Ann Pediatr Endocrinol Metab.  2019 Jun;24(2):116-123. 10.6065/apem.2019.24.2.116.

Comparing adult height gain and menarcheal age between girls with central precocious puberty treated with gonadotropin-releasing hormone agonist alone and those treated with combined growth hormone therapy

• Kim MS
• Koh HJ
• Lee GY
• Kang DH
• Kim SY

• KMID: 2452088
• DOI: http://doi.org/10.6065/apem.2019.24.2.116

Abstract

PURPOSE
This study aimed to investigate the outcomes of gonadotropin-releasing hormone agonist (GnRHa) therapy with or without growth hormone (GH) therapy for girls with idiopathic central precocious puberty (CPP).
METHODS
The medical records of 166 girls diagnosed with CPP from 2002 to 2017 were retrospectively reviewed. All included patients were treated with GnRHa for ≥36 months. Changes in height standard deviation score (SDS) for bone age, chronological age (CA), and predicted adult height (PAH) were assessed for the first three years of treatment. The final height gain SDS was calculated as the difference between the initial PAH SDS and adult height (AH) SDS; these were then compared between the GnRHa group (group A, n=135) and the combined GnRHa/GH group (group B, n=31).
RESULTS
The initial mean CA was 7.89 years. The mean menarcheal age was 13.12 years (group A, 13.1±0.99; group B, 13.18±0.58 years; P=0.755). PAH SDS at the start of GnRHa treatment and AH SDS were significantly lower in group B than in group A (PAH SDS: -2.20±0.83 vs. -3.19±0.84, P<0.001; AH SDS: 0.18±084 vs. -0.30±0.66, P=0.021). The increase in PAH SDS was higher in group B than in group A for the first three years of GnRHa treatment (1.66±0.66 vs. 2.35±0.93, P<0.001). The height gain SDS was significantly higher in group B than in group A (2.5±0.75 vs. 2.93±1.02, P=0.048). Younger age, higher PAH at the start of treatment, and a greater increase in PAH SDS during the first year of GnRHa treatment positively affected AH.
CONCLUSIONS
The combined GH group had more additional height gain than the GnRHa-alone group.

Keyword

Puberty; Precocious; Gonadotropin-releasing hormone; Growth hormone; Body Height

MeSH Terms

Adolescent
Adult*
Body Height
Female*
Gonadotropin-Releasing Hormone*
Growth Hormone*
Humans
Medical Records
Puberty
Puberty, Precocious*
Retrospective Studies
Gonadotropin-Releasing Hormone
Growth Hormone

Figure

• 

  Fig. 1. Trail design schematic. CPP, central precocious puberty; GnRHa, gonadotropin-releasing hormone agonist; Tx, treatment; AH, adult height; EMR, electronic medical record; GH, growth hormone.

• 

  Fig. 2. Changes in height SDSc (A), height SDSb (B), PAH (C), and PAH SDS (D) of subjects with CPP by type of treatment (black, group A; grey, group B). Group A, GnRHa alone group; group B, combined GnRHa/GH group; SDS, standard deviation score; SDSc, standard deviation score for chronological age; SDSb, standard deviation score for bone age; GnRHa, gonadotropin-releasing hormone agonist; PAH, predicted adult height; Tx, treatment. *P<0.05 vs. 1 year ago. ***P<0.001 vs. 1 year ago.

• 

  Fig. 3. Comparison of PAH, MPH, AH, and changes in subjects with central precocious puberty by type of treatment, expressed as (A) height, (B) SDS, and (C) PAH SDS for the first 3 years of gonadotropin-releasing hormone agonist (GnRHa) treatment. Group A, GnRHa alone group; group B, combined GnRHa/GH group; PAH, predicted adult height; MPH, midparental height; AH, adult height; SDS, standard deviation score. *P<0.001 vs. PAH or PAH SDS at start of GnRHa treatment. ***P<0.001 between the GnRHa group and the GnRHa plus GH group.

Reference

References

1. Partsch CJ, Sippell WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update. 2001; 7:292–302.

2. Su PH, Wang SL, Chen JY, Chen SJ, Ke JC. A study of anthropomorphic and biochemical characteristics in girls with central precocious puberty and thelarche variant. J Pediatr Endocrinol Metab. 2008; 21:213–20.

3. Cesario SK, Hughes LA. Precocious puberty: a comprehensive review of literature. J Obstet Gynecol Neonatal Nurs. 2007; 36:263–74.

4. Chauhan A, Grissom M. Disorders of childhood growth and development: precocious puberty. FP Essent. 2013; 410:25–31.

5. 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.

6. Partsch CJ, Heger S, Sippell WG. Management and outcome of central precocious puberty. Clin Endocrinol (Oxf ). 2002; 56:129–48.

7. Crowley WF Jr, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB Jr. Therapeutic use of pituitary desensitization with a long-acting lhrh agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab. 1981; 52:370–2.

8. Parker KL, Lee PA. Depot leuprolide acetate for treatment of precocious puberty. J Clin Endocrinol Metab. 1989; 69:689–91.

9. Allali S, Lemaire P, Couto-Silva AC, Prété G, Trivin C, Brauner R. Predicting the adult height of girls with central precocious puberty. Med Sci Monit. 2011; 17:PH41–8.

10. Clemons RD, Kappy MS, Stuart TE, Perelman AH, Hoekstra FT. Long-term effectiveness of depot gonadotropin-releasing hormone analogue in the treatment of children with central precocious puberty. Am J Dis Child. 1993; 147:653–7.

11. Kauli R, Galatzer A, Kornreich L, Lazar L, Pertzelan A, Laron Z. Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation of predictions by the Bayley-Pinneau method. Horm Res. 1997; 47:54–61.

12. Lanes R, Soros A, Jakubowicz S. Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin suppressive effect and final height obtained with two different analogs. J Pediatr Endocrinol Metab. 2004; 17:759–66.

13. Léger J, Reynaud R, Czernichow P. Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment? J Pediatr. 2000; 137:819–25.

14. 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.

15. Kwon EB, Lee SJ, Cha M, Kim SY. Changes in the predicted adult height after gonadotropin-releasing hormone agonist treatment in girls with idiopathic true precocious puberty. Ann Pediatr Endocrinol Metab. 2012; 17:160–8.

16. Müller J, Juul A, Andersson AM, Sehested A, Skakkebaek NE. Hormonal changes during GnRH analogue therapy in children with central precocious puberty. J Pediatr Endocrinol Metab. 2000; 13 Suppl 1:739–46.

17. Wu JM, Yu J, Yang Y. Gene expression related to growth axis and gonadal axis in puberty rats. Zhong Xi Yi Jie He Xue Bao. 2003; 1:35–8.

18. Cara JF, Burstein S, Cuttler L, Moll GW Jr, Rosenfield RL. Growth hormone deficiency impedes the rise in plasma insulin-like growth factor I levels associated with precocious puberty. J Pediatr. 1989; 115:64–8.

19. Pasquino AM, Municchi G, Pucarelli I, Segni M, Mancini MA, Troiani S. Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty. J Clin Endocrinol Metab. 1996; 81:948–51.

20. Pasquino AM, Pucarelli I, Segni M, Matrunola M, Cerroni F. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone. J Clin Endocrinol Metab. 1999; 84:449–52.

21. Kohn B, Julius JR, Blethen SL. Combined use of growth hormone and gonadotropin-releasing hormone analogues: the national cooperative growth study experience. Pediatrics. 1999; 104(4 Pt 2):1014–8.

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

23. 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.

24. Korea Centers for Disease Control and Prevention (KCDC); Korean Pediatric Society, Committee for the Development of Growth Standard or Korean Children and Adolescents. 2017 Korean children and adolescents growth standard: commentary for the development of 2017 growth chart [Internet]. Cheongwon: KCDC, Division of Chronic Disease Surveillance;2018. [cited 2018 May 11]. Available from: http://www.cdc.go.kr/CDC/contents/CdcKrContentView.jsp?cid=77683&menuIds=HOME001-MNU1130-MNU2743-MNU2748-MNU2744.

25. Oostdijk W, Drop SL, Odink RJ, Hümmelink R, Partsch CJ, Sippell WG. Long-term results with a slow-release gonadotrophin-releasing hormone agonist in central precocious puberty. Dutch-German Precocious Puberty Study Group. Acta Paediatr Scand Suppl. 1991; 372:39–45.

26. Pucarelli I, Segni M, Ortore M, Arcadi E, Pasquino AM. Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution. J Pediatr Endocrinol Metab. 2003; 16:1005–10.

27. Mul D, Oostdijk W, Waelkens JJ, Drop SL. Final height after treatment of early puberty in short adopted girls with gonadotrophin releasing hormone agonist with or without growth hormone. Clin Endocrinol (Oxf). 2005; 63:185–90.

28. Saggese G, Pasquino AM, Bertelloni S, Baroncelli GI, Battini R, Pucarelli I, et al. Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis. Acta Paediatr. 1995; 84:299–304.

29. Mul D, Oostdijk W, Waelkens JJ, Schulpen TW, Drop SL. Gonadotrophin releasing hormone agonist treatment with or without recombinant human GH in adopted children with early puberty. Clin Endocrinol (Oxf). 2001; 55:121–9.

30. Tuvemo T, Gustafsson J, Proos LA. Growth hormone treatment during suppression of early puberty in adopted girls. Swedish Growth Hormone Advisory Group. Acta Paediatr. 1999; 88:928–32.

31. Jung MK, Song KC, Kwon AR, Chae HW, Kim DH, Kim HS. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone. Ann Pediatr Endocrinol Metab. 2014; 19:214–9.

32. Gyon Y, Yun YJ, Kim YD, Han HS. Age at menarche and near final height after treatment with gonadotropin-releasing hormone agonist alone or combined with growth hormone in Korean girls with central precocious puberty. Clin Pediatr Endocrinol. 2015; 24:175–83.

33. Volta C, Regazzi C, Ndaka J, Vitale R, Bernasconi S. Combined therapy with luteinizing hormone releasing hormone agonist (LHRHa) and growth hormone (GH) in central precocious puberty. Acta Biomed. 2005; 76:73–8.