ESPEYB16 7. Puberty Treatment (2 abstracts)
7.15. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial
Varimo T , Huopio H , Kariola L , Tenhola S , Voutilainen R , Toppari J , Toiviainen-Salo S , Hämäläinen E , Pulkkinen MA , Lääperi M , Tarkkanen A , Vaaralahti K , Miettinen PJ , Hero M & Raivio T
To read the full abstract: Lancet Child Adolesc Health. 2019 Feb;3(2):109–120
This randomised, controlled, open-label trial at four paediatric centres in Finland evaluates aromatase inhibition with letrozole to induce puberty in boys with constitutional delay of growth and puberty.
Treatment of delayed puberty aims to promote pubertal development and skeletal growth, while avoiding early epiphyseal maturation and gonadal injury. The aromatase inhibitor letrozole inhibits the conversion of androstenedione to estrone, and testosterone to estradiol. Hence, letrozole lowers estrogen concentrations and delays epiphyseal maturation in boys (1–3). By decreasing central feedback inhibition, letrozole also activates gonadotropin secretion and thus promotes testicular growth and testosterone secretion (1, 2).
Boys aged at least 14 years with constitutional delay of growth and puberty, who wanted medical intervention and exhibited the first signs of puberty, were randomly assigned to receive oral letrozole 2·5 mg once daily for 6 months (n=15) or standard treatment: 6× 4-weekly intramuscular injections of low-dose (~1 mg/kg) testosterone (n=14). At 12-months, both letrozole and testosterone treatments induced similar changes in Tanner stage. Additionally, letrozole was more efficacious than testosterone in promoting testicular growth (+7.2 mls vs. +2.2 mls). Letrozole-induced gonadotropin secretion and high concentrations of intra-testicular testosterone might affect development of seminiferous epithelium. However, circulating concentrations of inhibin B remained stable during epiphyseal maturation.
This study suggests letrozole as an alternative treatment to testosterone for boys with constitutional delay of growth and puberty. Furthermore, it may have advantages to testosterone for testicular growth and potentially also for adult height, by suppressing the rate of bone maturation, although available data on this are yet inconclusive.
References: 1. Wickman S, Dunkel L. 2001 Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E. J Clin Endocrinol Metab. 86: 4887–94.
2. Hero M, Norjavaara E, Dunkel L. 2005 Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial. J Clin Endocrinol Metab. 90: 6396–402.
3. Hero M, Wickman S, Dunkel L. 2006 Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty. Clin Endocrinol. 64: 510–13.
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ESPE Yearbook of Paediatric Endocrinology
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