Puberty is a complex process during which children attain secondary sexual characteristics and reproductive capability. Normal puberty is initiated by reactivation of the hypothalamic secretion of gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH), in turn, FSH and LH stimulates the gonadal development and sex steroid production. The first sign of pubertal onset is an increase in testicular volume above 4 mL (Tanner G2 stage) in boys and the first appearance of breast buds (Tanner B2 stage) in girls [1]. A number of factors including ethnicity, inheritance, stress, body fat and nutrition are known to be involved in the timing and tempo of pubertal development.

During the past decades, advancement in the age of pubertal development in girls has been reported all around the world. The age at thelarche has advanced about one year since mid-1980s and early 1990s among US white girls [2,3] and Danish girls [4]. With regards to menarche, trend toward earlier menarche is continuing in China [5] and Korea [6] since 1980s, meanwhile decrease in menarcheal age appears to be slowed down in developed nations such as US [7] Japan [8] and some European countries [9,10]. Also in boys, secular trend of earlier pubertal onset has been noted in US [11], Danmark [12], Korea [13], and China [14]. Interestingly, these secular trends of puberty have coincided with the worldwide increase in childhood obesity prevalence. A rapid increase of obesity prevalence in children has been noted in many countries including US [15], UK [16], Germany [17], France [17], Austrailia [18], Brazil [19], China [19], and Japan [20]. In Korea, the prevalence of childhood obesity increased from 5.8% in 1997 to 9.7% in 2005 [21], and now it has reached 10-20% and among high schoolers [22]. Several epidemiologic studies have demonstrated that girls with greater body mass index (BMI) enter thelarche [5,23,24] or menarche [25] earlier than girls with normal BMI, leading to a suggestion that excess adiposity influence the onset and progression of puberty.

In this paper, we reviewed the possible mechanism by which obesity may influence pubertal maturation in children and summarized human studies showing impact of childhood obesity on the pubertal timing.

A number of evidences have demonstrated an associations between adiposity and early puberty in girls (Table 1). In 1997, Pediatric Research in Office Settings (PROS) study demonstrated that girls aged 6-9 years with breast development had higher BMI z-scores compared with prepubertal girls at each age [23]. Similarly, a study on pubertal development in black girls aged 8-10 years reported that increasing stages of breast development were related to increased BMI, waist circumference and fat mass [54]. A nationally representative study based on the data from the National Health Examination Survey (NHES 1963-1970) and National Health And Nutrition Examination Survey III (NHANES 1988-1944) was examined the trend of menarcheal age during the 25 year period [55]. The authors reported that menarcheal age advanced from 12.7 to 12.5 years and prevalence of overweight increased from 16% to 27% during the study period. And they also demonstrated that the average menarcheal age in 1988-1994 could be predictable based on the secular changes in distributions of BMI z-score, race, and age, suggesting causality exists between increasing obesity and advanced menarcheal age [55]. Other studies using NHANES III data demonstrated that prevalence of obesity and overweight is significantly higher in girls with early puberty than in control [24], vise versa, early puberty and early menarche are more prevalent in overweight girls than in normal weight girls [56]. Besides cross-sectional studies, there are some longitudinal studies that investigated the association of body composition and pubertal timing in girls. The Bolgalusa Heart study, which examined the relations between menarche and prepubertal adiposity, found that increased BMI z-score measured at aged of 5-9.9 years correlates earlier age (<11.0 years) at menarche [25]. A cohort study in Australia reported that overweight at age 5 years is a predictor for more advanced pubertal stages at age 14 years [57]. In a prospective study in Germany, higher prepubertal BMI was associated with earlier pubertal progression and shorter puberty duration, resulting earlier attainment of menarche [58]. Likewise, a recent prospective study demonstrated that fat mass at age 8 years was associated with advanced pubertal stage at age 11 years and BMI at age 11 years had negative association with the age of menarche [59]. As discussed earlier, small size at birth and childhood catch-up growth have been associated with increased risk of premature pubarche and early menarche, resulting from insulin resistance [48,49]. Although a large number of studies evaluated the association between adiposity and pubertal stage on physical examination, the relationship between adiposity and precocious puberty diagnosed with hormonal assay has been rarely discussed. Recently, we demonstrated that girls with precocious puberty has higher adiposity than control, and adiposity and central obesity is severer in girls with gonadotropin-independent precocious puberty puberty than in girls with gonadotropin-dependent precocious puberty [60]. This supports that obesity is a contributing factor for early puberty especially in girls with gonadotropin-independent precocious puberty.

There are fewer studies on a relationship between obesity and pubertal maturation in boys (Table 2). Contrary to the study results reporting significant associations between obesity and earlier puberty in girls, the relationship is mixed in boys according to the population studied. In a cross-sectional study in Italy, the obese boys tended to have delayed pubertal maturation [61]. Similarly, a large scaled US study based on NHANES III data, pubertal development was delayed in obese boys [24]. A more recent prospective study in US showed that boys in the highest BMI trajectory had a higher risk of later pubertal onset [62]. Putative mechanism of delayed puberty in obese boys was explained as increased circulating estrogens by increased aromatase activity in fat tissue. Increased estrogens, in turn, may inhibit gonadotropin secretion in negative feedback mechanism [63]. However, some longitudinal studies have demonstrated a positive relationships between pubertal onset and obesity in boys. A Spanish study [64] and an Australian study [57] reported a nagative relation between the age of pubertal onset and prepubertal BMI in boys. A Swedish population-based study [65] also demonstrated similar impact of childhood BMI on early pubertal onset and reduced height gain during puberty. A UK cohort study [48] showed low birth weight and catch-up growth increased the risk of premature pubarche in boys, as well in girls. Finally, the Copenhagen Puberty Study [12] evaluated the causal effect of increased adiposity on secular trends in earlier pubertal onset among Danish boys. The age at pubertal onset has decreased, whereas BMI z-score has increased between 1991-1993 and 2006-2008. Interestingly, after adjustment for BMI, the difference in the age of pubertal onset was no longer significant, suggesting the advancement of puberty was associated with increased BMI. So far, there is still inconsistency between the studies on impact of obesity on pubertal maturation in boys, although evidence that obesity might play a role in earlier onset of puberty is increasing.

A lot of large scaled epidemiologic studies indicate that secular trends of earlier pubertal maturation in girls are related with increased BMI or adiposity in the past 30 years. Activating effect of leptin on GnRH-gonadotropin axis is thought to be one of the possible mechanisms linking between body fat mass and earlier pubertal onset. Hyperinsulinemia in obesity may also contribute to earlier puberty by stimulation of androgen secretion, activation of aromatase in fat tissue and reduction of SHBG production from liver. Low birth weight and rapid catch up growth is known to be linked to hyperandrogenemia and subsequent early puberty. In contrast with girls, the data on the association of adiposity with pubertal onset in boys are much limited and, if any, the results are inconsistence. There are some limitations for studies in boys. Distinct pubertal milestones that can be easily obtained from an interview are not available, and pubertal staging by physical examination is more difficult in boys. Therefore, efforts are needed to overcome several limitations in future studies, such as objective pubertal staging, reliable measurement of body fat mass other than BMI, hormonal markers for pubertal development, and longitudinal study design to overcome genetic, nutritional and environmental variables.