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A meta-analysis of combination therapy with gonadotrophin-releasing hormone agonist and growth hormone for children with idiopathic short stature and normal timed puberty

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Abstract

Purpose

The aim of this meta-analysis is to evaluate whether the combination therapy with gonadotrophin-releasing hormone agonist (GnRHa) and recombinant human growth hormone (rhGH) are effective in the treatment of children with idiopathic short stature (ISS) and normal timed puberty by interrogating data from clinical controlled trials.

Methods

Literature retrieval, trail selection, data abstraction and quality assessment were completed independently by two authors. STATA software (version 14.1) was used for data analyses.

Results

This meta-analysis was conducted based on 8 (4 randomized and 4 non-randomized) controlled trials. A total of 245 ISS children with normal timed puberty were financially analyzed. Overall, combination therapy with GnRHa and rhGH can slightly increase final height by 3.70 and 3.43 cm compared with GH treatment alone and no treatment, final height standard deviation score (FHSDS) by 0.10 and 0.22, final height minus predicted adult height (FH-PAH) by 1.5 and 5.32 cm, final height minus predicted adult height (FH-TH) by 7.70 and 4.32 cm, respectively. Subgroup and meta-regression analyses revealed that study type, sample size, GnRHa duration, and percentage of boys were potential sources of between-trial heterogeneity. There was a low probability of publication bias for above comparisons, as indicated by Egger’s tests.

Conclusions

Our meta-analytical findings indicate that the combination therapy with GnRHa and rhGH can slightly increase the final height of ISS children with normal timed puberty, and the effect was not more obvious than GH alone. We do not recommend the combination therapy as a routine treatment for ISS.

Trial registration number

CRD42019133438

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Author contributions

Conceived and designed the article: L.W., Z.Z., W.N. Performed the experiments: B.Z., S.L., W.N. Analyzed the data: B.Z., S.L., Y.Y. Contributed materials/analysis tools: B.Z., J.W., Z.Z. Wrote and revised the paper: B.Z., T.Z., W.N., L.W. All authors read and approved the final manuscript prior to submission.

Funding

This research was supported by Public Service Development and Reform Pilot Project, Beijing Municipal Health Commission (BMR2019-11), Capital’s Funds for Health Improvement and Research (2020-2-2104), and Research Foundation of Capital Institute of Pediatrics (CXYJ-2021-08, QN-2020-09).

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Authors and Affiliations

  1. Department of Child Health Care, Children’s Hospital, Capital Institute of Pediatrics, Beijing, China

    Bo Zhou, Jianhong Wang & Lin Wang

  2. Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China

    Shufang Liu

  3. Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China

    Ting Zhang

  4. Department of Integrated Traditional and Western Medicine, Yantai YuHuangDing Hospital, Shandong, China

    Yuan Yuan

  5. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China

    Wenquan Niu

  6. International Medical Services, China-Japan Friendship Hospital, Beijing, China

    Zhixin Zhang

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  1. Bo Zhou
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Zhou, B., Liu, S., Wang, J. et al. A meta-analysis of combination therapy with gonadotrophin-releasing hormone agonist and growth hormone for children with idiopathic short stature and normal timed puberty. Endocrine 75, 698–708 (2022). https://doi.org/10.1007/s12020-021-02970-0

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