Key Takeaways
- Weekly growth hormone performs similarly to daily injections in the first six months of treatment.
- A modest growth advantage with weekly therapy appears at around one year, but evidence is not yet definitive.
- Short-term safety and side effect rates are comparable between weekly and daily growth hormone.
- The biggest potential benefit of weekly dosing may be easier long-term adherence rather than stronger drug effects.
Pediatric Growth Hormone Injection Training in Endocrinology Clinic
Growth hormone deficiency (GHD) in children is a chronic condition that usually requires years of treatment. For decades, the standard approach has been daily injections of recombinant human growth hormone (rhGH), a therapy that is effective but often difficult to sustain in real life. Missed doses, injection fatigue, and family burnout are common, especially when treatment extends through childhood.
To address these challenges, long-acting growth hormone formulations designed for weekly dosing have been developed. In 2025, Zhang and colleagues published a large systematic review and meta-analysis examining one such option—pegylated recombinant human growth hormone (PEG-rhGH, marketed as Jintrolong in China)—and compared it with traditional daily growth hormone therapy in children with pediatric growth hormone deficiency (PGHD).
Rather than simply asking whether weekly therapy “works,” this review raises a more meaningful question: does reducing injection frequency change outcomes over time, without introducing new safety concerns?
What the 2025 systematic review examined
The review analyzed ten clinical studies (six randomized controlled trials and four cohort studies) involving 1,393 prepubertal children with PGHD. All studies were conducted in China, where PEG-rhGH is approved for weekly use. The analysis focused on a standard weekly dose of PEG-rhGH (0.20 mg/kg/week) compared with conventional daily rhGH dosing.
The primary outcome was change in height standard deviation score (∆Ht-SDS), a commonly used measure that reflects how a child’s height compares with age- and sex-matched peers. Secondary outcomes included height velocity, insulin-like growth factor-1 (IGF-1) levels, and total adverse events.
Height outcomes: similar early, modestly different at one year
At six months, the review found no meaningful difference in height gains between weekly PEG-rhGH and daily growth hormone. This finding was consistent across both randomized trials and observational cohort studies, suggesting that short-term growth response is broadly comparable between the two regimens.
At twelve months, however, a modest difference emerged. In pooled cohort studies, children receiving PEG-rhGH showed a statistically greater improvement in height standard deviation score compared with those receiving daily injections. While this difference was relatively small, it suggests that growth trajectories may diverge over time.
It is important to interpret this finding carefully. The 12-month advantage was driven primarily by cohort studies rather than randomized trials, which means factors such as treatment adherence, family preference, or follow-up intensity could have influenced results. The review itself acknowledges that patient-level data and real-world adherence measures were not available, limiting certainty about the cause of this difference.
Height velocity: more similar than different
Height velocity—the rate at which children grow in centimeters per year—showed no consistent difference between weekly and daily therapy at most time points. Some individual studies, including a large phase III trial, reported slightly higher velocity with PEG-rhGH, but when pooled across studies, the overall differences were not statistically significant.
This suggests that weekly PEG-rhGH is at least not inferior to daily therapy in stimulating linear growth, even if it does not consistently outperform it across all settings.
IGF-1 levels: higher, but generally within range
IGF-1 is an important biological marker of growth hormone activity and is routinely monitored during treatment. Across the included studies, both weekly and daily growth hormone increased IGF-1 levels as expected.
PEG-rhGH was associated with slightly higher increases in IGF-1 standard deviation scores at several time points, particularly in cohort studies. Importantly, the majority of children remained within the normal reference range, and only a small percentage exceeded commonly used upper thresholds.
These findings suggest that weekly PEG-rhGH produces a sustained biological effect consistent with its longer duration of action, without clear evidence of excessive IGF-1 exposure in the short to medium term.
Safety: comparable in the short to medium term
One of the most important questions for families and clinicians is whether less frequent dosing introduces new risks. In this review, overall adverse event rates were similar between weekly PEG-rhGH and daily growth hormone.
Reported adverse events were typical of growth hormone therapy and included peripheral edema, transient thyroid hormone changes, mild glucose or insulin alterations, headaches, joint or muscle pain, and common childhood infections. No serious adverse events clearly attributable to PEG-rhGH were identified in the included studies, and no growth hormone antibodies were detected.
However, most studies followed patients for one year or less, with only limited data extending to two years. As with all growth hormone therapies, longer-term surveillance is still necessary to evaluate rare or delayed outcomes.
The missing variable: adherence
One of the strongest theoretical advantages of weekly growth hormone therapy is improved adherence. Fewer injections may reduce treatment fatigue, anxiety, and missed doses—factors known to affect long-term growth outcomes.
Notably, this systematic review could not directly evaluate adherence, because most included studies did not measure or report it in a standardized way. This means that while weekly therapy may improve real-world effectiveness, the current evidence cannot definitively separate biological drug effects from behavioral factors related to dosing convenience.
How this review fits with broader research
These findings are consistent with broader research on long-acting growth hormone therapies, though results vary by formulation. A 2024 systematic review and network meta-analysis comparing multiple weekly growth hormone products found that long-acting therapies overall were effective for pediatric growth hormone deficiency, but growth outcomes differed between specific agents, suggesting they should not be viewed as interchangeable. Similarly, the phase 3 heiGHt trial demonstrated that weekly lonapegsomatropin achieved comparable—and in some measures greater—growth responses than daily growth hormone at one year in treatment-naïve children. While these studies evaluated different long-acting formulations than PEG-rhGH, they support the biological plausibility that reduced injection frequency can maintain efficacy when exposure is appropriately sustained.
What this means for clinical decision-making
Taken together, the 2025 review supports several practical conclusions:
- Weekly PEG-rhGH provides growth outcomes comparable to daily growth hormone in children with PGHD.
- A modest advantage in height gain at 12 months is possible, but should be interpreted cautiously.
- Short-term safety appears similar between weekly and daily regimens.
- Treatment adherence, quality of life, and long-term outcomes remain critical—and under-studied—factors.
Choosing between weekly and daily growth hormone therapy is not simply a question of which drug is “better.” It depends on the child’s diagnosis, age, growth response, monitoring plan, family preferences, and access to follow-up care. These decisions are best made collaboratively between families and pediatric endocrinology specialists.
FAQs
What is pediatric growth hormone deficiency (PGHD)?
A medical condition where a child’s body does not produce enough growth hormone to support normal growth and development.
Why is growth hormone used to treat PGHD?
It replaces the missing hormone and helps stimulate normal linear growth, bone development, and metabolic functions.
What is recombinant human growth hormone (rhGH)?
A lab-produced version of human growth hormone that is biologically identical to what the body naturally makes.
What does “long-acting” growth hormone mean?
It refers to formulations designed to stay active in the body longer, allowing weekly injections instead of daily ones.
What is PEG-rhGH?
A form of growth hormone chemically linked to polyethylene glycol (PEG) to slow its breakdown and extend its duration of action.
Why was PEG-rhGH developed?
To reduce injection frequency and potentially improve long-term treatment adherence in children.
Is weekly growth hormone as effective as daily injections?
Current evidence shows similar growth outcomes in the short term, with a possible modest advantage after one year.
What is height standard deviation score (Ht-SDS)?
A statistical measure showing how a child’s height compares to average children of the same age and sex.
Why do studies use Ht-SDS instead of centimeters alone?
It accounts for age, sex, and population norms, making growth changes easier to compare across children.
What is height velocity?
The rate at which a child grows in height over a year, usually measured in centimeters per year.
Did weekly growth hormone increase height velocity more than daily therapy?
Most studies found similar height velocity between weekly and daily treatments.
What is IGF-1 and why is it measured?
Insulin-like growth factor 1 is a hormone stimulated by growth hormone and reflects how strongly treatment is working.
Are higher IGF-1 levels dangerous?
Not necessarily; levels are monitored to stay within a normal range to avoid potential side effects.
Did PEG-rhGH cause excessively high IGF-1 levels?
In most children, IGF-1 levels remained within normal limits during treatment.
What side effects were reported in the studies?
Common effects included mild swelling, temporary thyroid changes, headaches, joint pain, and common infections.
Were serious side effects seen with weekly growth hormone?
No serious treatment-related adverse events were reported in the reviewed studies.
Is weekly growth hormone safer than daily growth hormone?
The short-term safety profiles appear similar based on available data.
How long were children followed in these studies?
Most studies followed children for six to twelve months, with limited data up to two years.
Why does injection frequency matter?
Fewer injections may reduce treatment fatigue and missed doses, which can affect growth outcomes.
Did the studies measure how often children missed doses?
No, adherence was not consistently measured, which is a key limitation of current research.
Are results from China applicable to other countries?
They provide useful data, but differences in healthcare systems and treatment practices should be considered.
Is weekly growth hormone approved everywhere?
Approval varies by country and by specific formulation.
Does weekly growth hormone replace daily therapy for everyone?
No, treatment choice depends on individual medical factors and clinician judgment.
Can weekly growth hormone improve quality of life?
It may reduce stress related to injections, but quality-of-life data are still limited.
What should parents discuss with their child’s endocrinologist?
Treatment options, expected growth outcomes, monitoring plans, side effects, and what dosing schedule best fits the child and family.
Related Reading:
HGH Dosages: The off-label Doses Currently Used for Anti Aging, Weight Loss, and Bodybuilding
HGH Side Effects: Is Growth Hormone Worth the Risks and Are There Safe Alternatives?
Do You Have HGH Deficiency? Symptoms and New Diagnostic Tests Explained
HGH Effects Over Time: What to Expect Month-by-Month
Final Thoughts
The 2025 systematic review by Zhang and colleagues adds meaningful evidence to the growing body of research on long-acting growth hormone therapy. Weekly PEG-rhGH appears to be an effective and generally well-tolerated alternative to daily injections for children with pediatric growth hormone deficiency, with a possible growth advantage emerging over longer follow-up.
At the same time, the review highlights the need for longer, higher-quality studies that incorporate real-world adherence, quality of life, and long-term safety data. As growth hormone therapy continues to evolve, the most important outcomes may depend not only on pharmacology, but also on how well treatments fit into the daily lives of children and their families.
References
Zhang, J., Guo, S., Wang, T., & Chen, Q. (2025). Comparison between long-acting pegylated and daily recombinant human growth hormone for pediatric growth hormone deficiency: A systematic review and meta-analysis. Scientific Reports, 15, Article 26746. https://doi.org/10.1038/s41598-025-10613-x
Zhu, J., Yuan, K., Rana, S., Jakki, S. L., Bhat, A. S., Liang, L., & Wang, C. (2024). Long-acting growth hormone in the treatment of growth hormone deficiency in children: A systematic literature review and network meta-analysis. Scientific Reports, 14(1), 8061. https://doi.org/10.1038/s41598-024-58616-4
Thornton, P. S., Maniatis, A. K., Aghajanova, E., Chertok, E., Vlachopapadopoulou, E., Lin, Z., Song, W., Christoffersen, E. D., Breinholt, V. M., Kovalenko, T., Giorgadze, E., Korpal-Szczyrska, M., Hofman, P. L., Karpf, D. B., Shu, A. D., & Beckert, M. (2021). Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: The phase 3 heiGHt trial. The Journal of Clinical Endocrinology & Metabolism, 106(11), 3184–3195. https://doi.org/10.1210/clinem/dgab529
