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Multicenter Study
. 2023 Mar 17:14:1113750.
doi: 10.3389/fendo.2023.1113750. eCollection 2023.

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height

Hilde Dotremont  1   2 , Annick France  1   2 , Claudine Heinrichs  3 , Sylvie Tenoutasse  3 , Cécile Brachet  3 , Martine Cools  4 , Kathleen De Waele  4 , Guy Massa  5 , Marie-Christine Lebrethon  6 , Inge Gies  7 , Jesse Van Besien  7 , Christine Derycke  8 , Mathieu Ziraldo  9 , Jean De Schepper  4   7 , Véronique Beauloye  9 , Stijn Verhulst  1   2 , Raoul Rooman  10 , Marieke den Brinker  1   2
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Free PMC article
Multicenter Study

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height

Hilde Dotremont et al. Front Endocrinol (Lausanne). .
Free PMC article

Abstract

Objectives: To improve adult height in pubertal girls with a poor height prediction, treatment with growth hormone (GH) can be used in combination with a gonadotropin releasing hormone agonist (GnRHa), to delay closure of the growth plates. However, there are few studies to support this practice, and they show conflicting results. The objective of this trial is to assess the safety and efficacy of this combination treatment in early pubertal girls with a short predicted height, in comparison with matched controls.

Design patients and methods: We designed an open-label, multicenter, interventional case-control study. Early pubertal girls with predicted adult height (PAH) below -2.5 SDS, were recruited in tertiary care centers in Belgium. They were treated for four years with GH and GnRHa. The girls were followed until adult height (AH) was reached. AH vs PAH, AH vs Height at start, and AH vs Target Height (TH) were evaluated, as well as safety parameters. Control data were assembled from historical patient files or from patients who preferred not to participate in the study.

Results: Sixteen girls with mean age ( ± SD) at start of 11.0 years (± 1.3) completed the study protocol and follow-up. Their mean height ( ± SD) increased from 131.3 ± 4.1 cm (-2.3 ± 0.7 SDS) at start of treatment to 159.8 ± 4.7 cm (-1.1 ± 0.7 SDS) at AH. In matched controls, height increased from 132.3 ± 4.2 cm (-2.4 ± 0.5 SDS) to 153.2 ± 3.4 cm (-2.1 ± 0.6 SDS) (p<0.001). AH surpassed initial PAH by 12.0 ± 2.6 cm in treated girls; and by 4.2 ± 3.6 cm in the controls (p<0.001). Most treated girls reached normal adult height (>-2SD) (87.5%) and 68.7% reached or superseded the target height (TH), which was the case in only a minority of the controls (37.5% and 6.2%, respectively) (p= 0.003 and 0.001). A serious adverse event possibly related to the treatment, was a fracture of the metatarsals.

Conclusion: A four-year GH/GnRHa treatment in early pubertal girls with a poor PAH seems safe and results in a clinically relevant and statistically significant increase in AH compared with matched historical controls.

Clinical trial registration: ClinicalTrials.gov, identifier NCT00840944.

Keywords: adult height; girls; gonadotropin-releasing hormone agonist (GnRHa); growth hormone treatment (GH); puberty; short stature children.

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Conflict of interest statement

Author RR is the owner of the company PendoCon. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart presenting patient disposition.
Figure 2
Figure 2
Evolution of mean height SDS and mean height SDS-target height SDS in treated patients during treatment and follow-up phase.
Figure 3
Figure 3
Adult height compared with predicted adult height and target height in the treated and control patient group.
Figure 4
Figure 4
Yearly bone age progression during treatment and during 2 years of follow-up.
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Grants and funding

This work was supported by the Belgian Society for Pediatric Endocrinology and Diabetes (BESPEED). Study medication was provided by Ferring. Ferring was not involved in the study design, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

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