ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Horm Res Paediatr. 2018;90(1):1–7.

The authors discuss why GnRH analog therapies should not be used in all girls with central precocious puberty (CPP), but only in those cases where the predicted benefits outweigh the risks and high cost of the treatment.

Epidemiological studies in Europe and USA show declining average age at onset of puberty (1). Consequently, an increasing proportion of girls are categorized as ‘precocious’, according to the widely accepted definition of CPP. GnRH analog treatment is used to suppress the hypothalamic-pituitary-gonadal axis in girls with CPP, in order to: a) slow the rate of skeletal maturation and thus increase predicted adult height (2); b) reduce the distress of early physical changes and menarche (3). The authors argue that this treatment is very long (2–4 years) and expensive ($20,000–30,000 per year). They analyze the existing data on the benefits of CPP treatment: 1) do GnRH analogs increase average height in children with CPP? 2) do girls with CPP have more psychological problems than prepubertal girls at the same age?

Studies show that the greatest height gain from GnRH analog treatment occurs in girls with onset of puberty <6 years old (4–7). The decision to initiate therapy in girls with onset at 6–8 years old should be individualized (8), especially in most of these girls who have slowly progressive CPP and will achieve target range adult heights without treatment (9).

It remains unclear whether psychosocial stress should be considered a predictable consequence of early puberty supporting a decision to start GnRHa treatment (10), and if so, whether treatment relieves such stress (11).

Thus, the decision regarding GnRHa therapies should attempt to balance benefits, risks and costs for each child individually and should be decided after an informed discussion with the family.

References: 1. Sorensen K, Mouritsen A, Aksglaede L, Hagen CP, Mogensen SS, Juul A. 2012 Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty. Horm Res Paediatr. 77: 137–45.

2. Comite F, Cassorla F, Barnes KM, Hench KD, Dwyer A, Skerda MC, Loriaux DL, Cutler GB Jr, Pescovitz OH. 1986 Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicted height. JAMA 255: 2613–6.

3. Sonis WA, Coite F, Bleu J, Pescovitz OH, Rahn CW, Hench KD, Cutler GB Jr, Loriaux DL, Klein RP. 1985 Behavior problem and social competence in girls with true precocious puberty. J Pediatr. 106: 156–60.

4. Paul D, Conte FA, Grumbach MM, Kaplan SL. 1995 Long-term effect of gonadotropin-releasing hormone agonist therapy on final and near-final height in 26 children with true precocious puberty treated at a median age of less than 5 years. J Clin Endocrinol Metab. 80(2): 546–51.

5. Cassio A, Cacciari E, Balsamo A, Bal M, Tassinari D. 1999 Randomised trial ogf LHRH analogue treatment on final heigh in girls with onset of puberty aged 7.5–8.5 years. Arch Dis Child. 81(4): 329–32.

6. Pasquino AM, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. 2008 Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing analogs: impact on adult height, body mass index, bone mineral content, and reproductive function. J Clin Endocrinol Metab. 93: 190–5.

7. Bereket A. 2017 A crItical appraisal of the effect of gonadotropin-releasing hormone analog treatment on adult height of girls with central precocious puberty. J Clin Endocrinol. Metab. Suppl 2:33–48.

8. Carel JC, Eugster EA, Rogol A, Chizzoni L, Palmert MR, Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM. ESPE-LWPES GnRH Analogs Concensus Conference Group. 2009 Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Prediatrics. 123(4):e752–62.

9. Massart F, Federico G, Harrell JC, Saggese G. 2009 Growth outcome during GnRH agonist treatments for slowly preogressive central precocious puberty. Neuroendocrinology. 90: 307–14.

10. Schoelwer MJ, Donahue KL, Didrick P, Eugster EA. 2017 One-year follow-up of girls with precocious puberty and their mothers: do psychological assessments change over time or with treatment? Horm Res Paediatr. 88: 347–53.

11. Wojniusz S, Callens N, Sütterlin S, Andersson S, De Schepper J, Gies I, Vanbesien J, De Waele K, Van Aken S, Craen M, Vögele C, Cools M, Haraldsen IR. 2017 Cognitive, emotional, and psychosocial functioning of girls treated with pharmacological puberty block-age for idiopathic central precocious puberty. Front Psychol. 7: 1053