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Should Skeletal Maturation Be Manipulated for Extra Height Gain?
1Division of Pediatric Endocrinology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, Netherlands.
Abstract:
Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.
Insights
Hormone therapies like GnRH analogues and aromatase inhibitors can influence skeletal maturation in children with growth disorders. Combining these with growth hormone may improve adult height, but more data is needed for aromatase inhibitors.
Area of Science:
- Pediatric Endocrinology
- Growth and Development
- Pharmacology
Background:
- Skeletal maturation can be modulated by altering estrogen exposure.
- Gonadotropin-releasing hormone analogues (GnRHa) halt puberty, while aromatase inhibitors (AIs) block estrogen synthesis.
- These agents are used off-label in children with growth disorders, often with recombinant human growth hormone (rhGH).
Purpose of the Study:
- To review the efficacy and safety of GnRH analogues and aromatase inhibitors, alone or with rhGH, in improving adult height (AH) in children with various growth disorders.
- To assess the impact of these hormonal interventions on children with central precocious puberty, growth hormone deficiency, small-for-gestational age, congenital adrenal hyperplasia, and idiopathic short stature.
Main Methods:
- Review of existing literature on the use of GnRH analogues and aromatase inhibitors in pediatric growth disorders.
- Analysis of studies investigating monotherapy or combination therapy with rhGH.
- Evaluation of reported adult height outcomes and safety profiles.
Main Results:
- GnRHa is effective for achieving normal AH in central precocious puberty; its effect in short children with normal puberty is less clear.
- Co-treatment with GnRHa and rhGH improves AH in specific pediatric populations, including those with GHD, SGA, congenital adrenal hyperplasia, and idiopathic short stature.
- Aromatase inhibitors (letrozole, anastrozole) show potential for increasing AH in some cases, but data is limited, and safety profiles are conflicting.
Conclusions:
- GnRH analogues generally have a favorable safety profile and can improve adult height in conjunction with rhGH for specific pediatric growth conditions.
- Aromatase inhibitors' efficacy and safety in improving adult height require further investigation due to limited data and conflicting reports.
- Optimizing adult height in children with growth disorders may involve tailored hormonal therapies, but careful consideration of evidence and safety is crucial.
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