Treatment with a Luteinizing Hormone–Releasing Hormone Agonist in Adolescents with Short Stature

Abstract

BACKGROUND: Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist increases adult height in children with LHRH-dependent precocious puberty and is prescribed by some practitioners to augment height in short adolescents. We performed a randomized clinical trial to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty. METHODS: Fifty short adolescents (18 boys and 32 girls) with low predicted adult height (mean [±SD], 3.3±1.2 SD below the population mean) received either placebo (24 subjects) or an LHRH agonist (26 subjects). The mean (±SD) duration of treatment was 3.5±0.9 years in the LHRH-agonist group and 2.1±1.2 years in the placebo group (P<0.001). Adult height was measured when bone age exceeded 16 years in girls and 17 years in boys and when the rate of growth was less than 1.5 cm per year. RESULTS: Forty-seven adolescents (94 percent) were followed until they attained adult height. At the time adult height was achieved, the subjects who had been treated with an LHRH agonist were older than those who had received placebo (20.5±2.1 years vs. 18.0±2.5 years, P=0.01) and were taller (standard-deviation score, 2.2±1.1 vs. -3.0±1.2; P=0.01). Analysis of covariance showed that LHRH-agonist treatment resulted in an increase of 0.6 (95 percent confidence interval, 0.2 to 0.9) in the standard-deviation score for height, or an increase of 4.2 cm (95 percent confidence interval, 1.7 to 6.7), over the initially predicted adult height (P=0.01). Treatment with an LHRH agonist resulted in significantly greater adult height than did placebo in boys and girls, in adolescents with idiopathic short stature, and in those who had a growth-limiting syndrome. The principal adverse event in the LHRH-agonist group was decreased accretion of bone mineral density (mean lumbar vertebral bone mineral density at the time adult height was achieved, 1.6±1.2 SD below the population mean, vs. 0.3±1.2 SD below the population mean in the placebo group; P<0.001). CONCLUSIONS: Treatment with an LHRH agonist for 3.5 years increases adult height by 0.6 SD in adolescents with very short stature but substantially decreases bone mineral density. Such treatment cannot be routinely recommended to augment height in adolescents with normally timed puberty.