PUBERTY in girls occurs at an earlier age in the 21st century than it did 100 years ago, particularly in African American (AA) girls. By understanding the biological basis of puberty through laboratory studies and epidemiologic analyses, we may be able to begin to address this issue in the underserved population of AA adolescent girls.
THE NEUROBIOLOGY OF PUBERTY
Pubertal development in humans is manifested by changes in secondary sex characteristics in the body, including genital and breast development, the first appearance of axillary hair, and changes in body shape and composition. However, it is becoming increasingly clear that the pubertal process in mammals is stimulated by gonadotropin-releasing hormone (GnRH), produced in about 1,000 cells in the hypothalamus.1 GnRH is released from hypothalamic neurons in pulses of approximately hourly intervals, into a small capillary system that leads to the anterior pituitary. At the pituitary, GnRH regulates the release of 2 additional hormones released to control the synthesis and release of gonadal steroid hormones (estrogens, progestins, and androgens) and gametogenesis (sperm production in males, ovum production in females). While all 3 levels of this hypothalamic-pituitary-gonadal (HPG) axis must function for puberty to progress, the activation of neural GnRH cells is the primary driver.1
Prior to the activation of the HPG axis in infancy and childhood, GnRH secretion is minimal.2 At the onset of puberty in both males and females, pulsatile GnRH release increases significantly. Although it is not possible to measure GnRH release directly in humans, animal models have demonstrated how GnRH pulses change during puberty. Studies with rhesus monkey models show that prior to puberty, GnRH pulses are extremely small, occur at very low frequency, and increase in frequency and amplitude during subsequent pubertal development.3 These changes drive pubertal changes in pituitary and gonadal hormones.
SEX DIFFERENCES IN THE TIMING OF PUBERTY
Significant sex differences have been documented in the timing of puberty in humans. Puberty in American girls is associated with breast development, which occurs at an average age of 10.5 years, and menarche (first menses), occurring at 12.8 years when averaged for all races.2 Puberty in boys, which occurs slightly later, is associated with increased testicular size.2 Such sex difference also exists in rodent models.4 In our laboratory, we find that the timing of puberty differs in males and females, with the achievement of adult reproductive function occurring later in male rodents, as in humans.1
Disorders and effects of disruptions of puberty are also sexually dimorphic. Delayed puberty (the lack of development considered normal for pubertal age) is more prevalent in males than in females; precocious or early puberty5 is more common in females. The demographics of puberty have also shifted over the past century. The timing of puberty in girls has undergone a dramatic advance, while it has not changed very much for boys during this time.6 Hygienic and environmental improvements are thought to contribute, though it does not explain why male puberty seems unaffected.6 Nutritional standards have also improved, with increased obesity among children, which may also contribute to earlier puberty in girls, as fatty tissues accumulate estrogens, which are important for sex development.6,7 Boys who are overweight show delayed development when compared to boys of average weight.8 Other environmental factors also need to be considered to elucidate this sex difference in the timing of puberty.
Rodent models provide insights into mechanisms for the sex differences for puberty. Treatment of prepubertal rats with a drug to block the effects of GnRH on its pituitary gland target cells caused delayed puberty in male but not female rats.9 Surprisingly, effects of this drug on male reproduction were observed weeks after treatment had ceased. The effect was reversible but took up to a month for males to regain reproductive capacity. Rodent results are consistent with human findings for a higher prevalence of delayed puberty in males, and experimental studies from our laboratory and others allow us to better understand these processes in humans.
ETHNIC DIFFERENCES IN PUBERTY
The overall trend for earlier puberty in the last century is especially prevalent in AA girls, with Mexican Americans having puberty at an intermediate age.10 On average, AA girls go through puberty 1-1.5 years earlier than White girls (~age 9 years for AAs, ~10-10.5 years for Whites for breast development and the first appearance of pubic hair).10 Menarche, the first menstrual period, occurred at age 12.16 in AA and 12.88 in White girls.10 The reason for these racial differences is not well understood, but ethnic differences in food consumption and usage of products that contain estrogens are both possible factors. Several studies have noted that AA girls are larger in size prepubertally, which is thought to contribute to earlier development.11 The standards for precocious puberty have had to change to reflect these demographic trends. In females, puberty is now said to be precocious if it occurs before the age of 7 in White girls and the age of 6 in AA girls.5 Although precocious puberty may be considered benign, it may result in psychological or social problems and earlier sexual activity.5 Regardless of species, sex, or race, the precipitating factor for puberty is a change in the brain's release of the GnRH. This is a consideration for interventions for extremely early or late puberty, as pharmaceutical agents that stimulate or delay inappropriately late or early puberty are already in use.