664 - Change in First Morning Void Urinary Gonadotropins Over GnRHa Treatment in Chinese Children With Central Precocious Puberty (PUPIL Study)

Ling Hou, Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hebei, China (People's Republic); Yan Sun, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jiinan, Shandong, China (People's Republic); Yanhong Li, Sun YSun Yat-sen University First Affiliated Hospital, Guang Zhou, Guangdong, China (People's Republic); Jiajia Chen, Beijing Children's Hospital, Capital Medical University, Beijing, Beijing, China (People's Republic); Pin Li, Children's Hospital, Shanghai Jiao Tong University, Shanghai, Shanghai, China (People's Republic); La Da, Takeda (China) International Trading Co., Ltd, Shanghai, Shanghai, China (People's Republic); Ziheng Guo, Takeda (China) International Trading Co., Ltd,, Shanghai, Shanghai, China (People's Republic); Xiaoping Luo, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (People's Republic)

Background: Central precocious puberty (CPP) results from premature activation of the hypothalamic–pituitary–gonadal (HPG) axis. First morning void urinary gonadotropins (LH and FSH) have shown correlation with CPP diagnosed by the gonadotropin releasing hormone (GnRH) stimulation test, the current gold standard, and may serve as non-invasive markers for follow up. GnRH agonists such as leuprolide acetate (LA) were approved in China in July 2020 for CPP treatment, yet data on the use in Chinese children remain limited.

Objective: To evaluate the FMV urinary LH and FSH levels and their trends after LA therapy in Chinese children with CPP.

Design/Methods: This is an open-label, multicenter, single-arm, prospective study included a 2-week screening, a 24-week treatment, and 12-week follow-up. All patients received LA depot of 11.25 mg, subcutaneously for every 12 weeks. The primary endpoint was the percentage of patients with suppressed LH surge in the GnRH stimulation test at Week (W) 24. Other endpoints included basal LH and FSH levels of patients at baseline, W24, W36; and the proportion of patients showing decreased first morning void (FMV) urinary Gn at W24 versus baseline. Sensitivity analysis 1 imputed missing W24 data using nearest non-baseline values, and analysis 2 used EDC-captured data. Supplementary analysis included cases with complete data.

Results: Of the 92 screened patients, 79 (85.85%) were enrolled; 98.7% were female and all patients had a mean age of 7.59±1.0 years. The mean BMI (kg/m2) was 16.72±2.06 and bone age was 10.19±1.2 years. At baseline, peak LH, FSH and LH/FSH were 18.58±13.97 IU/L, 14.56±6.71 IU/L and 1.35±0.85, respectively (Table 1). After treatment with LA at W24, FMV urinary LH and urinary FSH were reduced in 62.03 (50.41–72.72) and 63.29 (51.69–73.86) of children respectively (Table 2). In the sensitivity analysis 1, the FMV LH and FSH reduced in 62.03 (50.41-72.72) and 64.56 (52.99-75.00) patients respectively. In the sensitivity analysis 2, the proportion of children with reduced LH was 64.56 (52.99-75.00), with reduced FSH was 63.29 (51.69-73.86). In supplemental analysis, the proportion of children with reduced LH was 66.22 (54.28-76.81); whereas, the proportion of children with reduced FSH was 64.10 (52.44–74.66). The results of sensitivity and supplemental analyses showed reduced LH and FSH slightly higher than main analysis.

Conclusion(s): This study revealed a decreasing trend with LA, which effectively suppressed LH and FMV urinary Gn levels, slowing pubertal progression in children with CPP.

Table 1. Demographic and baseline characteristics of patients with CPP
BA, bone age; BMI, body mass index; CA, chronological age; CPP, central precocious puberty; IQR, interquartile range.

Table 2. Details of patients who had reduced urinary Gn (LH and FSH) at week 24 from baseline.
N is the total number of subjects in each included group.
FSH, follicle-stimulating hormone; Gn, gonadotropin; LH, luteinizing hormone.