Treatment of progressive central precocious puberty with leuprorelin depot

Background:The suppression of the pituitary secretion of gonadotropins and subsequently the suppression of gonadal sex steroid production is the main therapeutic goal in the treatment of children with central precocious puber ty. We investigated the efficacy of a depot formulation of the GnRH agonist leuprorelin for subcutaneous injection in a prospective multicentric study according to the guidelines of Good Clinical Practice. Patients and methods: Forty girls with progressive central precocious puber ty aged between 1.5 and 8.7 years were included in the study. Bone age rang ed between 2.8 and 12.25 years. Age at thelarche was 1.1 to 7.75 years. All girls showed a pubertal response to GnRH. Bone age was accelerated and bon e maturation was progressively increased. Growth was accelerated for age. A ll hormonal analyses and bone age determination were performed centrally. I nitially treatment was done by subcutaneous injection of leuprorelin Depot every 30+/-2 days in a dose of 90 mu g/kg and later in a dose of 1/2 ampoul e (1.88 mg) or 1 ampoule (3.75 mg) at a body weight of below 20 kg or equal to or above 20 kg, respectively. Results: The percentage of adequately suppressed GnRH tests (stimulated LH <5 IU/I) increased with treatment duration (86% after 6 months, 95% after 1 year) and reached 100% after 2 years of treatment. Breast development was arrested or showed regression in 37 of 40 patients. Growth was normalized i n the majority of girls (growth rate SDS 1.3+/-1.3 in the 2nd year of treat ment). Furthermore, bone maturation was significantly slower during than be fore treatment: Delta bone age/Delta chronological age 0.9+/-0.5 and 0.6+/- 0.4 during year 1 and 2, respectively (both p<0.05 vs pretreatment). Severe side effects were not encountered. Withdrawal bleedings were seen in six p atients (15%) in the initial phase of therapy. Menstruations did not occur with further treatment. Conclusions: Treatment with subcutaneous leuprorelin depot leads to a suffi cient suppression of pituitary gonadotropin secretion in girls with progres sive central precocious puberty. With this treatment regimen it is possible to stop pubertal development, avoid precocious menstruations, normalize gr owth rate, and decrease the rate of bone maturation. The profile of unwante d side effects is favorable.