Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature

When children with precocious puberty dependent on luteinizing hormone-releasing hormone (LHRH) are given an LHRH agonist, their adult height is augmented. Some clinicians prescribe this treatment to increase height in short adolescents. This randomized trial sought to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty. The hypothesis tested was that a 4-year course of treatment would increase adult height by delaying senescence of the growth plate, thereby prolonging the time during which linear growth takes place. Participating were 50 adolescents, 32 girls and 18 boys, whose predicted adult height was at least 2.25 standard deviations (SD) below the population mean (average, 33 ′ 1.2 SD). In all cases, the hand and wrist epiphyses were unfused. Using a double-blind design, 26 subjects received the LHRH agonist deslorelin in a dose of 4 μg/kg given each evening by subcutaneous injection for a mean of 3.5 years. The remaining 24 subjects received a placebo for a mean of 2.1 years. Adult height was measured when bone age was greater than 16 years in girls, or 17 years in boys, and when the growth rate was less than 1.5 cm per year. All participants had midpubertal peak LH responses to LHRH at the outset. LHRH-stimulated levels of both LH and follicle-stimulating hormone declined during agonist therapy. When adult height was reached, those given agonist therapy were older than placebo recipients (20.5 vs. 18 years) and were also taller. Treatment increased the SD score for height by 0.6 (95% confidence interval [CI], 0.2-0.9). Height was 4.2 cm greater on average (95% CI, 1.7-6.7) than the initially predicted adult height. Adult height was significantly greater in subjects given LHRH than in those receiving placebo. This was true both for adolescents with idiopathic short stature and those with a growth-limiting syndrome. Bone age increased less in actively treated subjects than in the placebo group, but there was no significant difference at the time adult height was reached. At adult height, those given agonist therapy had lower vertebral bone mineral density at the time of adult height than did placebo recipients. Educational achievement was comparable in the 2 groups. Treatment did not appear to influence secondary sexual development. These findings affirm the value of LHRH agonist treatment for moderately increasing adult height in short adolescents without precocious puberty. The major side effect is a decrease in bone mineral density. In most cases the potential benefit of agonist therapy will not outweigh the risks, and the investigators do not recommend its routine use in these adolescents.