Effects of leuprorelin acetate microspheres on sex hormones, secondary sexual characteristics, and predicted adult height in early and fast puberty girls: a real-world, single-arm, retrospective cohort study.

BACKGROUND: Gonadotropin releasing hormone analogs (GnRHa) are recommended for both central precocious puberty (CPP) and early and fast puberty, but their benefit on final adult height in later onset cases remains controversial. Boennuokang® leuprorelin acetate microspheres, the first domestic generic formulation, have been approved for CPP, but evidence in early and fast puberty girls is still limited. Considering the complexity of clinical management in early and fast puberty, more real-world studies are needed. Therefore, this study aimed to explore the effect of Boennuokang® leuprorelin acetate microspheres on hypothalamic-pituitary-gonadal (HPG) axis and predicted adult height (PAH) in early and fast puberty girls. METHODS: This real-world, single-arm, retrospective cohort study consecutively enrolled 198 early and fast puberty girls treated with Boennuokang® leuprorelin acetate microspheres at The First Bethune Hospital of Jilin University between January 2022 and November 2023. Early and fast puberty was defined as pubertal onset after the diagnostic age cutoff for CPP, accompanied by progression to the next Tanner stage within 6 months and bone age (BA) advancement exceeding chronological age (CA) progression. Baseline variables were collected from the electronic medical record. Tanner stage was assessed by pediatric endocrinologists, sex hormones were measured using standardized biochemical assays, uterine length was evaluated by pelvic ultrasonography, BA was assessed using the Greulich Pyle method, and PAH was calculated using the Bayley-Pinneau method. Follow-up assessments were performed at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3), and 18 (T4) months. Longitudinal changes were analyzed using repeated measures analysis of variance (ANOVA) or Friedman tests. RESULTS: The mean CA and BA of girls were 9.73±0.99 and 12.08±0.82 years, respectively. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol decreased after 18 months of treatment (all P<0.001). Specifically, the median [quartile 1 (Q1)-quartile 3 (Q3)] LH decreased from 2.7 (2.23-3.51) mIU/mL at T0 to 0.66 (0.48-1.22) mIU/mL at T4; the median (Q1-Q3) FSH decreased from 5.27 (4.82-6.10) mIU/mL at T0 to 2.00 (1.56-2.42) mIU/mL at T4; the median estradiol decreased from 163.50 (129.00-195.00) pmol/L at T0 to 36.70 (36.70-36.70) pmol/L at T4. Of note, the proportions of girls in the Tanner stage B5 exhibited a decreasing trend over time. The length of uterus decreased after 18 months of treatment (P<0.001). BA/CA ratio (P<0.001) and growth velocity (P=0.002) decreased over time. PAH increased, and loss in growth potential [genetic target height (GTH) minus PAH] decreased over time (both P<0.001). Body mass index initially increased after 3 months of treatment, then showed a reducing trend until month 18 (P=0.005). CONCLUSIONS: Boennuokang® leuprorelin acetate microspheres are associated with suppression of the HPG axis and increased PAH in early and fast puberty girls.