A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of Luteinizing Hormone-Releasing Hormone Analog (LHRHa) in Pubertal Patients With Extreme Short Stature

Children with extreme short stature and their families frequently experience significant psychological stress related to concerns about adult height. Additionally, extreme short stature often presents life-long emotional, social, and physical obstacles to the affected individual. The onset of puberty in such patients presents a critical management problem because puberty initiates the process of epiphyseal closure that terminates linear growth. Until recently, there was no way to delay the onset of puberty in such patients. The development of synthetic LHRH analogs, however, has provided such a method. Administration of such analogs to children with precocious puberty caused a regression of their clinical signs of puberty, a decrease in their gonadotropins and sex steroids, and a slowing of the rate of bone age advancement. We propose to treat pubertal children with extreme short stature with a long-acting analog of luteinizing hormone-releasing hormone (D-Trp6-Pro9-NEt-LHRHa). The goal of LHRHa treatment in these children is to halt the normal progression into puberty and thereby delay epiphyseal fusion. We postulate that delay of puberty will prolong pre-pubertal growth prior to the pubertal spurt and subsequent epiphyseal fusion, and thus will enhance ultimate height. This study will test this hypothesis through a double-blind, randomized comparison of the effect of LHRHa and placebo on final adult height. Patients will be treated with LHRHa or placebo for 4 years, and will then be followed until they have completed puberty and have stopped growing.