Gonadotropin-Releasing Hormone Agonists and Sexual Growth in Precocious, Early, and Normal Puberty

Abstract

Gonadotropin-releasing hormone agonists are considered the treatment of choice for central precocious puberty. They are also administered for postponing puberty in short children with a poor final height prognosis in order to delay epiphyseal closure and prolong their growth period, so as to augment the final height outcome. Addressed in this review are several aspects of the effect of gonadotropin-releasing hormone agonists treatment on pubertal growth spurt and final height, including the following issues: the hormonal regulation of pubertal growth in normal and in precocious puberty; the variable pace of pubertal progression in central precocious puberty; the effect of gonadotropin-releasing hormone agonists treatment on bone elongation and maturation in boys and in girls; growth following interruption of gonadotropin-releasing hormone agonists treatment; assessment of the efficacy of gonadotropin-releasing hormone agonists treatment on final height outcome in patients with central precocious puberty and in children with short stature and normal puberty, in light of the imprecision in height prediction methods. Review of the literature dealing with gonadotropin-releasing hormone agonists treatment in central precocious puberty indicated that in untreated patients with slowly progressive variants height outcome was not compromised. In girls with progressive CPP, gonadotropin-releasing hormone agonists appeared to increase final height when onset of puberty occurred before the age of 8 years, whereas no height benefit was demonstrated in those treated after 8 years. Although data on the effect of treatment in boys were sparse, GnRHa appeared to improve their final height. In both sexes the most appropriate time for interrupting the treatment remains controversial. When used outside the context of central precocious puberty gonadotropin-releasing hormone agonists treatment induced a relatively small height gain unless administered for more than 3 years. This extended treatment period could be associated with psychological distress due to delayed puberty and decreased bone mass accumulation. In an attempt to avoid these adverse effects and to increase final height in gonadotropin-releasing hormone agonists-treated short children, growth hormone treatment was added. The dual therapy appeared to be beneficial in growth hormone-deficient children with relatively early onset of puberty, in children with idiopathic short stature, and in children with persistent short stature after intrauterine growth retardation, with an additional final height gain of approximately 4–10 cm. However, as long-term side effects are still insufficiently known, this treatment has not been generally advised.