ESPE Abstracts

Central precocious puberty (CPP) is effectively treated by inhibition of GnRH signaling through GnRH receptor desensitization with depot GnRH agonists (dGnRHa), but the first injection is associated with a surge in LH and FSH (flare) that proportionally increases estradiol levels. When estradiol levels drop, usually within a fortnight, vaginal bleeding may be seen in a small number of girls. Although dGnRHa that use higher, longer-acting doses are increasingly being used in girls with CPP, as they reduce the number of injections/year, the magnitude of the flare caused by each of them has not been compared. One concern that pediatric endocrinologists may have when administering higher doses of dGnRHa is the possibility of greater flare with unwanted consequences such as vaginal bleeding.

Objective: To compare gonadotropin levels during the flare in the first dose of two dGnRHa preparations that differ in dose, intervals, and route of administration in girls with CPP.

Methods: 29 CPP girls from our center were included; n = 17 received Triptorelin 3.75 mg intramuscular route monthly (Trip 3.75) and n = 12 received Leuprolide 45 mg subcutaneous route biannually (Leu 45) as first dose of treatment (data of Leu 45 were obtained from TOL2581A trial). The patients were not randomized to treatment. LH and FSH levels were measured (by ECLIA) at 3 hrs (Trip 3.75 group) and at 4 hrs (Leu 45 group). Clinical characteristics and gonadotropins levels were assessed.

Results: Chronological age (CA), bone age (BA), BA-CA, breast Tanner stage, growth velocity (GV) and BMI were comparable between groups\.No patients experienced vaginal bleeding. The median LH flare was 15.5(7.8-46.8) IU/L in Trip 3.75 group and 26.4(14.4–62.9) IU/L in the Leu 45 group (P = NS). The median FSH flare was 19.3(11.6-38.6) IU/L in Trip 3.75 group and 18(6.9-30.5) in Leu 45 group (P = NS).

Conclusion: Similar LH-FSH flare was observed in both groups. Leuprolide 45 mg, long-acting, biannual administration did not induce a significant higher gonadotropin flare as compared to the monthly Triptorelin 3.75 mg. This result suggests that there should be no concerns regarding flare when using Leuprolide 45 mg to initiate treatment of CPP in girls.