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Pros and cons of GnRHa treatment for early puberty in girls

Nature Reviews Endocrinology volume 10, pages 352–363 (2014)Cite this article

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Key Points

  • Secular trends in age at pubertal development and the potential influence of environmental factors challenge the standard definitions of precocious puberty and the indications for intervention with gonadotropin-releasing hormone agonists (GnRHa)

  • Treatment with GnRHa can improve adult height in patients who present with precocious puberty at a young age, without having adverse effects

  • Whether GnRHa therapy is beneficial for patients with atypical forms of early puberty not driven by luteinising hormone is unknown

  • Early exposure to estrogen (at <8 years old) might have long-term implications for adult health, such as increasing the risks of developing breast cancer, the metabolic syndrome and type 2 diabetes mellitus

  • Alternative intervention strategies need to be evaluated in girls with early puberty, such as weight loss or therapy with insulin sensitizers

Abstract

The timing of puberty has considerable biological, psychosocial and long-term health implications. Secular trends in age at pubertal development, the effects of obesity and the potential effects of environmental endocrine disruptors challenge the standard definitions of precocious puberty and the indications for intervention with gonadotropin-releasing hormone agonists (GnRHa) in girls with precocious puberty. GnRHa therapy is effective in improving adult height in patients who present with classic central precocious puberty (at <8 years old), without causing adverse effects on body composition, BMD and reproductive function. However, its benefits in patients with atypical forms of early puberty not driven by luteinising hormone are not well defined. The role of GnRHa in these patients and the potential benefits in terms of later growth, psychosocial functioning and long-term risk of adult diseases that are associated with early menarche, such as breast cancer and the metabolic syndrome, have not been established.

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Figure 1: Pathophysiology of early puberty.
Figure 2: Typical treatment with GnRHa.

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Authors and Affiliations

  1. Department of Paediatrics and Wellcome Trust—MRC Institute of Metabolic Science, Box 116, Level 8, Addenbrooke's Hospital, University of Cambridge, Cambridge Biomedical Campus, Hills Road, CB2 0QQ, Cambridge, UK

    Ruben H. Willemsen, Daniela Elleri, Rachel M. Williams & David B. Dunger

  2. MRC Epidemiology Unit, Box 285, University of Cambridge, Cambridge Biomedical Campus, Hills Road, CB2 0QQ, Cambridge, UK

    Ken K. Ong

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R.H.W., K.K.O. and D.B.D. researched data for the article, contributed to discussion of content, wrote the article and reviewed/edited the manuscript before submission. D.E. and R.M.W. researched data for the article, contributed to discussion of content and wrote the article.

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Willemsen, R., Elleri, D., Williams, R. et al. Pros and cons of GnRHa treatment for early puberty in girls. Nat Rev Endocrinol 10, 352–363 (2014). https://doi.org/10.1038/nrendo.2014.40

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