SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1662808
Efficacy of combined gonadotropin-releasing hormone analogue and growth hormone therapy in girls with central precocious puberty: a systematic review and meta-analysis
Provisionally accepted
- Zhejiang University, Hangzhou, China
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Background Central precocious puberty (CPP) in girls is characterized by premature activation of the hypothalamic-pituitary-gonadal axis, often leading to early epiphyseal closure and compromised adult height. While gonadotropin-releasing hormone analogues (GnRHa) are the standard therapy to suppress puberty and preserve height potential, the benefit of adding growth hormone (GH) to improve height outcomes remains unclear. This work aims to evaluate the efficacy of combined GnRHa and GH therapy compared to GnRHa monotherapy in improving growth outcomes in girls with CPP. Methods A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted up to May 2025. Eligible studies comparing GnRHa + GH combination therapy to GnRHa monotherapy in girls with CPP were included. Primary outcomes included final height and final height minus target height (FH–TH). Secondary outcomes included predicted adult height (PAH), height gain, height change during treatment, growth velocity, and bone maturation (ΔBA/ΔCA). Pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated using fixed-or random-effects models based on heterogeneity. Subgroup analyses were conducted by study design. Results Nine studies were included. Combination therapy significantly improved FH–TH (WMD = 1.01 cm, 95% CI: 0.28 to 1.73; P = 0.006), PAH (WMD = 4.27 cm, 95% CI: 3.47 to 5.08; P < 0.0001), height gain (WMD = 3.45 cm, 95% CI: 1.73 to 5.17; P < 0.0001), height change during treatment (WMD = 3.31 cm, 95% CI: 1.76 to 4.86; P < 0.0001), and growth velocity (WMD = 1.40 cm/year, 95% CI: 0.90 to 1.91; P < 0.0001), with no significant effect on bone maturation (ΔBA/ΔCA) (WMD = 0.01, 95% CI: –0.05 to 0.07; P = 0.77). No significant improvement in final height was observed (WMD = 0.14 cm, 95% CI: –1.66 to 1.94; P = 0.88). Conclusion GH supplementation during GnRHa treatment in girls with CPP enhances short-term growth outcomes without accelerating bone age but does not consistently improve final adult height. Combination therapy may be considered for selected patients with poor growth prognosis; however, further high-quality randomized trials are needed to refine patient selection and optimize treatment strategies.
Keywords: central precocious puberty, gonadotropin-releasing hormone analogue, Growth Hormone, Final height, Height gain, Meta-analysis
Received: 09 Jul 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Jin, Sun, Zhu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haitao Yu, Zhejiang University, Hangzhou, China
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