Introduction: Anastrozole, an aromatase inhibitor, prevents the conversion of androgen to oestrogen, which is required for the adolescent growth spurt and the attainment of peak bone mass. Anastrozole may help minimise bone age (BA) advancement in conditions associated with adrenal androgen excess, such as congenital adrenal hyperplasia (CAH) and premature adrenarche.
Objectives: 1. To describe baseline characteristics and BA parameters of patients with CAH and premature adrenarche treated with anastrozole. 2. To describe the safety profile of anastrozole.
Methods: Retrospective data collection of patients with CAH and premature adrenarche (with BA advancement >2 years) treated with anastrozole. BA was calculated using the Tanner Whitehouse method and/or by Bonexpert Software.
Results: Eleven male patients with classical or non-classical CAH secondary to 21-hydroxylase deficiency received 1mg anastrozole once daily, in addition to hydrocortisone (mean dose 13.66 mg/m2/day), with or without fludrocortisone. All patients were pre-pubertal at treatment initiation; six have since entered puberty, with three requiring GnRH analogue treatment. Anastrozole was started at a mean age of 7.96 years. The mean BA advancement at the start of treatment was 4.37 years. Three patients have recently commenced treatment, so no follow-up data are available. One patient has stopped treatment, with a final height at his mid-parental height. Seven patients remain on anastrozole, with a mean treatment length of 3.55 years. The average change in BA per year was 0.16 years. Liver function was normal in all eight patients who underwent testing. Total cholesterol concentrations were normal in nine patients who were tested. Triglyceride concentrations were elevated in two. Nine patients are known to have a normal bone mass following DEXA scans. Three male patients with premature adrenarche received anastrozole at a mean age of 9.03 years, with a mean BA advancement of 2.82 years. The average change in their BA per year was 0.49 years. All three patients had a normal bone mass, normal total cholesterol concentrations, but with raised triglyceride concentrations.
Discussion: Children with CAH may display a very advanced BA, whilst receiving appropriate doses of hydrocortisone. Some children with premature adrenarche have an advanced BA, in the absence of underlying pathology. Anastrozole treatment in childhood appears to be particularly effective at minimising further BA advancement in CAH. If stopped before the adolescent growth spurt, it may facilitate achievement of target height. It has few side-effects, with no changes in liver function, total cholesterol or bone density reported in these patients.
15 Sep 2022 - 17 Sep 2022