Central precocious puberty: assessment, diagnosis and decisions about treatment
Intended for healthcare professionals
Evidence and practice    

Central precocious puberty: assessment, diagnosis and decisions about treatment

Leah Mason Endocrine nurse specialist, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, England
Nikolaos Daskas Consultant paediatric endocrinologist, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, England

Why you should read this article:
  • To understand the long-term negative physical and psychosocial consequences of precocious puberty

  • To learn about central precocious puberty (CPP), the more prevalent form of precocious puberty

  • To familiarise yourself with the factors to consider when deciding whether to treat CPP

Precocious puberty is defined as the onset of puberty before the age of eight years in girls and before the age of nine years in boys. It is associated with negative physical health consequences in the long term and can also have negative psychosocial effects, particularly in adolescence. Central precocious puberty (CPP), which is caused by the early activation of the hypothalamic-pituitary-gonadal axis, is the more prevalent form of precocious puberty.

This article explains CPP and its signs, assessment, diagnosis and treatment. It also discusses the factors to consider when deciding whether or not to treat it, stressing the importance of a shared decision-making process that children and parents should be involved in. Precocious puberty must be diagnosed and managed by specialists, but all children’s nurses need a broad understanding of the condition so that they can refer children as early as possible and reassure and advise families.

Nursing Children and Young People. doi: 10.7748/ncyp.2024.e1492

Peer review

This article has been subject to open peer review and checked for plagiarism using automated software

Correspondence

leah.mason@ouh.nhs.uk

Conflict of interest

None declared

Mason L, Daskas N (2024) Central precocious puberty: assessment, diagnosis and decisions about treatment. Nursing Children and Young People. doi: 10.7748/ncyp.2024.e1492

Published online: 08 January 2024

Precocious puberty is defined in girls as showing signs of puberty before the age of eight years and in boys as showing signs of puberty before the age of nine years (Latronico et al 2016). Increasing numbers of children are diagnosed with precocious puberty every year worldwide (Roberts 2016).

Abnormal timing of puberty, whether it occurs earlier or later than normal, has substantial biological, psychosocial and long-term health implications (Day et al 2015, Alotaibi 2019). For example, early puberty starting at the age of eight or nine has been found to be associated with higher risks of angina, hypertension and type 2 diabetes (Day et at 2015), while precocious puberty has been shown to be associated with smaller adult height and loss of fertility (Luo et al 2021). Johansson and Ritzén (2005) and Copeland et al (2010), who conducted studies in girls who had undergone normal early puberty (as opposed to precocious puberty), found that early maturing girls displayed higher levels of self-reported criminality, substance use, social isolation, early sexual behaviour and psychological problems during adolescence but that most of these differences had attenuated by the time they had reached young adulthood.

The diagnosis and management of precocious puberty requires the involvement of specialists such as endocrine nurses and paediatric endocrinologists, but it is important that all children’s nurses know the signs of precocious puberty so that they can refer children for assessment as early as possible. It is equally important that children’s nurses have a broad understanding of the condition, its assessment and treatment – including the decision-making required about treatment – so that they can reassure and advise families whose child is being referred for specialist assessment.

Precocious puberty

Precocious puberty is characterised by the early development of secondary sexual characteristics, early accelerating growth and early advancing bone maturation. The age of onset of precocious puberty in affected children varies (Carel and Léger 2008, Spaziani et al 2021).

There are two forms of precocious puberty (Mushtaq and Howard 2023):

  • Central precocious puberty (CPP), also called gonadotrophin-dependent precocious puberty, which is caused by the early activation of the hypothalamic-pituitary-gonadal axis.

  • Gonadotrophin-independent precocious puberty (GIPP), which is caused by the autonomous secretion of sex hormones.

CPP is the more prevalent form of precocious puberty, while GIPP is rare (Fuqua 2013); therefore, this article focuses on CPP.

The hypothalamic-pituitary-gonadal axis is well developed at birth and a ‘mini puberty’ occurs between birth and the age of 6-9 months (Guimiot et al 2012, Orlowski and Sarao 2023). At that age, there is a physiological resistance to the action of sex hormones, so secondary sex characteristics do not develop. The hypothalamic-pituitary-gonadal axis then enters a period of quiescence and reactivates at the onset of puberty (Alotaibi 2019, Spaziani et al 2021). It is unclear why the hypothalamic-pituitary-gonadal axis sometimes reactivates early.

CPP can be caused by cerebral malformations and lesions in the brain (Latronico et al 2016), but this is rare and CPP is idiopathic in up to 90% of cases in girls (Carel and Léger 2008). Some researchers have shown that CPP can occur in children who have a family history of early puberty, which suggests that genetic factors are implicated (Zacharin et al 2013). Body fat mass and ethnic background are further factors that can bring forward the onset of puberty: children from African ethnic backgrounds and children who are obese, especially girls, are more likely to develop signs of puberty early (Muir 2006, Homaei et al 2021, Brito et al 2023).

Assessment and diagnosis

Precocious puberty is suspected when children begin to show pubertal characteristics at an earlier age than expected. Signs of CPP include accelerating growth, advancing bone maturation, and growth of pubic hair before the age of eight years in girls and nine years in boys; in girls, the development of breasts will also be seen (Fuqua 2013, Latronico et al 2016).

Assessment should be conducted by a healthcare professional with specialist knowledge and experience – such as an endocrine nurse or a paediatric endocrinologist – who is familiar with the Tanner staging method (a classification tool that documents the development of secondary sex characteristics during puberty) (Tanner and Whitehouse 1976, Roberts 2016) and other available diagnostic tools. Self-assessment by families and assessment by non-specialists can lead to misdiagnosis (Desmangles et al 2006).

Diagnostic investigations usually include:

  • An assessment of growth rate.

  • An assessment of bone age.

  • An assessment of pubertal development.

  • A blood test to measure the levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH) in the blood.

  • A stimulation test to measure LH and FSH levels after an injection of gonadotrophin-releasing hormone (GnRH).

Growth rate and bone age

During assessment, the child’s height is compared with their parental centiles. A mid-parental height (the average adult height expected for children born from a set of parents) can be calculated using the final height of each parent and taking into consideration that males will grow an extra 13cm on average than females (Binder et al 2021). This mid-parental height can help determine whether a child is growing outside the expected range and/or at an increased rate. An X-ray of the child’s hand is taken to stage bone maturation, determine the child’s bone age (by the stage of maturation) and compare it with their chronological age (Donaldson et al 2019). In children with CPP, bone age is expected to be advanced of chronological age unless the onset of CPP is relatively recent (Pinhas-Hamiel et al 2014).

Pubertal development

Pubertal development is assessed against the Tanner stages (Roberts 2016), which range from pre-pubertal (stage I) to adult (stage V). The assessment encompasses an examination of axillary hair and pubic hair development in boys and girls, breast development in girls and external genitalia development in boys (Marshall and Tanner 1969, Tanner and Whitehouse 1976). Tanner stages in males and females are shown in Figure 1 and Figure 2, respectively. However, Tanner stages can be misleading because of thelarche and adrenarche, two physiological stages of sexual maturation that can start before puberty. Thelarche, or breast budding, is the stage at which female breasts start developing (Muir 2006). Premature thelarche, which is potentially due to increased sensitivity to hormones, has not been shown to affect growth or the timing of puberty. Adrenarche is the stage at which the adrenal glands start producing increasing levels of androgens, which prompts the development of pubic hair and axillary hair, body odour and sexual attraction, and can cause skin oiliness, mild acne and mood swings. Adrenarche may start up to two years before puberty, often between the ages of six years and nine years (Jee et al 2023). When assessing pubertal development, it is important to distinguish between thelarche and adrenarche, which do not require treatment, and precocious puberty, which may require treatment (Kaplowitz 2021).

Figure 1.

Tanner stages: external genitalia and pubic hair development in males

ncyp.2024.e1492_0001.jpg
Figure 2.

Tanner stages: breast development and pubic hair development in females

ncyp.2024.e1492_0002.jpg

Key points

  • Precocious puberty is defined in girls as signs of puberty showing before the age of eight years and in boys as signs of puberty showing before the age of nine years

  • Precocious puberty is characterised by the early development of secondary sexual characteristics, early accelerating growth and early advancing bone maturation

  • Assessment should be conducted by a healthcare professional with specialist knowledge and experience – such as an endocrine nurse or a paediatric endocrinologist

  • In the UK, an intramuscular injection of gonadotrophin-releasing hormone agonists given every one, three or six months is the gold-standard treatment for central precocious puberty

In boys, the volume of the testes is also measured using a Prader orchidometer, a physical object composed of 12 beads increasing in size from 1mL to 25mL – three for pre-puberty, six for puberty and three for post-puberty (Kvernebo Sunnergren et al 2023).

Blood tests and stimulation tests

Thorough assessments of growth rate, bone age and pubertal development can reduce the need for blood tests and stimulation tests (Kaplowitz 2021). However, these tests are often needed to reach a definitive diagnosis.

A blood test is conducted to measure the levels of LH and FSH in the blood. These hormones are naturally present at low levels and elevated levels potentially indicate that CPP is present. However, if the levels of LH and FSH are not elevated, CPP cannot be ruled out because of the fluctuations in the release of these hormones and a stimulation test will be required to diagnose CPP (Pereira 2023).

A stimulation test consists of injecting GnRH to stimulate the pituitary gland to release LH and FSH. One blood sample is taken before the injection to determine the child’s normal levels of LH and FSH. Two further blood samples are taken 20 minutes and 60 minutes after the injection to measure LH and FSH levels again. If LH and FSH levels are raised at these two time points, this indicates that the pubertal axis (the hypothalamic-pituitary-gonadal axis) is active and therefore that CPP is present (Vurallı et al 2020).

Researchers are exploring ways of diagnosing CPP without the need for blood tests. In girls, one alternative is to undertake a pelvic ultrasound to assess the internal genitalia, since the volume of the ovaries and uterine body has been shown to be the most reliable factor for diagnosing CPP (Yu et al 2019a). However, this form of testing is expensive and requires input from specialists, so it is not widely used. Researchers are also evaluating the effectiveness of urinary LH levels as a diagnostic marker (Brambilla et al 2023).

Treatment

In the UK, an intramuscular injection of GnRH agonists every one, three or six months is the gold-standard treatment for CPP (Eugster 2019). GnRH agonists are synthetic peptide drugs designed to interact with the GnRH receptor, leading to desensitisation and therefore suppression of the production of LH and FSH (Lahlou et al 2000). Treatment results in the stabilisation, and sometimes regression, of pubertal signs (Carel et al 2009). The earlier treatment is started, the more effective it is, with minimal benefits in children who start treatment after the age of eight years (Pereira 2023). It must be noted, however, that although treatment with GnRH agonists is widely used to treat CPP, the results of research into its use are still conflicting (Bangalore Krishna et al 2019).

The decision to treat or not to treat should be made on an individual basis. In many affected children, CPP progresses slowly and is therefore unlikely to warrant treatment (Kaplowitz 2021). A 3-6-month period of observation is advisable before making a treatment decision, to check how quickly CPP is progressing and whether treatment is needed (Kaplowitz 2021). Further aspects to consider when deciding whether or not to treat CPP are outlined in the next section of this article.

Once treatment starts, monitoring is required to check whether treatment is suppressing the production of LH and FSH. Monitoring usually involves regularly reassessing the child’s growth rate, bone age and pubertal development as well as conducting further blood tests and stimulation tests. In future, it may be possible to monitor the effectiveness of treatment by measuring urinary LH levels (Yüce et al 2020). Complications and side-effects of treatment include headaches, hot flushes, depression and a higher risk of polycystic ovary syndrome in girls (Tonini and Lazzerini 2000, Fuqua 2013). In terms of outcomes after treatment with GnRH agonists, more research is needed (Latronico et al 2016).

The optimal time to stop treatment is still being discussed. Considerations include the child’s actual and potential height, synchronisation of puberty with siblings and peers, psychological development and level of personal distress (Carel et al 2009, Latronico et al 2016, Pereira 2023). Vargas Trujillo et al (2021) found that there was no ideal age – whether bone age or chronological age – for initiating or stopping treatment. In most cases, treatment is stopped when the child starts secondary school, ideally when their bone age is between 11.5 years and 12.5 years in girls and between 13.5 years and 14 years in boys (Lazar and Phillip 2012).

The alternative to treatment with GnRH agonists is not to treat and let puberty occur at an earlier age than normal. There is a lack of research into the implications of not treating CPP, but there is evidence that not treating it can affect children’s final height and result in significant emotional and psychological distress (Gaudino et al 2020). Treatment of children aged under seven years is regarded as uncontroversial (Berberoğlu 2009).

In the US, another form of treatment, the histrelin acetate subcutaneous implant, has been introduced (histrelin is a GnRH agonist) (Popovic et al 2022). A minor surgical procedure is required but there is no need for injections and one implant lasts for 12 months. Some Asian countries have also started to consider the use of alternative treatments based on medicinal plants (Han et al 2022).

Decision-making about treatment

The decision to treat or not to treat CPP needs to be made in a process of shared decision-making between children, parents and specialists such as endocrine nurses and paediatric endocrinologists (Légaré et al 2011). Children and parents need to be empowered to engage in discussions about treatment (Royal College of Nursing 2019) and nurses should encourage them to take an active part in the decision-making process. Families need clear and comprehensive information on the available options and on the expected benefits and risks of treatment, as well as information on treatment timeframes and administration methods (Özakar Akça et al 2020). For nurses, it is important to allow sufficient time for these discussions with families and to use age-appropriate language.

There are many aspects to consider, including the cost of treatment, and decisions must be taken based on the individual needs of the child and their family. Individual factors to consider include height, treatment burden, psychosocial and emotional distress, and schooling and puberty stage in peers.

Height

Growth in children with CPP starts earlier and occurs faster than normal, but also stops before children reach their potential final adult height. One of the arguments in favour of treatment is that it can enable children to reach their final adult height (Lin et al 2017, Swaiss et al 2017, Luo et al 2021). GnRH agonists have been shown to prevent the premature fusion of the growth plates, thereby preserving the growth potential (Głab et al 2016). Shim et al (2020) have shown that long-term treatment with GnRH agonists improves the growth potential in boys with CPP. However, according to Guaraldi et al (2016) and Korkmaz et al (2019), treatment only produces a significant difference in final adult height if it is started before the age of seven years.

In terms of height, boys experience a larger pubertal growth than girls (Guaraldi et al 2016), so gender is an important factor to consider, with girls potentially benefiting less from treatment in terms of final adult height. Furthermore, treatment may be more useful in children whose bone age suggests a short future stature – that is, lower than their target range based on their parents’ height.

Researchers in Asia have started to investigate the effects on final adult height of treatment with GnRH agonists combined with growth hormone. Kim et al (2019) found that this treatment combination provided additional height, but their data were collected retrospectively. Gu et al (2019) conducted a meta-analysis of studies using this treatment combination in girls with CCP, but the majority of studies were retrospective non-randomised trials. Zhu et al (2021) suggested that using growth hormone alongside GnRH agonists was not cost-effective, which may prompt research into how to increase the cost-effectiveness of combined treatments.

The evidence has been deemed too weak to make conclusions about the benefits and risks of treatment with GnRH agonists in terms of other long-term negative consequences of CPP, such as loss of fertility and malignant or metabolic diseases (Luo et al 2021).

Treatment burden

Treatment with GnRH agonists involves intramuscular injections every one, three or six months for as many years as required. This carries a risk of infection, abscesses and scarring, and children may find the injections stressful and painful, especially if they do not fully understand why they are receiving them (Pereira 2023). When children belong to a group in whom the benefits of treatment are more likely to be minimal, for example older girls with a very advanced bone age, undergoing long-term and potentially burdensome and painful treatment may not be in their best interests.

The monitoring of treatment is likely to involve blood tests and stimulation tests. In the hospital setting, play specialists are available to support children undergoing painful procedures (Whitaker 2023), but because of the workload in endocrinology services, injections are also administered in GP practices where play specialists are not available (British Society for Paediatric Endocrinology and Diabetes 2022). The prospect of numerous injections and blood tests may lead families to decide against treatment, particularly if their child has needle phobia. However, with the development of more child-friendly monitoring procedures, more families may opt for treatment.

Psychosocial and emotional distress

Another factor to consider is the distress caused by CPP in children and families (Pereira 2023). There is evidence that CPP can lead to psychological and emotional distress, which may justify treatment (Weichold et al 2003, Bangalore Krishna et al 2019). The emotional and psychological effects of precocious puberty can negatively affect children’s social life, including in school (Kim and Lee 2012). Johansson and Ritzén (2005) argued that the short and long-term psychosocial effects of precocious or early normal puberty are probably more significant for children and families than the moderate loss in final height. However, in the past, paediatric endocrinologists have focused more on final height than on psychosocial outcomes (Johansson and Ritzén 2005). Also, research into the use of GnRH agonists to alleviate the negative psychological effects of CPP on children has been scarce and produced contradictory results (Dorn 2007, Carel et al 2009).

Research in adults has shown that treatment with GnRH agonists helps with mood and cognition (Grigorova et al 2006, Wojniusz et al 2016, Schoelwer et al 2017) and Yu et al (2019b) found evidence that mood had improved in girls with CPP after one year of treatment with GnRH agonists.

Further evidence is needed to make definitive recommendations about treatment.

Puberty stage in peers and schooling

A further factor to consider would be whether to synchronise the timing of the child’s puberty to match that of any siblings who have progressed through puberty, as well as considering whether any of the child’s peers are also progressing through puberty and whether the child is in primary or secondary school (Pereia 2023). One study in Iran showed a significant difference in mental health and social adjustment between children who had started puberty in primary school or in secondary school (Eskandaripour and Sepehrianazar 2021). Most children go through puberty once they are in secondary school; therefore, children with CPP who have gone through treatment would have more chances of having peers undergoing ‘normal’ puberty in secondary school than in primary school. Furthermore, primary schools may not be as well-equipped as secondary schools to support children experiencing puberty.

Conclusion

CPP is associated with negative physical health consequences in the long term and can have negative psychosocial effects, particularly in adolescence. At present, the treatment of CPP is invasive and potentially burdensome and painful, so the benefits of treatment need to be carefully weighed against the risks when deciding whether or not to treat the condition. All aspects of the child’s physical and psychosocial health and well-being need to be considered in the decision-making process, as well as the individual needs of the child and family. Children and families must be encouraged to take part in any treatment decisions. Because children’s nurses have a broad understanding of CPP, they can support children and families by identifying potential signs and referring children as early as possible for specialist assessment.

References

  1. Alotaibi MF (2019) Physiology of puberty in boys and girls and pathological disorders affecting its onset. Journal of Adolescence. 71, 63-71. doi: 10.1016/j.adolescence.2018.12.007
  2. Bangalore Krishna K, Fuqua JS, Rogol AD et al (2019) Use of gonadotropin-releasing hormone analogs in children: update by an international consortium. Hormone Research in Paediatrics. 91, 6, 357-372. doi: 10.1159/000501336
  3. Berberoğlu M (2009) Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. Journal of Clinical Research in Pediatric Endocrinology. 1, 4, 164-174. doi: 10.4274/jcrpe.v1i4.3
  4. Binder G, Lehrian TJ, Hoffmann E et al (2021) Adolescent boys with constitutional delay of growth and puberty grow faster than patients with organic growth hormone deficiency. Clinical Endocrinology, 94, 2, 237-241. doi: 10.1111/cen.14358
  5. Brambilla I, Guarracino C, Pistone C et al (2023) Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty. Italian Journal of Pediatrics, 49, 1, 100. doi: 10.1186/s13052-023-01506-8
  6. British Society for Paediatric Endocrinology and Diabetes (2022) Shared Care Guidelines: Use of Gonadotrophin Releasing Hormone (GnRH) Agonists – Triptorelin. http://www.bsped.org.uk/media/1978/gnrh-agonists-shared-care-guidelines-final-version-march-2022.pdf (Last accessed: 10 November 2023.)
  7. Brito VN, Canton AP, Seraphim CE et al (2023) The congenital and acquired mechanisms implicated in the etiology of central precocious puberty. Endocrine Reviews, 44, 2,193-221. doi: 10.1210/endrev/bnac020
  8. Carel JC, Eugster EA, Rogol A et al (2009) Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 123, 4, e752-e762.
  9. Carel J, Léger J (2008) Clinical practice. Precocious puberty. New England Journal of Medicine. 358, 22, 2366-2377. doi: 10.1056/NEJMcp0800459
  10. Copeland W, Shanahan L, Miller S et al (2010) Outcomes of early pubertal timing in young women: a prospective population-based study. American Journal of Psychiatry. 167, 10, 1218-1225. doi: 10.1176/appi.ajp.2010.09081190
  11. Day FR, Elks CE, Murray A et al (2015) Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Scientific Reports. 5, 11208. doi: 10.1038/srep11208
  12. Desmangles JC, Lappe JM, Lipaczewski G et al (2006) Accuracy of pubertal Tanner staging self-reporting. Journal of Pediatric Endocrinology and Metabolism. 19, 3, 213-221. doi: 10.1515/jpem.2006.19.3.213
  13. Dorn LD (2007) Psychological and social problems in children with premature adrenarche and precocious puberty. In Pescovitz OH, Walvoord EC (Eds) When Puberty Is Precocious: Scientific and Clinical Aspects. Humana Press, Totowa NJ, 309-327.
  14. Donaldson MD, Gregory JW, Van-Vliet G et al (2019) Puberty. In Practical Endocrinology and Diabetes in Children. 4. John Wiley & Sons, Chichester, 115-142.
  15. Eskandaripour M, Sepehrianazar F (2021) Comparison of social adjustment, school satisfaction, and mental health in girls with and without precocious puberty. Patient Safety and Quality Improvement Journal. 9, 4, 217-223. doi: 10.22038/psj.2021.54881.1305
  16. Eugster EA (2019) Treatment of central precocious puberty. Journal of the Endocrine Society. 3, 5, 965-972. doi: 10.1210/js.2019-00036
  17. Fuqua JS (2013) Treatment and outcomes of precocious puberty: an update. Journal of Clinical Endocrinology & Metabolism. 98, 6, 2198-2207. doi: 10.1210/jc.2013-1024
  18. Gaudino R, Calcaterra V, Farello G et al (2020) Diagnosis of precocious puberty in girls. International Journal of Pediatrics and Child Health. 8, 1-8. doi: 10.12974/2311-8687.2020.08.1
  19. Głab E, Wikiera B, Bieniasz J et al (2016) The influence of GnRH analog therapy on growth in central precocious puberty. Advances in Clinical and Experimental Medicine. 25, 1, 27-32. doi: 10.17219/acem/31433
  20. Grigorova M, Sherwin BB, Tulandi T (2006) Effects of treatment with leuprolide acetate depot on working memory and executive functions in young premenopausal women. Psychoneuroendocrinology. 31, 8, 935-947. doi: 10.1016/j.psyneuen.2006.05.004
  21. Gu Q, Luo Y, Ye J et al (2019) Comparative efficacy and safety of three current clinical treatments for girls with central precocious puberty: a network meta-analysis. Endocrine Practice. 25, 7, 717-728. doi: 10.4158/EP-2019-0008
  22. Guaraldi F, Beccuti G, Gori D et al (2016) Management of endocrine disease: long-term outcomes of the treatment of central precocious puberty. European Journal of Endocrinology. 174, 3, R79-R87. doi: 10.1530/EJE-15-0590
  23. Guimiot F, Chevrier L, Dreux S et al (2012) Negative fetal FSH/LH regulation in late pregnancy is associated with declined kisspeptin/KISS1R expression in the tuberal hypothalamus. Journal of Clinical Endocrinology and Metabolism. 97, 12, E2221-E2229. doi: 10.1210/jc.2012-2078
  24. Han XX, Zhao FY, Gu KR et al (2022) Development of precocious puberty in children: surmised medicinal plant treatment. Biomedicine and Pharmacotherapy. 157, 113907. doi: 10.1016/j.biopha.2022.113907
  25. Homaei A, Golmohammadi R, Saffari F (2021) Causes of precocious puberty in children referred to an endocrine clinic in Qazvin City, Iran from 2006 to 2018. Journal of Pediatrics Review. 9, 4, 337-346. doi: 10.32598/jpr.9.4.960.1
  26. Jee YH, Jumani S, Mericq V (2023) The association of accelerated early growth, timing of puberty, and metabolic consequences in children. Journal of Clinical Endocrinology & Metabolism. 108, 9, e663-e670. doi: 10.1210/clinem/dgad202
  27. Johansson T, Ritzén EM (2005) Very long-term follow-up of girls with early and late menarche. Endocrine Development. 8, 126-136. doi: 10.1159/000084098
  28. Kaplowitz PB (2021) For premature thelarche and premature adrenarche, the case for waiting before testing. Hormone Research in Paediatrics, 93, 9-10, 573-576. doi: 10.1159/000512764
  29. Kim EY, Lee MI (2012) Psychosocial aspects in girls with idiopathic precocious puberty. Psychiatry Investigations, 9, 1, 25-28. doi: 10.4306/pi.2012.9.1.25
  30. Kim M, Koh H, Lee G et al (2019) 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. Annals of Pediatric Endocrinology and Metabolism. 24, 2, 116-123. doi: 10.6065/apem.2019.24.2.116
  31. Korkmaz O, Sari G, Mecidov I et al (2019) The gonadotropin-releasing hormone analogue therapy may not impact final height in precocious puberty of girls with onset of puberty aged 6-8 years. Journal of Clinical Medicine Research. 11, 2, 133-136. doi: 10.14740/jocmr3710
  32. Kvernebo Sunnergren K, Dahlgren J, Ankarberg-Lindgren C (2023) Mini review shows that a testicular volume of 3 mL was the most reliable clinical sign of pubertal onset in males. Acta Paediatrica. 112, 11, 2300-2306. doi: 10.1111/apa.16899
  33. Lahlou N, Carel JC, Chaussain JL et al (2000) Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. Journal of Pediatric Endocrinology and Metabolism. 13, Suppl1, 723-737. doi: 10.1515/jpem.2000.13.s1.723
  34. Latronico AC, Brito VN, Carel JC (2016) Causes, diagnosis, and treatment of central precocious puberty. The Lancet Diabetes and Endocrinology. 4, 3, 265-274. doi: 10.1016/S2213-8587(15)00380-0
  35. Lazar L, Phillip M (2012) Pubertal disorders and bone maturation. Endocrinology and Metabolism Clinics of North America. 41, 4, 805-825. doi: 10.1016/j.ecl.2012.08.003
  36. Légaré F, Stacey D, Pouliot S et al (2011) Interprofessionalism and shared decision-making in primary care: a stepwise approach towards a new model. Journal of Interprofessional Care. 25, 1, 18-25. doi: 10.3109/13561820.2010.490502
  37. Lin YC, Lin CY, Chee SY et al (2017) Improved final predicted height with the injection of leuprolide in children with earlier puberty: a retrospective cohort study. PLoS One. 12, 10, e0185080. doi: 10.1371/journal.pone.0185080
  38. Luo X, Liang Y, Hou L et al (2021) Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: a systematic review and meta-analysis. Clinical Endocrinology. 94, 5, 786-796. doi: 10.1111/cen.14410
  39. Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Archives of Diseases in Childhood. 44, 235, 291-303. doi: 10.1136/adc.44.235.291
  40. Muir A (2006) Precocious puberty. Pediatrics in Review. 27,10, 373-381. doi: 10.1542/pir.27-10-373
  41. Mushtaq T, Howard S (2023) Precocious puberty. http://bestpractice.bmj.com/topics/en-gb/1127 (Last accessed: 10 November 2023.)
  42. Orlowski M, Sarao MS (2023) Physiology, Follicle Stimulating Hormone. StatPearls Publishing, Treasure Island FL.
  43. Özakar Akça S, Turan AP, Peltek Kendirci HN (2020) Precocious puberty and role of pediatric nurse. Zeynep Kamil Tıp Bülteni. 51, 1, 53-58. doi: 10.16948/zktipb.423576
  44. Pereira N (2023) Precocious puberty. In Chung PH, Rosenwaks Z (Eds) Problem-Focused Reproductive Endocrinology and Infertility. Springer, Cham, 11-18.
  45. Pinhas-Hamiel O, Czernichow P, Zeitler P et al (2014) Normal growth and growth disorders. In Kappy MS, Allen DB, Geffner ME (Eds) Pediatric Practice – Endocrinology. 2. McGraw-Hill Medical, London, 23-76.
  46. Popovic J, Geffner ME, Rogol AD et al (2022) Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States. Frontiers in Pediatrics. 10, 968485. doi: 10.3389/fped.2022.968485
  47. Roberts C (2016) Tanner’s puberty scale: exploring the historical entanglements of children, scientific photography and sex. Sexualities. 19, 3, 328-346. doi: 10.1177/1363460715593477
  48. Royal College of Nursing (2019) An Integrated Career and Competency Framework for Children and Young People’s Endocrine Nurse Specialists. http://www.rcn.org.uk/professional-development/publications/pub-007-287 (Last accessed: 10 November 2023.)
  49. Schoelwer MJ, Donahue KL, Didrick P et al (2017) One-year follow-up of girls with precocious puberty and their mothers: do psychological assessments change over time with treatment? Hormone Research in Paediatrics. 88, 5, 347-353. doi: 10.1159/000479688
  50. Shim YS, Lim KI, Lee HS et al (2020) Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty. PLoS One. 15, 12, e0243212. doi: 10.1371/journal.pone.0243212
  51. Spaziani M, Tarantino C, Tahani N et al (2021) Hypothalamo-pituitary axis and puberty. Molecular and Cellular Endocrinology. 520, 111094. doi: 10.1016/j.mce.2020.111094
  52. Swaiss HH, Khawaja NM, Farahid OH et al (2017) Effect of gonadotropin-releasing hormone analogue on final adult height among Jordanian children with precocious puberty. Saudi Medical Journal. 38, 11, 1101-1107. doi: 10.15537/smj.2017.11.21187
  53. Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Archives of Disease in Childhood. 51, 3, 170-179. doi: 10.1136/adc.51.3.170
  54. Tonini G, Lazzerini M (2000) Side effects of GnRH analogue treatment in childhood. Journal of Pediatric Endocrinology and Metabolism. 13, Suppl1, 795-804. doi: 10.1515/jpem.2000.13.s1.795
  55. Vargas Trujillo M, Dragnic S, Aldridge P et al (2021) Importance of individualizing treatment decisions in girls with central precocious puberty when initiating treatment after age 7 years or continuing beyond a chronological age of 10 years or a bone age of 12 years. Journal of Pediatric Endocrinology and Metabolism. 34, 6, 733-739. doi: 10.1515/jpem-2021-0114
  56. Vurallı D, Gönç EN, Özön ZA et al (2020) Adequacy of basal luteinizing hormone levels in the diagnosis of central precocious puberty. Turkish Archives of Pediatrics. 55, 2, 131-138. doi: 10.14744/TurkPediatriArs.2019.03708
  57. Weichold K, Silbereisen RK, Schmitt-Rodermund E (2003) Short-term and long-term consequences of early versus late physical maturation in adolescents. In Hayward C (Ed) Gender Differences at Puberty. Cambridge University Press, Cambridge, 241-276.
  58. Whitaker JM (2023) Defining play in the healthcare setting: a UK perspective. In Perasso G, Ozturk Y (Eds) Handbook of Research on Play Specialism Strategies to Prevent Pediatric Hospitalization Trauma, IGI Global, Hershey PA, 1-21.
  59. Wojniusz S, Callens N, Sütterlin S et al (2016) Cognitive, emotional, and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty. Frontiers in Psychology. 7, 1053. doi: 10.3389/fpsyg.2016.01053
  60. Yu HK, Liu X, Chen JK et al (2019a) Pelvic ultrasound in diagnosing and evaluating the efficacy of gonadotropin-releasing hormone agonist therapy in girls with idiopathic central precocious puberty. Frontiers in Pharmacology. 10, 104. doi: 10.3389/fphar.2019.00104
  61. Yu R, Yang S, Hwang IT (2019b) Psychological effects of gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty. Journal of Paediatric Endocrinology and Metabolism. 32, 10, 1071-1075. doi: 10.1515/jpem-2019-0108
  62. Yüce Ö, Bideci A, Çelik N et al (2020) Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment. Archives of Endocrinology and Metabolism. 64, 2, 121-127. doi: 10.20945/2359-3997000000212
  63. Zacharin M, Banerjee I, Patel L (2013) Puberty: normal and abnormal. In Zacharin M (Ed) Practical Pediatric Endocrinology in a Limited Resource Setting. Elsevier, London, 27-67.
  64. Zhu J, Zhang Q, Fang Y et al (2021) PDG10 Cost-effectiveness analysis of GnRH analogue ALONE versus combined growth hormone for girls with central precocious puberty. Value in Health. 24, Suppl 1, S88-S89. doi: 10.1016/j.jval.2021.04.458

Share this page

Related articles

How play specialists can reduce use of anaesthesia during radiotherapy
Radiotherapy practice is complex and daunting for children....

Parents’ spiritual and religious needs in young oncology
Aim To identify the spiritual and religious needs of young...

Rehabilitation for adolescent brain tumour survivors
Adolescent patients who recover from treatment for brain...

Young people’s and carer’s views on the cancer services they receive
Patient and public involvement is key to understanding how...

Brain tumours in children: reducing time to diagnosis
Although the leading cause of childhood, cancer-related...