Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study

Siqi Huang; Lina Zhang; Chenchen Gao; Hui Ou; Lele Hou; Zulin Liu; Dilong Wang; Yingying Xu; Liyang Liang; Zhe Meng

doi:10.1515/jpem-2023-0410

Article

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study

Siqi Huang , Lina Zhang , Chenchen Gao , Hui Ou , Lele Hou , Zulin Liu , Dilong Wang , Yingying Xu , Liyang Liang and Zhe Meng

Published/Copyright: November 20, 2023

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 1

Abstract

Objectives

This study aimed to evaluate the efficacy and safety of 3-month leuprorelin acetate (3-month LA, 11.25 mg) for the treatment of idiopathic central precocious puberty (ICPP) in Chinese girls.

Methods

We conducted a single-center retrospective study in China on 28 girls with ICPP who received at least one year of 3-month LA treatment. Data from anthropometry, biochemistry, bone age (BA), and pelvic ultrasonography were assessed before and every 6 months during medication.

Results

At CPP diagnosis, the mean chronological age (CA) was 7.8±0.8 years, with bone age advancement (BA–CA) of 1.5±0.8 years. After treatment initiation, growth velocity decreased significantly from 8.5±1.6 cm/year to 5.8±1.1 cm/year at month 12 (p<0.001). GnRH-stimulated peak LH ≤3IU/L, the primary efficacy criterion, was observed in 27 out of 28 (96.4 %) children at month 3. Basal estradiol <20 pg/mL was achieved by all 28 girls (100 %) at month 6 and remained stable at month 12. Basal follicle-stimulating hormone (FSH) decreased from 4.1±3.5 to 1.7±0.9 (p<0.001), and basal LH was also significantly reduced from 3.3±6.5 to 0.7±0.8 (p=0.035) at month 12. The mean predicted adult height (PAH) at treatment initiation was 152.7±5.8 cm, it increased significantly to 157.5±5.5 cm (p=0.007) after one-year treatment. Pubertal development was slowed in most patients, and in some cases, it was even reversed. Only one patient (3.6 %) reported local intolerance.

Conclusions

Three-month leuprorelin acetate is a safe and effective treatment for suppressing the pituitary–gonadal axis and restoring impaired adult height in Chinese girls.

Keywords: central precocious puberty; therapy; predicted adult height; tolerance; GnRHa

Corresponding authors: Liyang Liang and Zhe Meng, Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, E-mail: liangliy@mail.sysu.edu.cn, mengzhe@mail.sysu.edu.cn

Siqi Huang and Lina Zhang should be considered joint first author.

Acknowledgments

We are grateful to the patients for the participation in this study.

Research ethics: This retrospective study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital and was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Informed consent: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Latronico, AC, Brito, VN, Carel, JC. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol 2016;4:265–74. https://doi.org/10.1016/s2213-8587(15)00380-0.Search in Google Scholar

2. Carel, JC, Léger, J. Clinical practice. Precocious puberty. N Engl J Med 2008;358:2366–77. https://doi.org/10.1056/nejmcp0800459.Search in Google Scholar PubMed

3. Bangalore Krishna, K, Fuqua, JS, Rogol, AD, Klein, K, Popovic, J, Houk, C, et al.. Use of gonadotropinreleasing hormone analogs in children: update by an international consortium. Horm Res Paediatr 2019;91:357–72. https://doi.org/10.1159/000501336.Search in Google Scholar PubMed

4. Carel, JC, Lahlou, N, Jaramillo, O, Montauban, V, Teinturier, C, Colle, M, et al.. Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg). J Clin Endocrinol Metab 2002;87:4111–16. https://doi.org/10.1210/jc.2001-020243.Search in Google Scholar PubMed

5. Lee, PA, Klein, K, Mauras, N, Neely, EK, Bloch, CA, Larsen, L, et al.. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J Clin Endocrinol Metab 2012;97:1572–80. https://doi.org/10.1210/jc.2011-2704.Search in Google Scholar PubMed

6. Badaru, A, Wilson, DM, Bachrach, LK, Fechner, P, Gandrud, LM, Durham, E, et al.. Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty. J Clin Endocrinol Metab 2006;91:1862–7. https://doi.org/10.1210/jc.2005-1500.Search in Google Scholar PubMed

7. Lee, PA, Klein, K, Mauras, N, Lev-Vaisler, T, Bacher, P. 36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab 2014;99:3153–9. https://doi.org/10.1210/jc.2013-4471.Search in Google Scholar PubMed

8. Mericq, V, Lammoglia, JJ, Unanue, N, Villaroel, C, Hernández, MI, Avila, A, et al.. Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results. Clin Endocrinol 2009;71:686–90. https://doi.org/10.1111/j.1365-2265.2009.03584.x.Search in Google Scholar PubMed

9. Chung, LY, Kang, E, Nam, HK, Rhie, YJ, Lee, KH. Efficacy of triptorelin 3-month depot compared to 1-month depot for the treatment of Korean girls with central precocious puberty in single tertiary center. J Korean Med Sci 2021;36:e219. https://doi.org/10.3346/jkms.2021.36.e219.Search in Google Scholar PubMed PubMed Central

10. Li, WJ, Gong, CX, Guo, MJ, Xing, J, Li, T, Song, WH, et al.. Efficacy and safety of domestic leuprorelin in girls with idiopathic central precocious puberty: a multicenter, randomized, parallel, controlled trial. Chin Med J 2015;128:1314–20. https://doi.org/10.4103/0366-6999.156773.Search in Google Scholar PubMed PubMed Central

11. Luo, X, Hou, L, Zhong, Y, You, C, Yang, Y, Wu, X, et al.. An open label, multicenter clinical trial that investigated the efficacy and safety of leuprorelin treatment of central precocious puberty in Chinese children. Medicine 2021;100:e28158. https://doi.org/10.1097/md.0000000000028158.Search in Google Scholar PubMed PubMed Central

12. Wang, L, Jiang, Q, Wang, M, Xu, J, Jin, J. The effect of triptorelin and leuprolide on the level of sex hormones in girls with central precocious puberty and its clinical efficacy analysis. Transl Pediatr 2021;10:2307–12. https://doi.org/10.21037/tp-21-352.Search in Google Scholar PubMed PubMed Central

13. Lin, YC, Lin, CY, Chee, SY, Yen, HR, Tsai, FJ, Chen, CY, et al.. Improved final predicted height with the injection of leuprolide in children with earlier puberty: a retrospective cohort study. PLoS One 2017;12:e0185080. https://doi.org/10.1371/journal.pone.0185080.Search in Google Scholar PubMed PubMed Central

14. Yang, J, Song, Q, Gao, S, Gao, Y, Shang, X, Li, G, et al.. Efficacy of leuprorelin 3-month depot (11.25 mg) compared to 1-month depot (3.75 mg) for central precocious puberty in Chinese girls: a prospective cohort study. Int J Endocrinol 2022;2022:1043293. https://doi.org/10.1155/2022/1043293.Search in Google Scholar PubMed PubMed Central

15. The Subspecialty Group of Endocrinological, Hereditary and Metabolic Disease, the Society of Pediatrics, Chinese Medical Association, Editorial Board of the Chinese Journal of Pediatrics. Consensus on diagnosis and treatment of central precocious puberty. Zhonghua Er Ke Za Zhi 2015;53:412–18.Search in Google Scholar

16. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303. https://doi.org/10.1136/adc.44.235.291.Search in Google Scholar PubMed PubMed Central

17. Bayley, N, Pinneau, SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich–Pyle hand standards. J Pediatr 1952;40:423–41. https://doi.org/10.1016/s0022-3476(52)80205-7.Search in Google Scholar PubMed

18. Liji, HCY, Zong, XN, Zhang, YQ. China Body mass index growth curves for Chinese children and adolescents aged 0 to 18 years. Zhonghua Er Ke Za Zhi 2009;47:493–8.Search in Google Scholar

19. Coordinating Study Group of Nine Cities on the Physical Growth and Development of Children, Capital Institute of Pediatrics. A national survey on growth of children under 7 years of age in nine cities of China, 2005. Zhonghua Er Ke Za Zhi 2009;45:609-14.Search in Google Scholar

20. Carel, JC, Lahlou, N, Guazzarotti, L, Joubert-Collin, M, Roger, M, Colle, M, et al.. Treatment of central precocious puberty with depot leuprolide acetate. French Leuprorelin Trial Group. Eur J Endocrinol 1995;132:699–704. https://doi.org/10.1530/eje.0.1320699.Search in Google Scholar PubMed

21. The Subspecialty Group of Endocrinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association; the Editorial Board, Chinese Journal of Pediatrics. Expert consensus on the diagnosis and treatment of central precocious puberty (2022). Zhonghua Er Ke Za Zhi 2023;61:16–22. https://doi.org/10.3760/cma.j.cn112140-20220802-00693.Search in Google Scholar PubMed

22. Ramos, CO, Canton, APM, Seraphim, CE, Faria, AG, Tinano, FR, Mendonca, BB, et al.. Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg). J Pediatr Endocrinol Metab 2021;34:1371–7. https://doi.org/10.1515/jpem-2021-0142.Search in Google Scholar PubMed

23. Traggiai, C, Perucchin, PP, Zerbini, K, Gastaldi, R, De Biasio, P, Lorini, R. Outcome after depot gonadotrophin-releasing hormone agonist treatment for central precocious puberty: effects on body mass index and final height. Eur J Endocrinol 2005;153:463–4. https://doi.org/10.1530/eje.1.01975.Search in Google Scholar PubMed

24. Vuralli, D, Ozon, ZA, Gonc, EN, Alikasifoglu, A, Kandemir, N. Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty. J Pediatr Endocrinol Metab 2020;33:99–105. https://doi.org/10.1515/jpem-2019-0214.Search in Google Scholar PubMed

25. Censani, M, Feuer, A, Orton, S, Askin, G, Vogiatzi, M. Changes in body mass index in children on gonadotropin-releasing hormone agonist therapy with precocious puberty, early puberty or short stature. J Pediatr Endocrinol Metab 2019;32:1065–70. https://doi.org/10.1515/jpem-2019-0105.Search in Google Scholar PubMed

26. Paterson, WF, McNeill, E, Young, D, Donaldson, MD. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol 2004;61:626–34. https://doi.org/10.1111/j.1365-2265.2004.02146.x.Search in Google Scholar PubMed

27. Bertelloni, S, Baroncelli, GI, Ferdeghini, M, Menchini-Fabris, F, Saggese, G. Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues. Eur J Pediatr 2000;159:369–74. https://doi.org/10.1007/s004310051289.Search in Google Scholar PubMed

Received: 2023-09-13

Accepted: 2023-10-30

Published Online: 2023-11-20

Published in Print: 2024-01-29

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0410

Keywords for this article

central precocious puberty; therapy; predicted adult height; tolerance; GnRHa

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study

Article

Abstract

Objectives

Methods

Results

Conclusions

Acknowledgments

References

Articles in the same Issue

Articles in the same Issue

Articles in the same Issue

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study