Adult Height in Precocious Puberty after Long-Term Treatment with Deslorelin

Abstract

Precocious puberty often leads to short adult height. Since the introduction of luteinizing hormone-releasing hormone (LHRH) agonist treatment for LHRH-dependent precocious hormone (LHRH) agonist treatment for LHRH-dependent precocious puberty in 1979, several reports have shown increased predicted height among LHRH agonist-treated children. To determine whether the LHRH agonist deslorelin can normalize the adult height of children with precocious puberty, we are conducting a long-term pilot study involving 161 children. This report describes the first 44 children to have attained final or proximate adult height. These children were 7.1 +/- 1.2 (mean +/- SD) yr old (bone age 11.8 +/- 1.5 yr) and had been in puberty for 3.1 +/- 0.3 yr at the start of treatment. They were treated with deslorelin (4 micrograms/kg/day sc) for 4.1 +/- 1.3 yr and had been withdrawn from treatment for an average of 2.4 yr at the time of this study (age 13.6 +/- 0.9 yr). Fourteen of the 44 children, who had grown less than 0.5 cm during the previous year, were considered to have attained adult height. The other 30 children had achieved 98.6% of predicted mature height (Bayley-Pinneau method) and were considered to be at proximate adult height. The final or proximate adult height of these 44 children averaged -1.1 SD compared to the adult height of the normal population. This height was significantly greater than the pretreatment height (-1.1 vs. -2.0 SD, P less than 0.01), but significantly less than both the predicted height at the end of treatment (-1.1 vs. -0.5 SD, P less than 0.01) and the target height derived from the mean height of the parents adjusted for the sex of the child (-1.1 vs. 0.1 SD, P less than 0.01). The observation that the Bayley-Pinneau height prediction at the end of treatment overestimated the actual adult height emphasizes the importance of using final height data to assess the ultimate impact of LHRH agonist treatment. It also indicates the need for caution when predicting the adult height of children who are still receiving treatment. We conclude that deslorelin has improved the adult height of these patients but has not fully restored height to the patients' genetic potential. We hypothesize that further improvement will be seen in patients who are treated with less delay and at a younger bone age.

Timing for Discontinuation of Treatment with a Long-Acting Gonadotropin-Releasing Hormone Analog in Girls with Central Precocious Puberty.

“…The velocity of bone maturation slowed and the ABA/ACA ratio remained constant at approximately 0.5 at the second year and later during treatment. These findings are consistent with those in previous reports [4,[6][7][8][9][10][11]16]. In Japanese girls, the pubertal spurt of height occurs at 10 to 11 years of age, and menarche at 12.4 years, indicating that estrogen effects on skeletal maturation are increased at approximately 11 years of age.…”

“…It therefore appears likely that progression of bone maturation slowed at a BA of 11 years in girls treated with TAP-144SR. Similar effects have already been reported for GnRH analogs by several authors [6,10,13], but there are some differences in pubertal bone maturation between girls in Japan and the United Kingdom with the TW-2 method. Characteristically bone maturation in Japanese girls involves earlier epiphyseal closure, which occurs at 14.7 years of age: Therefore, BAs of 12 and 13 years estimated by the original TW-2 method [17] correspond to 11.1 and 12 years by the modified TW-2 method for Japanese girls.…”

“…We and others have reported that GnRH analog treatment is safe and effective and has reversible effects on the function of the hypothalamopituitary-gonadal axis [4][5][6]. Several preliminary reports have suggested that improvement of final height can also be achieved by GnRH analog therapy [7][8][9][10][11]. Estimation of final height, however, has critical limitations even when the BayleyPinneau table [12] is used for prediction of final height.…”

Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty

“…Gonadotropin-releasing hormone (GnRH) agonists are known to provide an effective and safe treatment for truly precocious (onset before 8 years in girls or 9 years in boys) puberty of central origin (CTPP), having been demonstrated to suppress the clinical signs of sexual maturation (1)(2)(3) and to reduce the rate of epiphyseal maturation (4)(5)(6).…”

Dose of LHRH Analog and Growth Velocity Influence Predicted Final Height in Girls with Central Precocious Puberty

“…ported that gonadal suppressive agents such as cyproterone acetate and LHRH analog can effectively regress or arrest pubertal development, but the results of the effect on improvement of final height are still controversial (1)(2)(3)(4)(5)(6)(7). Final height is thought to be influenced by the rate of deceleration of bone age maturation and growth rate during treatment.…”