Thelarche, Pubarche, and Menarche Attainment in Children With Normal and Elevated Body Mass Index

MATERIALS AND METHODS

Data were obtained from NHANES III.^17–19 NHANES III was a survey of the civilian noninstitutionalized US population conducted from 1988 to 1994 that included NHW subjects with intentional oversampling of NHB and Mexican-American (MA) subjects to increase statistical reliability in these minority groups. In 8- through 18-year-old children, pubertal signs were ascertained by inspection, whereas age of menarche was determined by questionnaire. Height and weight were measured, and BMI was computed. Centers for Disease Control and Prevention BMI percentile tables^20,21 were used to convert NHANES BMI values into age- and gender-specific BMI percentile levels.

Models were fit to estimate the prevalence of attainment of the key pubertal stage variables by age in the major ethnic groups, as well as in the general population.^22,23 Fieller's method was applied to the output of these models to estimate ages, with 95% confidence intervals (CIs), at which a given percentage of children had reached each landmark.²⁴ A Wald test based on the Taylor expansion of the difference (delta method) was used to test differences in estimated ages of attainment between subgroups.^25–27 Logit models were fit to compare attainment of these early pubertal milestones for children with excessive and normal BMI from ages 8 through 14 years, during which 98% of children reached these landmarks.²³ Children in this age range comprised 70% to 80% of the full sample. Logit models were adjusted for race and ethnicity; all of the models included the age-by-BMI-level interaction. Logit rather than probit models were used for this purpose because they yield more interpretable results in the form of odds ratios (ORs). The analysis excluded 59 children (32 boys and 27 girls) with severe physical or mental impairment that could influence body habitus or pubertal development. All of the analyses accounted for the survey sampling design through incorporation of sampling strata and clusters, as well as weights that adjusted for differential probability of selection. SEs were computed using the Taylor linearization method.²⁸ Statistical analyses were performed by using Stata 10.0 (Stata Corp, LP, College Station, TX).

RESULTS

Comparisons of Children With Excess Weight Versus Normal Weight

Models including adiposity showed that excess weight was associated with earlier breast development and pubarche in younger girls and with earlier menarche during the preteen years (Fig 1 and Table 1). Specifically, girls with excessive BMI were significantly more likely to exhibit stage 2 breast development at ages 8.0 (OR: 3.86) through 9.6 (OR: 2.02) years than their peers with normal BMI. Pubarche was also significantly more prevalent in girls with excessive weight from ages 8.0 (OR: 4.50) through 10.2 (OR: 1.87) years. In contrast, there was no evidence of an association between adiposity and pubarche in boys. Menarche was significantly more prevalent in heavier girls from ages 10.6 (OR: 3.93) through 12.9 (OR: 1.92) years. An estimated 5% of girls with excessive BMI attained menarche by age 10.2 years, which was 10 months earlier than when 5% of girls with normal BMI achieved this milestone, at age 11.0 years (Table 2). The median age differed by almost half this much (5.4 months), which remained statistically significant. These associations of early pubertal landmarks with adiposity were independent of race or ethnicity.

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FIGURE 1

Logit plots for the prevalence of pubertal milestones according to age and BMI status. Stage 2 breast development differed significantly according to BMI status from ages 8.0 through 9.6 years, with respective ORs of 3.86 (95% CI: 1.16–12.9) and 2.02 (95% CI: 1.00–4.08). Similarly, pubarche in girls differed significantly by BMI status from ages 8.0 (OR: 4.50 [CI: 1.52–13.3]) through 10.2 years (OR: 1.87 [CI: 1.02–3.43]). Menarche differed significantly by BMI status from ages 10.6 (OR: 3.93 [CI: 1.02–15.1]) through 12.9 years (OR: 1.92 [CI: 1.01–3.64]). There was no evidence of an association between excess adiposity and pubarche in boys. A, Breast stage 2; B, pubic hair stage 3, girls; C, menarche; D, pubic hair stage 3, boys.

DISCUSSION

This report provides normative estimates for the ages at which thelarche, pubarche, and menarche occur in US children with a normal BMI. These results indicate that, in the general population of children of normal weight, breast and sexual pubic hair development, both ascertained by inspection, are unusual before 8 years of age in girls, and pubarche is unusual before 10 years of age in boys, occurring in <2%. However, adiposity and ethnicity are independently associated with earlier pubertal development in girls. An elevated BMI was associated with significantly greater odds of breasts appearing among younger girls, although the extent to which this is real (true breast tissue) or artifactual (adipomastia) is unknown. Excessive weight was clearly associated with significantly greater odds of earlier pubarche and menarche.

It is noteworthy that our analysis showed that an elevated BMI (≥85th percentile) was associated with significantly greater odds of attainment of thelarche and pubarche up to age 10 years. The differences in prevalence were most pronounced among the earliest developers and waned as prevalence increased so that they were no longer significant by the median age of attainment. This suggests that a subset of the population is sensitive to the onset of puberty being accelerated by an increase in adiposity that is too small to affect the majority. This may explain why previous estimates from NHANES III that did not take BMI into account differ from ours at the most by 0.2 years (for the median age of breast budding for NHB girls).^3,4 The differences in prevalence of menarche between girls with elevated and normal BMI were similarly more pronounced at younger ages, with the odds of girls with elevated BMI experiencing menarche being significantly greater throughout the preteen years, when the majority of girls attained this landmark. Our analysis does not exclude the possibility of a dose-response effect of adiposity, such that frank obesity may advance the average age of attainment of all of these milestones; the NHANES III database does not have sufficient subjects with BMI >95th percentile for a robust test of this possibility. On the other hand, it is well known that a high BMI does not necessarily indicate increased adiposity,¹⁵ so that girls with high BMI who undergo puberty later may actually have a greater proportion of muscle tissue.

Our results add to the evidence that the ongoing epidemic of childhood obesity seems to be a major determinant of an earlier age of attainment of pubertal milestones in the United States over the past several decades. Our data are consistent with the evidence that overweight is approximately 1.5-fold more prevalent and obesity approximately twofold more prevalent in girls who mature at an earlier-than-average age⁷ and that an overweight girl is ≥2 times as likely to achieve menarche as an average-weight girl of the same age.¹³

Notably, ethnic differences existed independent of excess adiposity: NHB and MA girls with normal BMI achieved all of the pubertal landmarks earlier than NHW girls with normal BMI. Our analysis indicates that thelarche is normal in NHB and MA nonobese girls before 8 years of age, although pubarche is not. Although the 5th percentile for thelarche clearly occurs before 8.0 years of age in NHB and MA girls of normal weight, the lack of data on the normal population of 6- to 8-year-old girls in these ethnic groups precludes making a reliable estimate of when this milestone is achieved.

CONCLUSIONS

The practical implication of our analysis is that BMI should be a major consideration in the evaluation of pubertal development that occurs before 8 years of age. In part, this is because excess adiposity confounds the distinction between breast tissue and adipomastia. However, excess adiposity also advances the onset of puberty modestly in a subset of girls. Although the appearance of breasts before 8 years of age can be considered premature in NHW girls with normal BMI, occurring in <5% of them, it seems to be normal in 7-year-old NHB and MA girls with normal BMI. In contradistinction, sexual pubic hair development before 8 years (10 years in boys) is premature in children with normal BMI of all of these ethnic groups.