Ann Pediatr Endocrinol Metab.  2023 Dec;28(4):283-288. 10.6065/apem.2244210.105.

Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty

• Jang S
• Kim SJ
• Lee M
• Lee HI
• Kwon A
• Suh J
• Song K
• Chae HW
• Kim HS

• KMID: 2549321
• DOI: http://doi.org/10.6065/apem.2244210.105

Abstract

Purpose
There are no definite guidelines on the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for treatment of central precocious puberty (CPP). We compared growth outcomes of GnRH agonist at different dosages in girls with idiopathic CPP to assess the optimal dosage.
Methods
This retrospective study included 86 girls with idiopathic CPP who had been treated with GnRH agonist for at least one year and had attained their final adult height. Leuprolide was given as fixed dosage (3.75 mg every 4 weeks in body weight >20 kg, n=72) or weight-based dosage (60–85 μg/kg every 4 weeks, n=14). We compared suppression of advanced puberty and treatment response between the 2 groups.
Results
Peak estradiol and luteinizing hormone and bone age (BA)/chronological age after injection of GnRH agonist were effectively suppressed in both groups. In both groups, the height standard deviation score (SDS) for BA increased after treatment. Final adult height (FAH) (fixed dosage group,160.8±4.1 cm and weight-based dosage group, 161.2±4.4 cm) was significantly higher than the initial predicted adult height (PAH) (155.5±3.3 and 156.1±3.6 cm, respectively) (both P<0.001) and similar to midparental height (159.8±3.3 and 160.6±3.7 cm, respectively). There were no differences in gain in height SDS for BA and gain in height (FAH-PAH at the start) between the 2 groups.
Conclusion
There were no differences in treatment outcome between fixed dosage (3.75 mg/4 wk) and weight-based dosage (60–85 μg/kg/4wk) of GnRH agonist. Therefore, a fixed dosage of GnRH agonist can be used more conveniently for CPP treatment without growth oversuppression.

Keyword

Gonadotropin-releasing hormone agonist; Administration and dosage; Precocious puberty; Treatment outcome

Figure

• 

  Fig. 1. Changes in height SDS for bone age during treatment in 86 CPP patients treated with GnRH agonist. SDS, standard deviation score; CPP, central precocious puberty; GnRH, gonadotropin-releasing hormone; GnRHa, GnRH agonist. *P<0.05 versus values at the start of GnRHa.

• 

  Fig. 2. Initial predicted adult height, midparental height, and final adult height in 86 CPP patients treated with GnRH agonist at different dosages. PAH, predicted adult height; MPH, midparental height; FAH, final adult height. *P<0.05 versus values of initial PAH.

Reference

References

1. Styne DM, Grumbach MM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In : Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 12th ed. Philadelphia (PA): Saunders Elsevier;2011. p. 1054–201.

2. Kim YJ, Kwon AR, Jung MK, Kim KE, Suh JH, 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.

3. De Sanctis V, Corrias A, Rizzo V, Bertelloni S, Urso L, Galluzzi F, et al. Etiology of central precocious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty. J Pediatr Endocrinol Metab. 2000; 13 Suppl 1:687–93.

4. Cisternino M, Arrigo T, Pasquino AM, Tinelli C, Antoniazzi F, Beduschi L. Etiology and age incidence of precocious puberty in girls: a multicentric study. J Pediatr Endocrinol Metab. 2000; 13 Suppl 1:695–701.

5. Huynh QTV, Ho BT, Le NQK, Trinh TH, Lam LHT, Nguyen NTK, et al. Pathological brain lesions in girls with central precocious puberty at initial diagnosis in Southern Vietnam. Ann Pediatr Endocrinol Metab. 2022; 27:105–12.

6. Carel JC, Léger J. Clinical practice. Precocious puberty. N Engl J Med. 2008; 358:2366–77.

7. Bangalore Krishna K, Fuqua JS, Rogol AD, Klein KO, Popovic J, Houk CP, et al. Use of gonadotropin-releasing hormone analogs in children: update by an International Consortium. Horm Res Paediatr. 2019; 91:357–72.

8. Kim HS. Clinical application of gonadotropin-releasing hormone analogs in children and adolescents. Korean J Pediatr. 2010; 53:294–9.

9. 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.

10. Vurallı D, Alikaşifoğlu A, İyigün I, Canoruç D, Ozon A, Gönç N, et al. Treatment with depot leuprolide acetate in girls with idiopathic precocious puberty: what parameter should be used in deciding on the initial dose? J Clin Res Pediatr Endocrinol. 2020; 12:37–44.

11. Lee PA, Neely EK, Fuqua J, Yang D, Larsen LM, Mattia-Goldberg C, et al. Efficacy of leuprolide acetate 1-month depot for central precocious puberty (CPP): growth outcomes during a prospective, longitudinal study. Int J Pediatr Endocrinol. 2011; 2011:7.

12. 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.

13. Tanaka T, Hibi I, Kato K, Saito S, Shimizu N, Suwa S, et al. A dose finding study of a super long-acting luteinizing hormone-releasing hormone analog (leuprolide acetate depot, TAP-144-SR) in the treatment of central precocious puberty. The TAP-144-SR CPP Study Group. Endocrinol Jpn. 1991; 38:369–76.

14. Shim KS, Bae CW, Yang YJ. A comparative study of the puberty suppression effect of gonadotropin-releasing hormone agonist in precocious or early puberty girls. Korean J Pediatr. 2008; 51:634–9.

15. Jin HY, Choi JH, Yoo HW. Evaluation of efficacy of GnRH agonist on predicted adult height (PAH) in patients with central precocious puberty using two different dosages. J Korean Soc Pediatr Endocrinol. 2010; 15:120–5.

16. Ab Rahim SN, Omar J, Tuan Ismail TS. Gonadotropin-releasing hormone stimulation test and diagnostic cutoff in precocious puberty: a mini review. Ann Pediatr Endocrinol Metab. 2020; 25:152–5.

17. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 2nd edition. Stanford: Stanford University Press;1959.

18. 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.

19. Korea Center for Disease Control and Prevention; The Korean Pediatric Society; The Committee for the Development of Growth Standard for Korean Children and Adolescents. 2007 Korean children and adolescents growth standard (commentary for the development of 2007 growth chart). Seoul (Korea): Division of Chronic Disease Surveillance;2007.