Ann Pediatr Endocrinol Metab.  2024 Jun;29(3):161-166. 10.6065/apem.2346132.066.

Long-term efficacy of a triptorelin 3-month depot in girls with central precocious puberty

• Park KH
• Gwag SH
• Kim YJ
• Chung LY
• Kang E
• Nam HK
• Rhie YJ
• Lee KH

• KMID: 2556672
• DOI: http://doi.org/10.6065/apem.2346132.066

Abstract

Purpose
Three-month gonadotropin-releasing hormone agonists (GnRHas) are expected to achieve better compliance in patients with central precocious puberty (CPP) compared to the monthly formulation. However, 1-month depot remains the dominant choice for conventional treatment worldwide. Our study aimed to investigate the long-term efficacy of a 3-month GnRHa for CPP treatment.
Methods
In this retrospective study, 69 Korean girls with CPP were prescribed either triptorelin pamoate (TP) 3-month depot (n=29) or triptorelin acetate (TA) 1-month depot (n=40) and were followed for 1 year after the end of treatment. Auxological, radiological, and biochemical data were collected every 6 months.
Results
Baseline characteristics were similar between the 2 groups. In the TP 3-month depot group, 27 of 29 patients (93.1%) exhibited suppressed luteinizing hormone level (below 2.5 IU/L) after 6 months of treatment, and this suppression level was reserved until the final injection. The degree of bone age advancement in the TP 3-month depot group decreased from 1.8±0.4 years at the start of treatment to 0.6±0.5 years at 1-year posttreatment. The gain in predicted adult height (PAH) 1 year after the end of treatment was similar between the TP 3-month and TA 1-month depot groups (5.2±3.1 and 5.3±2.4 cm, respectively; p=0.875).
Conclusion
A 3-month depot of triptorelin effectively inhibited gonadal and sex hormones, suppressed bone maturation, and increased PAH. For patient convenience, we suggest a 3-month GnRHa regimen as a promising CPP treatment option.

Keyword

Central precocious puberty; Gonadotropin-releasing hormone; Triptorelin pamoate

Reference

References

1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR; ESPE-LWPES GnRH Analogs Consensus Conference Group, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009; 123:e752–62.

2. Baek JW, Nam HK, Jin D, Oh YJ, Rhie YJ, Lee KH. Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2014; 19:27–31.

3. Kim YJ, Kwon A, Jung MK, Kim KE, Suh J, Chae HW, et al. Incidence and prevalence of central precocious puberty in Korea: an epidemiologic study based on a national database. J Pediatr. 2019; 208:221–8.

4. Comite F, Cutler GB, Rivier J, Vale WW, Loriaux DL, Crowley WF. Short-term treatment of idiopathic precocious puberty with a long-acting analog of luteinizing-hormonereleasing hormone - a preliminary-report. New Engl J Med. 1981; 305:1546–50.

5. Swerdloff RS, Heber D. Superactive gonadotropin-releasing hormone agonists. Annu Rev Med. 1983; 34:491–500.

6. Heger S, Muller M, Ranke M, Schwarz HP, Waldhauser F, Partsch CJ, et al. Long-term GnRH agonist treatment for female central precocious puberty does not impair reproductive function. Mol Cell Endocrinol. 2006; 254-255:217–20.

7. Lazar L, Padoa A, Phillip M. Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity. J Clin Endocrinol Metab. 2007; 92:3483–9.

8. 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.

9. Martinez-Aguayo A, Hernandez MI, Beas F, Iniguez G, Avila A, Sovino H, et al. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Met. 2006; 19:963–70.

10. Carel JC, Blumberg J, Seymour C, Adamsbaum C, Lahlou N; Triptorelin 3-month CPP Study Group. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol. 2006; 154:119–24.

11. Jeon MJ, Choe JW, Chung HR, Kim JH. Short-term efficacy of 1-month and 3-month gonadotropin-releasing hormone agonist depots in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2021; 26:171–7.

12. Yang JM, Song QJ, Gao S, Gao YY, Shang XH, Li GM, 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.

13. 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.

14. Bertelloni S, Massart F, Einaudi S, Wasniewska M, Miccoli M, Baroncelli GI. Central precocious puberty: adult height in girls treated with quarterly or monthly gonadotropinreleasing hormone analog triptorelin. Horm Res Paediatr. 2015; 84:396–400.

15. Vatopoulou A, Roos E, Daniilidis A, Dinas K. Long-term effects of treatment of central precocious puberty with gonadotropin-releasing hormone analogs every three months. Gynecol Endocrinol. 2020; 36:1124–6.

16. Lasorella S, Porto R, Iezzi ML, Pistone C, Marseglia GL, Verrotti A, et al. Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of central precocious puberty (CPP): a retrospective study. Gynecol Endocrinol. 2020; 36:338–40.

17. Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr. 1995; 127:47–52.

18. Kim YM, Choi JH, Lee BH, Yoo HW. Efficacy of a single luteinizing hormone measurement after GnRH agonist administration for therapeutic monitoring of girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2012; 17:153–9.

19. Greulich WW, Pyle SI. Radiologic atlas of skeletal development of the hand and wrist. Redwood City (CA): Stanford University Press;1959.

20. 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.

21. Bhatia S, Neely EK, Wilson DM. Serum luteinizing hormone rises within minutes after depot leuprolide injection: implications for mo nitoring therapy. Pediatrics. 2002; 109:E30.

22. Lee HS, Yoon JS, Hwang JS. Luteinizing hormone secretion during gonadotropin-releasing hormone stimulation tests in obese girls with central precocious puberty. J Clin Res Pediatr Endocrinol. 2016; 8:392–8.

23. Fu JF, Liang JF, Zhou XL, Prasad HC, Jin JH, Dong GP, et al. Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty. Obesity. 2015; 23:637–43.

24. Fuld K, Chi C, Neely EK. A randomized trial of 1-and 3-month depot leuprolide doses in the treatment of central precocious puberty. J Pediatr. 2011; 159:982–7. e1.

25. Guaraldi F, Beccuti G, Gori D, Ghizzoni L. Long-term outcomes of the treatment of central precocious puberty. Eur J Endocrinol. 2016; 174:R79–87.

26. Brauner R, Adan L, Malandry F, Zantleifer D. Adult height in girls with idiopathic true precocious puberty. J Clin Endocrinol Metab. 1994; 79:415–20.

27. Oostdijk W, Rikken B, Schreuder S, Otten B, Odink R, Rouwe C, et al. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child. 1996; 75:292–7.

28. Arrigo T, Cisternino M, Galluzzi F, Bertelloni S, Pasquino AM, Antoniazzi F, et al. Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. Eur J Endocrinol. 1999; 141:140–4.

29. Klein KO, Barnes KM, Jones JV, Feuillan PP, Cutler GB Jr. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J Clin Endocrinol Metab. 2001; 86:4711–6.