications. A 2023 review of doping and sports endocrinology described growth hormone, IGF-1, insulin and erythropoietin as substances used for performance purposes and discussed the detection methods and health risks associated with that use (PMID 36736729). That review addressed supraphysiological exposure in people without a deficiency, which the authors treated as a different risk scenario from replacement therapy in diagnosed GH deficiency (PMID 36736729). Research-grade or unapproved GH and GH-secretagogue materials sold for laboratory use are not the products studied in any of the trials above, and no cited paper evaluated them.

Weekly versus daily administration: what the comparative studies reported

Much of the recent safety literature exists because weekly formulations had to be compared against the daily standard. The table below summarises the comparative and registry sources cited on this page.

How adverse events were counted — and why numbers differ between papers

Comparing adverse-event rates across GH publications is harder than it looks, and several of the cited papers said so directly.

• Different capture methods. Randomised trials solicited events systematically, while registries and pharmacovigilance systems depended on clinician reporting, which the pediatric pharmacovigilance review described as prone to under-reporting (PMID 22748689).
• Different populations. The KIGS analysis covered many diagnoses treated in routine care (PMID 36102184), whereas the idiopathic short stature literature dealt with children without GH deficiency (PMID 40848513).
• Different follow-up. The network meta-analysis reported that trial durations for long-acting products were short relative to the exposure history of daily somatropin (PMID 38580693).
• Different endpoints beyond safety. The systematic review that included quality of life, adherence and cost-effectiveness reported outcomes that no single trial measured alone (PMID 37236413).

What the cited literature does not establish

Several boundaries are worth stating plainly, because they are frequently blurred in general discussion of GH.

1. No cited paper evaluated GH or GH-releasing peptides for cosmetic, anti-ageing or athletic purposes in healthy adults. The doping review discussed such use as a misuse scenario with associated risks rather than as a studied therapy (PMID 36736729).
2. Safety data are indication-specific. Findings reported in children with GHD (PMID 36102184) were not presented as transferable to adults with other conditions, such as the neuromuscular population studied in the 2025 FSHD trial (PMID 40900971).
3. Weekly and daily products are not identical. Comparative trials reported differences in local tolerability even where systemic adverse events were similar (PMID 35405011).
4. Genetic and syndromic contexts add monitoring questions that the Noonan syndrome review discussed separately from general GH safety (PMID 31115197).

How this page fits with the growth hormone course

This page is limited to adverse-event and safety reporting: what researchers measured, how they measured it, and what they wrote in their conclusions. PeptideU's separate growth hormone course covers the underlying physiology, the GH–IGF-1 axis, how the different recombinant and long-acting molecules were designed, and how trial endpoints such as height velocity are defined. Readers looking for mechanism and study-design background will find it there; readers looking for the safety record will find it here. Neither resource provides protocols, dosing instructions or product recommendations.

Again, this page is for educational purposes only and is not medical advice; consult a licensed physician for individual assessment. Nothing above should be read as an evaluation of any product, and no cited study examined unapproved or research-use-only material.

References

• Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin (Revista Clínica Española, 2023)
• Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study (The Journal of Clinical Endocrinology and Metabolism, 2022)
• Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort (The Journal of Clinical Endocrinology and Metabolism, 2022)
• Efficacy, safety, and outcomes of growth hormone treatment in children with idiopathic short stature (Growth Hormone & IGF Research, 2025)
• Pharmacovigilance in children (Archives de Pédiatrie, 2012)
• Long-acting growth hormone in the treatment of growth hormone deficiency in children: a systematic literature review and network meta-analysis (Scientific Reports, 2024)
• Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study (The Journal of Clinical Endocrinology and Metabolism, 2023)
• Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial (The Journal of Clinical Endocrinology and Metabolism, 2021)
• Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis (Pharmacological Research, 2023)
• Study of Testosterone and Recombinant Human Growth Hormone in Facioscapulohumeral Muscular Dystrophy (Neurology: Genetics, 2025)
• Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial (The Journal of Clinical Endocrinology and Metabolism, 2020)
• Growth and Growth Hormone Treatment in Noonan Syndrome (Pediatric Endocrinology Reviews, 2019)