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

ObjectivesTo 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...

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Hauptverfasser: 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
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creator 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
description ObjectivesTo 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 methodsWe 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. ResultsSixteen 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
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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 methodsWe 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. ResultsSixteen 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&lt;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&lt;0.001). Most treated girls reached normal adult height (&gt;-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. ConclusionA 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.</description><identifier>ISSN: 1664-2392</identifier><identifier>EISSN: 1664-2392</identifier><language>eng</language><publisher>Frontiers Media SA</publisher><subject>adult height ; Biology and Life Sciences ; Endocrinology, Diabetes and Metabolism ; girls ; gonadotropin-releasing hormone agonist (GnRHa) ; growth hormone treatment (GH) ; Medicine and Health Sciences ; puberty ; short stature children</subject><creationdate>2023</creationdate><rights>Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,4010,27839</link.rule.ids></links><search><creatorcontrib>Dotremont, Hilde</creatorcontrib><creatorcontrib>France, Annick</creatorcontrib><creatorcontrib>Heinrichs, Claudine</creatorcontrib><creatorcontrib>Tenoutasse, Sylvie</creatorcontrib><creatorcontrib>Brachet, Cécile</creatorcontrib><creatorcontrib>Cools, Martine</creatorcontrib><creatorcontrib>De Waele, Kathleen</creatorcontrib><creatorcontrib>Massa, Guy</creatorcontrib><creatorcontrib>Lebrethon, Marie-Christine</creatorcontrib><creatorcontrib>Gies, Inge</creatorcontrib><creatorcontrib>Van Besien, Jesse</creatorcontrib><creatorcontrib>Derycke, Christine</creatorcontrib><creatorcontrib>Ziraldo, Mathieu</creatorcontrib><creatorcontrib>De Schepper, Jean</creatorcontrib><creatorcontrib>Beauloye, Véronique</creatorcontrib><creatorcontrib>Verhulst, Stijn</creatorcontrib><creatorcontrib>Rooman, Raoul</creatorcontrib><creatorcontrib>den Brinker, Marieke</creatorcontrib><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><description>ObjectivesTo 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 methodsWe 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. ResultsSixteen 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&lt;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&lt;0.001). Most treated girls reached normal adult height (&gt;-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. ConclusionA 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.</description><subject>adult height</subject><subject>Biology and Life Sciences</subject><subject>Endocrinology, Diabetes and Metabolism</subject><subject>girls</subject><subject>gonadotropin-releasing hormone agonist (GnRHa)</subject><subject>growth hormone treatment (GH)</subject><subject>Medicine and Health Sciences</subject><subject>puberty</subject><subject>short stature children</subject><issn>1664-2392</issn><issn>1664-2392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ADGLB</sourceid><recordid>eNqtjEFOhEAURInRxInOHf4FSIBhULYaCIlx48yCHfk0n-5verpJd-OEA3lPceJiDmBtqpJXVTfRJi2KPM52ZXZ7le-jrfefyao8ScvyeRN9V-PIAsUCaAbwOFJYwI6AkMcLoQNhTz0bDGwNBEUOpwuXzp6DAmXdyRq6jKU1ONjg7MQmdqQJPRt5VUFt5UzABqa5JxdQg2SnPZx5vfJrMcDkaGARaAAcZh1AEUsVHqO7EbWn7Z8_RFVdHV-bWCoyodPcOxIYOovcoROKv6ib5S_qqUvS5v2jPbZN_VI8NXXWHrIqO-T7_dvuv35-AANeePE</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Dotremont, Hilde</creator><creator>France, Annick</creator><creator>Heinrichs, Claudine</creator><creator>Tenoutasse, Sylvie</creator><creator>Brachet, Cécile</creator><creator>Cools, Martine</creator><creator>De Waele, Kathleen</creator><creator>Massa, Guy</creator><creator>Lebrethon, Marie-Christine</creator><creator>Gies, Inge</creator><creator>Van Besien, Jesse</creator><creator>Derycke, Christine</creator><creator>Ziraldo, Mathieu</creator><creator>De Schepper, Jean</creator><creator>Beauloye, Véronique</creator><creator>Verhulst, Stijn</creator><creator>Rooman, Raoul</creator><creator>den Brinker, Marieke</creator><general>Frontiers Media SA</general><scope>ADGLB</scope></search><sort><creationdate>2023</creationdate><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><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-ghent_librecat_oai_archive_ugent_be_01HMRXTXHFB67HF2XS2E2S455K3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adult height</topic><topic>Biology and Life Sciences</topic><topic>Endocrinology, Diabetes and Metabolism</topic><topic>girls</topic><topic>gonadotropin-releasing hormone agonist (GnRHa)</topic><topic>growth hormone treatment (GH)</topic><topic>Medicine and Health Sciences</topic><topic>puberty</topic><topic>short stature children</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dotremont, Hilde</creatorcontrib><creatorcontrib>France, Annick</creatorcontrib><creatorcontrib>Heinrichs, Claudine</creatorcontrib><creatorcontrib>Tenoutasse, Sylvie</creatorcontrib><creatorcontrib>Brachet, Cécile</creatorcontrib><creatorcontrib>Cools, Martine</creatorcontrib><creatorcontrib>De Waele, Kathleen</creatorcontrib><creatorcontrib>Massa, Guy</creatorcontrib><creatorcontrib>Lebrethon, Marie-Christine</creatorcontrib><creatorcontrib>Gies, Inge</creatorcontrib><creatorcontrib>Van Besien, Jesse</creatorcontrib><creatorcontrib>Derycke, Christine</creatorcontrib><creatorcontrib>Ziraldo, Mathieu</creatorcontrib><creatorcontrib>De Schepper, Jean</creatorcontrib><creatorcontrib>Beauloye, Véronique</creatorcontrib><creatorcontrib>Verhulst, Stijn</creatorcontrib><creatorcontrib>Rooman, Raoul</creatorcontrib><creatorcontrib>den Brinker, Marieke</creatorcontrib><collection>Ghent University Academic Bibliography</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dotremont, Hilde</au><au>France, Annick</au><au>Heinrichs, Claudine</au><au>Tenoutasse, Sylvie</au><au>Brachet, Cécile</au><au>Cools, Martine</au><au>De Waele, Kathleen</au><au>Massa, Guy</au><au>Lebrethon, Marie-Christine</au><au>Gies, Inge</au><au>Van Besien, Jesse</au><au>Derycke, Christine</au><au>Ziraldo, Mathieu</au><au>De Schepper, Jean</au><au>Beauloye, Véronique</au><au>Verhulst, Stijn</au><au>Rooman, Raoul</au><au>den Brinker, Marieke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><date>2023</date><risdate>2023</risdate><issn>1664-2392</issn><eissn>1664-2392</eissn><abstract>ObjectivesTo 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 methodsWe 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. ResultsSixteen 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&lt;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&lt;0.001). Most treated girls reached normal adult height (&gt;-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. ConclusionA 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.</abstract><pub>Frontiers Media SA</pub><oa>free_for_read</oa></addata></record>
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source Ghent University Academic Bibliography; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access
subjects adult height
Biology and Life Sciences
Endocrinology, Diabetes and Metabolism
girls
gonadotropin-releasing hormone agonist (GnRHa)
growth hormone treatment (GH)
Medicine and Health Sciences
puberty
short stature children
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
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