Estradiol (E2) from the ovary accounts for most of the circulating estrogens, although there is a small amount of extraovarian conversion from androstenedione (to estrone) and testosterone (to estradiol). In addition to stimulating breast growth and maturation of the vaginal mucosa, estrogen has profound effects on the skeleton, being the primary hormone responsible for epiphysial closure. At higher doses, estrogen causes epiphyseal fusion and, therefore, termination of linear growth. The mechanism by which this occurs is thought to involve estrogen’s stimulation of chondrogenesis on the epiphyseal growth plate.¹

Although the testes represent the primary source of this hormone, a small amount is generated from the extratesticular conversion of the adrenal hormone androstenedione in both males and females. Testosterone is the primary hormone responsible for the voice change in males and attainment of male body habitus, but it is dihydrotestosterone, the product of conversion of testosterone by 5α-reductase, that causes phallic and prostate growth.

The exact triggers for the pulsatile hypothalamic release of GnRH that occurs around the time of puberty are incompletely understood, although three distinct changes are observed.

Kisspeptins refer to a class of peptides encoded by the KISS1/Kiss1 gene that act through the receptor, GPR54. These compounds appear to stimulate LH through GnRH at the hypothalamic level and are implicated as necessary for pubertal onset, as well as normal reproductive function.³

This product of the ob gene produced by fat cells was initially thought to have a gateway role in pubertal development. It was discovered to play a key role in the regulation of appetite, food intake, and energy expenditure, providing a signal to the central nervous system regarding satiety and the amount of energy stored in adipose tissue.⁴ With further investigation, its role has been identified as more modest; it appears that leptin is permissive for pubertal advancement at the hypothalamic level by modulation of the GnRH system, although it has also been shown to have effects at other levels of the HPG axis.⁵

During puberty, the breasts develop and the ovaries, uterus, vagina, labia, and clitoris increase in size, with the uterus and ovaries increasing in size by approximately five-fold to seven-fold. Body composition changes, as girls accumulate fat mass at an average annual rate of 1.14 kg/year.⁸

Often, the earliest physical sign of puberty in girls is thelarche, although few girls have pubic hair development as the first sign. On average, breast development starts at the age of 10 years for White girls and at 8.9 years for Black girls, according to a frequently cited large cross-sectional study.⁹ The Breast Cancer and the Environment Research Program (BCERP) examined >1,200 girls longitudinally over 7 years in three urban areas and reported age at thelarche by both visual inspection as well as palpation (in contrast to the Pediatric Research in Office Settings (PROS) study which employed only inspection); median age of thelarche (SMR B2) was 8.8 for Black girls, 9.3 years for Hispanic, and 9.7 years for Caucasian and Asian participants. Notably, higher body mass index (BMI) was associated with earlier attainment of SMR 2.¹⁰ These physical findings, however, may be preceded by the growth spurt by approximately 1 year. As a result, the growth curve is an essential tool in the evaluation of precocious or delayed puberty. The average length of time for completion of puberty is 4 years, but can range from 1.5 to 8 years.

Menarche usually occurs during SMR B3 or B4, and approximately 3.3 years after the growth spurt, or roughly 2 years after breast budding. The normal range for menarche varies from 9 to 15 years and is dependent on such factors as race, socioeconomic status, heredity, nutrition, and culture. It occurs later at higher altitudes, in rural areas, and in larger families. Body composition also influences age at menarche, although controversy exists whether there is a necessary amount of adipose mass needed at the time of menarche.

Earlier menarche is usually correlated with shorter adult height, although this depends on the degree of estrogen stimulation before menses. Girls with higher or prolonged estrogen levels tend to grow less after menarche. On an average, girls grow 4 to 6 cm after menarche. The sequence of pubertal events in females is found in Figure 2.6. The age at menarche has gradually decreased during the last century. However, this trend has slowed significantly in the past few decades.

Several investigators have examined data from the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994.¹¹,¹²,¹³ One study¹² compared data from an earlier US survey 25 years previous to the NHANES III data and found that the average age at menarche had declined only minimally (i.e., by approximately 2.5 months, from 12.8 to 12.5 years). Another study cited up to a 4-month decrease in age at menarche.¹² Review of all available data in 2008 suggested a trend toward earlier menarche in the United States between 1940 and 1994, but with a magnitude of change of 2.5 to 4 months, revealing questionable clinical significance.¹⁴ All studies that have examined race have demonstrated that Black girls reach menarche the earliest, followed by Mexican American and White girls.

Although there are slight differences in the ages of onset, the trend is for earlier pubertal onset, but almost no change in the age at menarche. On an average, girls of Black descent appear to enter puberty earlier than their Hispanic and White counterparts. The large study from the PROS group sampled >17,000 White and Black girls from around the United States with the SMR method and found that the earliest signs of puberty are occurring earlier than previously described.⁸ In that study, the mean ages at onset of breast development were 8.9 years for Black girls and 10 years for White girls. Pubic hair development started at 8.8 years for Black girls and at 10.5 years for White girls. Similarly, Black girls experienced menarche at 12.2 years, and White girls at 12.9 years.