Puberty: when is it normal?

C lassically, 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 the1 Endocrinology Unit Development, Laboratory of Hormones and Molecular Genetics, LIM-42, Division of Endocrinology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP, Brazil