Introduction: Formulations and doses of GnRH analogues used to treat idiopathic central precocious puberty (iCPP) may vary with clinician preference or local approvals. Aim of this study is to define factors that affect initial depot leuprolide acetate (LA) dose which suppress hypothalamo-pituitary-gonad (HPG) axis in girls with iCPP.
Methods: A total of 220 girls receiving LA for iCPP were included. LA is started in the dose of 3.75 mg/28 days, and suppression is examined using GnRH test at the 3rd month of treatment. Dose of LA is increased to 7.5 mg/28 days in those who fail the test (peak LH>2 IU/l). Higher dose is similarly tested for suppression of HPG 3 months later. We retrospectively compared clinical and hormonal characteristics of the two populations whose HPG axis was suppressed with low vs high dose of LA. ROC curves were used to determine thresholds for factors (age, body weight [BW], BMI, BMI-SDS, basal LH and estradiol, peak stimulated LH) with an impact on the suppressing dose of LA. We analyzed whether thresholds differentiate the two populations with low or high dose LA, using univariate logistic regression. Pubertal stages were grouped into early (Tanner 2&3) vs advanced (Tanner 4 &5), and impact of pubertal stages were also analyzed. Significant factors in univariate analysis were reevaluated in multiple logistic regression.
Results: Peak stimulated LH in 88.6% of the patients was <2 IU/l under treatment with 3.75 mg LA. Age did not differ between the two different dose populations. The best threshold values that differentiate the two doses were 36.2 kg for BW (AUC:0.934), 20.7 kg/m2 for BMI (AUC: 0.964),+1.64 for BMI-SDS (AUC:0.914), 1.5 mIU/ml for basal LH (AUC:0.71), 41 pg/ml for basal estradiol (AUC:0.898), 17.6 mIU/ml for peak stimulated LH (AUC:0.710)(P<0.001). Univariate analysis indicated BW, BMI and BMI-SDS as well as advanced stage of puberty were associated with higher dose of LA (P <0.001, <0.001, <0.001, 0.02, respectively). Basal LH, estradiol and stimulated LH peak did not differentiate necessity for low or high dose. Multiple logistic regression showed that BW, BMI, and BMI-SDS above the thresholds indicated requirement of high dose LA (P<0.001).
Conclusion: Low dose monthly injections of LA is an effective treatment in majority of girls with iCPP, however higher initial dose may be preferred in patients with BW≥36.2 kg or BMI≥20.7 kg/m2 for effective suppression of HPG axis.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology