The effect of treatment with an LH-RH agonist (Buserelin) on gonadal activity growth and bone maturation in children with central precocious puberty

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Abstract
Twenty-five children (23 girls and 2 boys) with central precocious puberty were treated with the LH-RH agonistd-Ser (TBU)6-LHRH (1–9) EA (HOE) 766, Buserelin) by daily subcutaneous injection for a period of 11–18 months. Eight girls and 2 boys previously treated with cyproterone acetate (CPA, 100–150 mg/m2 body surface per day) and the first seven newly diagnosed patients received 2×10 μg Buserelin/kg bodyweight per day for 1 week, followed by a maintenance therapy of 1×10 μg/kg per day. After an initial marked increase, oestrogen (E2) serum levels in girls and testosterone (T) values in boys decreased. After a treatment period of 6–20 weeks the patients received 2×20 μg Buserelin/kg per day for 1 week and thereafter a maintenance dosage of 20 μg/kg per day to obtain full suppression (i.e. E2<50 pmol/l; T<1 nmol/l). The remaining eight patients started directly on 2×20 μg Buserelin/kg per day followed by 1×20 μg/kg per day. All eight girls with menarche before therapy had no further menses. In all girls there was a reduction of palpable breast tissue. Decrease of pubic hair development was observed in 3 girls, an increase was seen in 5 girls, whereas in the remaining 15 girls no change was observed. Both boys had a reduction of testicular volume and of pubic hair. The basal growth rate during the half year preceding Buserelin treatment was elevated in the newly diagnosed patients as compared to the growth rate of the patients previously treated with CPA and to the median growth rate of healthy children. During the first 6 months of treatment the mean growth rate decreased slightly in the patients who had received no previous treatment and increased in the patients previously treated with CPA. During the subsequent year a marked fall of the mean growth rate was observed. Paired comparison of the mean SDS (height/chronological age and height/bone age) and of the mean final height prediction (according to Bayley and Pinneau) of 15 children treated for 18 months revealed no significant change. We conclude that during an observation period of 18 months the daily subcutaneous administration of the LH-RH agonist Buserelin has been a safe and effective method of selectively inhibiting gonadal activity in children with central precocious puberty. With prolonged treatment an improvement of the final height prediction is expected.