Puberty: When is it normal?

Classically, the normal chronological age for pubertal onset is between 8 and 13 years in girls and 9 and 14 years in boys based on data from epidemiological studies from the 60’s (¹). However, the age limit for pubertal timing is still a challenge (²,³). It is well known that puberty is a complex and multi factorial process that involves genetic, metabolic, socio economic, nutritional and ethnic factors. Moreover, the evidence that initial pubertal signs, mainly in girls, are appearing earlier today than in the last 4 decades has been described by several epidemiological studies (²-⁴).

In the last years, genetic control of pubertal onset has been demonstrated through the identification of pathogenic mutations. Several loss-of-function mutations of MKRN3, a gene encoding the makorin RING-finger protein 3, result in familial central precocious puberty, suggesting a potential inhibitory input to gonadotropin-releasing hormone (GnRH) secretion (⁵). Interestingly, the mean age of pubertal onset in MKRN3 affected girls was 6.0 years (ranging from 3.0 yr to 7.0). Notably, pubertal timing, pubertal height growth and age at menarche are strongly associated with adiposity in both epidemiological and genetic studies, since genome-wide association studies revealed genetic loci linking pubertal height growth, pubertal timing and childhood adiposity (⁶). The relationship between pubertal timing and adiposity is stronger in girls. Environmental factors, such as endocrine chemical disruptors (pesticides, phthalates, bisphenol A, and plant-derived phytoestrogens) or low levels of estrogens in the food supply have been influenced the timing of puberty, leading to precocity or delay in this process, specially, in animal models (³).

It is reasonable to suppose that each population has peculiar epidemiological features that influence the age of pubertal onset. To establish the age of initial pubertal signs in the Brazilian population is a big task, not only due to the continental size of the country, but mainly due the population heterogeneity. The data of pubertal onset and its progression in Brazilian population is very scarce. Feibelmann and cols. (⁷) performed a relevant cross sectional epidemiological survey of age of breast development in girls in a representative population of 665 schoolgirls (aged 5.9 to 18 yr) in Uberaba, Minas Gerais, Brazil. The authors identified that mean chronological age of thelarche was 9.8 ± 1.4 yr (ranging from 7 to 12 yr) and pubarche 10.2 ± 1.4 yr (ranging from 7 to 13 yr). In addition, the mean age of menarche was 11.7 ± 1.3 yr (ranging from 9 to 14 yr). The interval between thelarche and menarche was 1.7 ± 1.3 years. Interestingly, black girls had thelarche and pubarche significantly earlier than white girls, reinforcing the influence of ethnicity.

It is well known that the decline reported for the mean age of thelarche is not accompanied of significant changes in the mean age of menarche (³,⁴). While in American and European studies, the reported mean age of menarche was 12.5 yr and mean interval between thelarche and menarche of 2.3 yr, in the Brazilian study both indicators were lower (11.7 yr for menarche and 1.7 yr for mean interval between thelarche and menarche) (³,⁷). In addition, the diagnosis of abnormal puberty (non progressive and progressive forms) was established in 4.7% of girls in the Feibelmann’ study (⁷). These findings reinforce the idea that the prevalence of sexual precocity is underestimated. In fact, parent’s education regarding the detection of first pubertal signs is essential for prompt recognition of precocious puberty (⁸,⁹).

Castilho and cols. (¹⁰) evaluated the secular trend of menarche according to body mass index (BMI). It was demonstrated that menarche in Brazilian girls has anticipated 3.24 months in the last 10 years, together with an increase of obesity prevalence. In the study by Feibelmann TC and cols. (⁷), the prevalence of overweight and obesity was 18.8 and 12.5%, respectively. Other studies have documented that higher BMI is correlated with earlier onset of puberty, implicating leptin, a fat cell-derived protein, and other adipokines required for normal gonadotropin secretion (³,⁶,⁹). However, it is not clear if increased adiposity is the cause or the consequence of early pubertal development in girls. Finally, other larger, longitudinal and multicenter epidemiological studies involving the Brazilian population will be necessary for understanding the complexity of normal and abnormal pubertal timing.

REFERENCES

• ¹
  Marshall WA, Tanner JM. Variations in pattern of puberal changes in girls. Arch Dis Child. 1969;44:291-303.
• ²
  Macedo DB, Cukier P, Mendonca BB, Latronico AC, Brito VN. Advances in the etiology, diagnosis and treatment of central precocious puberty. Arq Bras Endocrinol Metabol. 2014;58(2):108-17.
• ³
  Kaplowitz P. Update on precocious puberty: girls are showing signs of puberty earlier, but most do not require treatment. Adv Pediatr. 2011;58(1):243-58.
• ⁴
  Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research Office Settings Network. Pediatrics. 1997;99:505-12.
• ⁵
  Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013;368(26):2467-75.
• ⁶
  Cousminer DL, Berry DJ, Timpson NJ, Ang W, Thiering E, Byrne EM, et al. Early Growth Genetics (EGG) Consortium. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Hum Mol Genet. 2013;22(13):2735-47.
• ⁷
  Feibelmann TC, Silva AP, Resende DC, Resende EA, Scatena LM, Borges MF. Puberty in a sample of Brazilian schoolgirls: timing and anthropometric characteristics. Arch Endocrinol Metab. 2015;59(2):105-11.
• ⁸
  Midyett LK, Moore WV, Jacobson JD. Are pubertal changes in girls before age 8 benign? Pediatrics. 2003;111(1):47-51.
• ⁹
  Sorensen K, Mouritsen A, Aksglaede L, Hagen CP, Mogensen SS, Juul A. Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty. Horm Res Paediatr. 2012;77:137-45.
• ¹⁰
  Castilho SD, Pinheiro CD, Bento CA, Barros-Filho Ade A, Cocetti M. Secular trends in age at menarche in relation to body mass index. Arq Bras Endocrinol Metabol. 2012;56(3):195-200.

Publication Dates

• Publication in this collection
  Apr 2015

History

• Received
  31 Mar 2015
• Accepted
  31 Mar 2015