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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
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, an...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064858/ https://www.ncbi.nlm.nih.gov/pubmed/37008942 http://dx.doi.org/10.3389/fendo.2023.1113750 |
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author | Dotremont, Hilde France, Annick Heinrichs, Claudine Tenoutasse, Sylvie Brachet, Cécile Cools, Martine De Waele, Kathleen Massa, Guy Lebrethon, Marie-Christine Gies, Inge Van Besien, Jesse Derycke, Christine Ziraldo, Mathieu De Schepper, Jean Beauloye, Véronique Verhulst, Stijn Rooman, Raoul den Brinker, Marieke |
author_facet | Dotremont, Hilde France, Annick Heinrichs, Claudine Tenoutasse, Sylvie Brachet, Cécile Cools, Martine De Waele, Kathleen Massa, Guy Lebrethon, Marie-Christine Gies, Inge Van Besien, Jesse Derycke, Christine Ziraldo, Mathieu De Schepper, Jean Beauloye, Véronique Verhulst, Stijn Rooman, Raoul den Brinker, Marieke |
author_sort | Dotremont, Hilde |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10064858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100648582023-04-01 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 Dotremont, Hilde France, Annick Heinrichs, Claudine Tenoutasse, Sylvie Brachet, Cécile Cools, Martine De Waele, Kathleen Massa, Guy Lebrethon, Marie-Christine Gies, Inge Van Besien, Jesse Derycke, Christine Ziraldo, Mathieu De Schepper, Jean Beauloye, Véronique Verhulst, Stijn Rooman, Raoul den Brinker, Marieke Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2023-03-17 /pmc/articles/PMC10064858/ /pubmed/37008942 http://dx.doi.org/10.3389/fendo.2023.1113750 Text en Copyright © 2023 Dotremont, France, Heinrichs, Tenoutasse, Brachet, Cools, De Waele, Massa, Lebrethon, Gies, Van Besien, Derycke, Ziraldo, De Schepper, Beauloye, Verhulst, Rooman and den Brinker https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Endocrinology Dotremont, Hilde France, Annick Heinrichs, Claudine Tenoutasse, Sylvie Brachet, Cécile Cools, Martine De Waele, Kathleen Massa, Guy Lebrethon, Marie-Christine Gies, Inge Van Besien, Jesse Derycke, Christine Ziraldo, Mathieu De Schepper, Jean Beauloye, Véronique Verhulst, Stijn Rooman, Raoul den Brinker, Marieke 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064858/ https://www.ncbi.nlm.nih.gov/pubmed/37008942 http://dx.doi.org/10.3389/fendo.2023.1113750 |
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