Aromatase inhibitor shown to increase predicted adult height in GH deficient boys

Epiphyseal fusion delayed; pubertal progression remained normal.

Issue: August 2006

BOSTON — In growth hormone deficient boys, use of an aromatase inhibitor was shown to delay epiphyseal fusion and increase predicted adult height, researcher Nelly Mauras, MD, division chief, department of pediatrics, division of endocrinology, Nemours Children’s Clinic, Jacksonville, Fla., reported at The Endocrine Society’s 88th Annual Meeting.

“As compared to placebo, the use of anastrozole [Arimidex, AstraZeneca] for two years in growth hormone-treated adolescent males with growth hormone deficiency resulted in comparable rates of growth and tempo of puberty, with marked decrease in rate of bone age acceleration, significant increases in predicted adult height and comparable rates of bone mineral density accrual,” Mauras said.

“Keeping the growth plates open becomes critical in trying to promote linear growth in growth-retarded children who are in adolescence,” Mauras said.

Slower bone age acceleration

In a double-blind, placebo controlled study, researchers recruited 52 GH deficient boys who had residual height potential (bone age <16 years). They were randomized to continue daily GH treatment of approximately 0.3 mg/kg per week and either 1 mg anastrozole daily or placebo tablets for either 36 months, or until completion of linear growth, which was defined as bone age >16 years and growth velocity <2 cm per year.

The groups were well matched at study entry for age (13.7 and 14.2 years for anastrozole and placebo groups respectively); bone age, (13.6 and 13.5 years); height, (149.8 cm and 151.6 cm), average prior years on GH, (3.5 years and 2.7 years, respectively).

Anastrozole patients had comparable growth velocity to placebo patients at 24 and 36 months.

“In the anastrozole group, however, there was a much lower tempo of bone age acceleration at two years and this was sustained at three years as compared to the placebo group,” Mauras said.

After two years, boys treated with anastrozole had advanced their bone age of +1.8 years from baseline vs. +2.8 years for the placebo group (P<.0001). After three years, the difference was +2.4 years vs. four years for the anstrozole and placebo group, respectively (P=.003).

Increased height

“These changes in the tempo of bone age acceleration translated to changes in predicted adult height,” Mauras said.

At two years, the net increase in predicted adult height as compared to baseline for the anastrozole group was 4.4 cm compared with a 1-cm increase in the height prediction in the placebo group. At 36 months, in a smaller cohort, these differences were further increased to a gain in approximately 7.4 cm in predicted height in the anastrozole group vs. +1 cm in the placebo group.

As the patients of placebo progressed through puberty, there was a natural rise in estradiol concentrations, Mauras said. Estradiol concentrations from baseline dropped in the anastrozole-treated patients, but over time tended to increase again, she said.

Extensive safety data, including glucose and lipid concentrations were comparable in both groups over the course of study as was the rate of bone mineral density accrual as measured by DEXA. Overall the drug was very well tolerated.

Anastrozole was shown to increase adult height potential while maintaining “normal pubertal progression” after two years, results that seem to be holding on the cohort that has completed three years, researchers concluded.

“Estrogen blockade, using aromatase inhibitors offer promise in the treatment of growth-retarded boys in puberty, however, long term follow up is still needed to better assess the safety and efficacy of this approach,” Mauras said. – by Rachel Eskenazi

For more information:

Mauras K, de Pijem LG, Hsiang H, et al. Placebo controlled, double blind, randomized trial of the safety and efficacy of Arimidex in delaying epiphyseal fusion in growth hormone (GH) deficient males in puberty: preliminary results. Presented at: The Endocrine Society’s 88th Annual Meeting; June 26, 2006; Boston.