Increasing global incidence of central precocious puberty

Precocious puberty is a prevalent endocrine disorder that affects children globally. Classically, precocious puberty is defined as the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys and it has a clear female predominance. The premature activation of hypothalamic gonadotropin-releasing hormone secretion leads to central precocious puberty (CPP), the most common mechanism of abnormal premature sexual development. Epidemiological studies based on national registries have estimated the prevalence and incidence of CPP in children originating from different populations in the last 2 decades (1–4).

Table. Four longitudinal epidemiologic studies on the incidence and prevalence of precocious pubertal development based on national registries. PP: precocious pubertal development, CPP: central precocious puberty, PT: premature thelarche, PA: premature adrenarche. # 20-year mean annual incidence rate of CPP

A Danish study (1993–2001) involving 670 children with precocious pubertal development estimated that 0.2% of girls and <0.05% of boys had some form of precocious pubertal development (1). More recently, a new Danish study (1998–2017) involving a very large group of patients (8596 children) with CPP, premature thelarche and premature adrenarche was reported (2). The 20-year mean annual incidence rate of CPP was 9.2 per 10,000 girls and 0.9 per 10,000 boys. There was a sixfold increase in incidence for girls, from 2.6 per 10,000 to 14.6 per 10,000, and a 15-fold increase for boys, from 0.1 per 10,000 to 2.1 per 10,000. These findings strongly suggested that the annual incidence of CPP has substantially increased in Denmark during the last 20 years.

Similarly, two epidemiological longitudinal studies demonstrated a significant increase of CPP in children from Korea (3–4). The first study (2004–2010) estimated the prevalence of CPP at 55.9 per 100,000 girls and 1.7 per 100,000 boys. Notably, the annual incidence of CPP in girls also significantly increased from 3.3 to 50.4 per 100,000 girls in this initial study, especially in the older age group (>6 years of age). The second Korean study (2008–2014) involved a very large number of Korean children from both sexes (37,890 girls and 1220 boys). It showed an overall incidence of CPP of 193.2 per 100,000 children (girls 410.6 and boys 10.9).

Multiple factors can influence the timing and tempo of puberty, including genetics, lifestyle, nutrition and environmental exposures. The mechanisms underlying the increasing trend in incidence of CPP are uncertain. The growing influence of nutritional status (overweight or obesity) has been highlighted as a major influence on the premature pubertal development, especially in girls. Other potential mechanisms include prenatal and postnatal exposures to endocrine disruptors, international adoption, physical activity, use of electronic devices and psychological influence. Very recently, an increased incidence of precocious and accelerated puberty was demonstrated in a small cohort of Italian girls during and after lockdown for the coronavirus 2019 (5). This fact was potentially related to weight gain, frequent use of electronic devices and stress.Notably, earlier age at puberty has been associated with a higher risk of metabolic, oncologic (breast cancer in girls) and cardiovascular disorders during adulthood. Therefore, the evidence of increasing prevalence and incidence of CPP can amplify the occurrence of other diseases, resulting in adverse long-term health outcomes.

Internal Medicine Department, Division of Endocrinology & Metabolism, Sao Paulo Medical School, Sao Paulo University, Brazil
  • Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Pediatrics 2005; 116: 1323–13282.
  • Trends in the incidence of central precocious puberty and normal variant puberty among children in Denmark, 1998 to 2017. Bräuner EV, Busch AS, Eckert-Lind C, Koch T, Hickey M, Juul A. JAMA Netw Open 2020; 3: e20156653.
  • A significant increase in the incidence of central precocious puberty among Korean Girls from 2004 to 2010. Kim SH, Huh K, Won S, Lee KW, Park MJ. PLoS One 2015; 10: e01418444.
  • Incidence and prevalence of central precocious puberty in Korea: An Epidemiologic Study Based on a National Database. Kim YJ, Kwon A, Jung MK, Kim KE, Suh J, et al. J Pediatr 2019; 208: 221–2285.
  • Increased incidence of precocious and accelerated puberty in females during and after the Italian lockdown for the coronavirus 2019 (COVID-19) pandemic. Stagi S, Mais S, Bencini E, Losi S, Paci S, Parpagnoli M, Ricci F, Ciofi ,Azzari C. Ital J Pediatr 2020; 46: 165.
Martin Savage
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