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.
Leuprorelin acetate microspheres may suppress sex hormones and increase predicted adult height in girls with early and fast puberty, but the clinical relevance of these findings needs further investigation.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
This study measured the effects of Boennuokang® leuprorelin acetate microspheres on sex hormones and predicted adult height in 198 early and fast puberty girls. Treatment resulted in significant decreases in luteinizing hormone, follicle-stimulating hormone, and estradiol over 18 months. Predicted adult height increased, and growth potential loss decreased during the same period.
Abstract
<h4>Background</h4>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<sup>®</sup> 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<sup>®</sup> leuprorelin acetate microspheres on hypothalamic-pituitary-gonadal (HPG) axis and predicted adult height (PAH) in early and fast puberty girls.<h4>Methods</h4>This real-world, single-arm, retrospective cohort study consecutively enrolled 198 early and fast puberty girls treated with Boennuokang<sup>®</sup> 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.<h4>Results</h4>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).<h4>Conclusions</h4>Boennuokang<sup>®</sup> leuprorelin acetate microspheres are associated with suppression of the HPG axis and increased PAH in early and fast puberty girls.
Background
This study addresses the effects of gonadotropin-releasing hormone analogs (GnRHa) on the hypothalamic-pituitary-gonadal (HPG) axis and predicted adult height in girls experiencing early and fast puberty. Previous studies have shown mixed results regarding the benefits of GnRHa on final adult height, particularly in cases of later onset. This research is significant as it aims to provide real-world evidence on the impact of leuprorelin acetate microspheres in this population.
Methods
This was a real-world, single-arm, retrospective cohort study involving 198 early and fast puberty girls treated with Boennuokang® leuprorelin acetate microspheres at The First Bethune Hospital of Jilin University from January 2022 to November 2023. The study defined early and fast puberty based on specific Tanner stage progression and bone age advancement criteria. Assessments included hormone levels, uterine length, and predicted adult height at baseline and follow-up points (3, 6, 12, and 18 months).
Results
After 18 months of treatment, median LH decreased to 0.66 (0.48-1.22) mIU/mL, FSH decreased to 2.00 (1.56-2.42) mIU/mL, and estradiol decreased to 36.70 (36.70-36.70) pmol/L, all with P<0.001. The BA/CA ratio and growth velocity also showed significant decreases (P<0.001 and P=0.002, respectively). Predicted adult height increased, and the loss in growth potential decreased over time, both with P<0.001.
Interpretation
The findings suggest that leuprorelin acetate microspheres effectively suppress the HPG axis and may increase predicted adult height in early and fast puberty girls. However, the clinical significance of the observed changes, particularly in hormone levels and growth metrics, should be interpreted cautiously due to the lack of a control group and the retrospective nature of the study. These results may not be generalizable beyond the specific population studied.
Key findings
- Median LH decreased from 2.7 (2.23-3.51) mIU/mL at T0 to 0.66 (0.48-1.22) mIU/mL at T4, P<0.001.
- Median FSH decreased from 5.27 (4.82-6.10) mIU/mL at T0 to 2.00 (1.56-2.42) mIU/mL at T4, P<0.001.
- 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, P<0.001.
- BA/CA ratio decreased over time, P<0.001.
- Growth velocity decreased over time, P=0.002.
- Body mass index initially increased after 3 months of treatment, then showed a reducing trend until month 18, P=0.005.
Limitations
- Single-arm, retrospective cohort design.
- No control group for comparison.
- Potential biases in retrospective data collection.
- Limited generalizability due to single-site study.
- Short follow-up duration for assessing long-term effects.