Anastrozole Increases Predicted Adult Height of Short Adolescent Males Treated With Growth Hormone: A Randomized, Placebo-Controlled, Multicenter Trial for One to Three Years

Mauras, Nelly; Pijem, Lilliam Gonzalez de; Hsiang, Helen Y.; Desrosiers, Paul; Rapaport, Robert; Schwartz, I. David; Klein, Karen Oerter; Singh, Ravinder J.; Miyamoto, A.; Bishop, Kim

doi:10.1097/01.ogx.0000318075.07635.d8

Cited by 19 publications

(31 citation statements)

References 33 publications

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“…Such changes are typical for Scheuermann disease, which is a condition of unknown etiology affecting predominantly males with disease onset in preadolescence. (19) As regards bone fragility, AI treatment in boys has not been associated with impaired bone mass in studies employing DXA, (6,7,9,10) and in the short term, the AI anastrozole had no harmful effect on calcium kinetics in adolescent boys. (20) Additionally, in our cohort of pubertal males with ISS, letrozole treatment stimulated cortical bone growth.…”

Section: Discussionmentioning

confidence: 99%

“…In boys, AI treatment does not influence bone mineral density (BMD) significantly, as evaluated by dual-energy X-ray absorptiometry (DXA). (6,7,9) However, based on serum markers of bone formation and resorption, the treatment appears to suppress bone turnover. (10) In pubertal boys, the treatment stimulates cortical bone growth, (10) but little is known about the treatment effects on trabecular bone mass and bone quality.…”

Section: Introductionmentioning

confidence: 99%

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Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

Hero

Toiviainen-Salo

Wickman

et al. 2010

Journal of Bone and Mineral Research

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Aromatase inhibitors (AIs), blockers of estrogen biosynthesis, delay bone maturation and therefore are used increasingly to promote growth in children and adolescents with growth disorders. The effects of treatment on skeletal health are largely unknown. Since estrogen deficiency is associated with various detrimental skeletal effects, we evaluated in this cross-sectional posttreatment study vertebral body morphology, dimensions and endplates, and intervertebral disks by the use of magnetic resonance imaging (MRI) in two cohorts of males previously treated with the AI letrozole or placebo. Males with idiopathic short stature received treatment with letrozole or placebo for 2 years during prepuberty or early puberty; males with constitutional delay of puberty received letrozole or placebo in combination with low-dose testosterone for 1 year during early or midpuberty. In males with idiopathic short stature, mild vertebral body deformities were found in 5 of 11 (45%) letrozole-treated subjects, whereas in the placebo group no deformities were detected ( p ¼ .01). In the cohort of males with constitutional delay of puberty, a high prevalence of endplate and intervertebral disk abnormalities was observed in both the letrozole-and the placebo-treated groups. We conclude that AI therapy during prepuberty or early puberty may predispose to vertebral deformities, which probably reflect impaired vertebral body growth rather than impaired bone quality and compression fractures. If AIs are used in growth indications, follow-up of vertebral morphology is indicated. ß

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

Hero

Toiviainen-Salo

Wickman

et al. 2010

Journal of Bone and Mineral Research

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“…Current data involving the use of AIs in growth disorders have been generally promising with respect to safety profiles. 7,9,11,12 However, additional studies are required to establish the long-term side effects of treatment with AIs in this patient group, including the evaluation of their impact on later fertility, lipid profiles, and bone mineral density.…”

Section: Discussionmentioning

confidence: 99%

“…In 1 study of 52 patients with GH deficiency, anastrozole in combination with GH therapy was shown to increase predicted adult height (by 6.7 cm vs 1.0 cm with GH alone) while maintaining normal pubertal progression. 7 A randomized controlled trial of boys with constitutional pubertal delay treated with the AI letrozole plus testosterone (N = 9) for 1 year during adolescence significantly improved near-final adult heights compared with testosterone with placebo. 8 In 1 study of 28 children with 21-hydroxylase deficiency, the combination of a reduced dose of hydrocortisone with an antiandrogen (flutamide) and an AI (testolactone) slowed bone maturation while maintaining growth velocity compared with a conventional high-dose glucocorticoid regimen.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone With Aromatase Inhibitor May Improve Height in CYP11B1 Congenital Adrenal Hyperplasia

et al. 2017

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With an estimated prevalence of 1 in 100 000 births, 11β-hydroxylase deficiency is the second most common form of congenital adrenal hyperplasia (CAH) and is caused by mutations in CYP11B1. Clinical features include virilization, early gonadotropin-independent precocious puberty, hypertension, and reduced stature. The current mainstay of management is with glucocorticoids to replace deficient steroids and to minimize adrenal sex hormone overproduction, thus preventing virilization and optimizing growth. We report a patient with CAH who had been suboptimally treated and presented to us at 6 years of age with precocious puberty, hypertension, tall stature, advanced bone age, and a predicted final height of 150 cm. Hormonal profiles and genetic analysis confirmed a diagnosis of 11β-hydroxylase deficiency. In addition to glucocorticoid replacement, the patient was commenced on growth hormone and a third-generation aromatase inhibitor, anastrozole, in an attempt to optimize his growth. After the initiation of this treatment, the patient’s growth rate improved significantly and bone age advancement slowed. The patient reached a final height of 177.5 cm (0.81 SD score), 11.5 cm above his mid-parental height. This patient is only the second reported case of the use of an aromatase inhibitor in combination with growth hormone to optimize height in 11β-hydroxylase-deficient CAH. This novel treatment proved to be highly efficacious, with no adverse effects. It may therefore provide a promising option to promote growth in exceptional circumstances in individuals with 11β-hydroxylase deficiency presenting late with advanced skeletal maturation and consequent short stature.

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“…3,[66][67][68] Using aromatase inhibitors in adolescent boys on GH therapy may also increase adult height potential. [69][70][71] Combination of GnRHa and aromatase inhibitor may have even more benefit in preserving growth potential. 72 …”

Section: Alteration Of Timing Of Skeletal Maturation By Controlling Tmentioning

confidence: 99%

Optimal Therapy of Growth Hormone Deficiency in the Child and Adolescent

Rose¹

2010

European Endocrinology

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Paediatric endocrinologists aspire to provide the best care for children, including improving outcomes in growth hormone deficiency (GHD).The challenging issues are sometimes simple ones, such as which children should be seen in the endocrine clinic for evaluation of their growth, or standards for diagnosis of GHD, or methods of delivering standard therapy for GHD.1 Historically accepted solutions require review as knowledge and technology advance. 2-4This article addresses ways to optimise treatment strategy for children diagnosed with GHD. Optimal therapy of growth disorders depends on accurate diagnosis of the aetiology and identification of the goals of therapy. It is important to understand normal patterns of growth hormone (GH) and insulin-like growth factor (IGF) secretion in order to appreciate differences between normal physiology and hormone patterns induced by therapy. Finally, monitoring for efficacy and safety, identification of interfering factors and making appropriate dose adjustment are all part of optimising GH therapy in childhood GHD. Accurate DiagnosisMany factors besides GH participate in the regulation of normal growth (nutrition, thyroid hormone, genetics, prenatal health, family growth patterns and psychosocial adjustment [see Figure 1]). GH has been administered to children with severe GHD since 1958. Of course, there is no difficulty in making the diagnosis of GHD when the condition is severe. However, with the increasing availability of synthetic recombinant GH, GH therapy has been used in more conditions (see Figure 2). 5 There continues to be controversy about methods for accurate diagnosis of milder degrees of GHD, as well as controversy about which children should be treated with GH.Standardisation of GH assays and cutoff values for normal GH secretion may permit more uniform diagnosis, enabling therapy decisions to be based on reliable data from assays. Goals of TherapyThe purpose of GH treatment must be considered. GH therapy clearly speeds up linear growth in the GHD child and adolescent. However, GHD leads to metabolic effects in addition to slowed linear growth. In untreated GHD, body composition is altered with increased fat mass, decreased lean body mass and decreased accrual of bone mineral. 8-10In addition, individuals with GHD may have decreased exercise tolerance and a sense of fatigue, along with a raised risk for AbstractOptimal therapy of growth disorders depends on accurate diagnosis and clear goals for therapy. Understanding normal patterns of growth hormone (GH) and insulin-like growth factor (IGF) secretion are necessary to appreciate the different hormone pattern induced by therapy.Finally, monitoring efficacy and safety, identifying interfering factors and adjusting doses are all part of optimising GH therapy in childhood GH deficiency (GHD). Prevention of development of GHD would avoid the need for therapy. Options for optimising GH therapy in childhood GHD include initiating treatment as young as possible, facilitating adherence to a therapy plan and adjusti...

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Anastrozole Increases Predicted Adult Height of Short Adolescent Males Treated With Growth Hormone: A Randomized, Placebo-Controlled, Multicenter Trial for One to Three Years

Cited by 19 publications

References 33 publications

Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

Vertebral morphology in aromatase inhibitor–treated males with idiopathic short stature or constitutional delay of puberty

Growth Hormone With Aromatase Inhibitor May Improve Height in CYP11B1 Congenital Adrenal Hyperplasia

Optimal Therapy of Growth Hormone Deficiency in the Child and Adolescent

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