Precocious Puberty 

Precocious puberty refers to the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. For many years, puberty was considered precocious in girls younger than 8 years; however, recent studies indicate that signs of early puberty (breasts and pubic hair) are often present in girls (particularly black girls) aged 6-8 years. For boys, onset of puberty before age 9 years is considered precocious.

Early onset of puberty can cause several problems. The early growth spurt initially can cause tall stature, but rapid bone maturation can cause linear growth to cease too early and can result in short adult stature. The early appearance of breasts or menses in girls and increased libido in boys can cause emotional distress for some children.

Premature pubarche and premature thelarche are 2 common, benign, normal variant conditions that can resemble precocious puberty but are nonprogressive or very slowly progressive. Premature thelarche refers to the isolated appearance of breast development, usually in girls younger than 3 years; premature pubarche refers to appearance of pubic hair without other signs of puberty in girls or boys younger than 7-8 years. A thorough history, physical examination, and growth curve review can help distinguish these normal variants from true sexual precocity.

If the history, physical examination, and laboratory data suggest that a child exhibits early and sustained evidence of pubertal maturation, the clinician must differentiate central precocious puberty (CPP) from precocious pseudopuberty. Central precocious puberty, which is gonadotropin-dependent, is the early maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis, with the full spectrum of physical and hormonal changes of puberty. Precocious pseudopuberty is much less common and refers to conditions in which increased production of sex steroids is gonadotropin-independent (see Precocious Pseudopuberty). Correct diagnosis of the etiology of sexual precocity is critical, because evaluation and treatment of patients with precocious pseudopuberty is quite different than that for patients with central precocious puberty.

Most patients, particularly girls suspected of having central precocious puberty, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve. CNS imaging studies of these otherwise healthy 6-year-old to 8-year-old girls usually reveal no structural abnormalities. A study of 200 girls in France found abnormal brain imaging findings in 2% of girls whose onset of puberty was between age 6-8 years and in 20% of girls whose onset of puberty was before age 6 years.^[1] A smaller study from the United Kingdom reported abnormal findings in 15% of 67 girls.^[2] Abnormal CT scan or MRI findings are more frequent among boys with central precocious puberty than among girls with central precocious puberty.

The onset of puberty is caused by the secretion of high-amplitude pulses of gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesized mechanisms that suppress onset of puberty include (1) the HPG axis, which is highly sensitive to feedback inhibition by small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses.

CNS abnormalities associated with precocious puberty include the following:

• Tumors (eg, astrocytomas, gliomas, germ cell tumors secreting human chorionic gonadotropin [HCG])
• Hypothalamic hamartomas
• Acquired CNS injury caused by inflammation, surgery, trauma, radiation therapy, or abscess
• Congenital anomalies (eg, hydrocephalus, arachnoid cysts, suprasellar cysts)

High-amplitude pulses of GnRH cause pulsatile increases in the pituitary gonadotropin-luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Increased LH levels stimulate production of sex steroids by testicular Leydig cells or ovarian granulosa cells. Pubertal levels of androgens or estrogens cause the physical changes of puberty, including penile enlargement and sexual hair in boys and breast development in girls. These levels also mediate the pubertal growth spurt. Increased FSH levels cause enlargement of the gonads in both sexes and eventually promote follicular maturation in girls and spermatogenesis in boys.

Frequency

United States

The frequency of precocious puberty in girls and boys largely depends on the age at which the condition is considered precocious.

In 1969, Marshall and Tanner published the results of their study of 192 white British girls.^[3] These researchers stated that the average age of thelarche was 11 years and defined precocious puberty in girls as that which started before age 8 years. No studies that looked at the age of appearance of breast and pubic hair in normal children were performed in the United States during that same time. However, many in the United States had the impression that girls had been maturing earlier than in the past.

No data were available to confirm this impression until 1997, when Herman-Giddens et al reported on the incidence of breast and pubic hair development by age and race in 17,000 US girls aged 3-12 years.^[4] They used the established definition that breast or pubic development in girls was precocious before age 8 years and estimated that approximately 8% of white and 25% of black girls in the United States exhibited evidence of sexual precocity. The results of this study are illustrated in the images below.

In 1999, Kaplowitz and Oberfield published new guidelines recommending that puberty be considered precocious only when breast development or pubic hair appear before age 7 years in white girls and age 6 years in black girls.^[5] Based on these revised definitions and the 1997 data, an estimated 4-5% of girls from both racial groups are considered precocious in their pubertal maturation. Any child younger than age 8-9 years who demonstrates rapid pubertal progression or any girl who menstruates before age 9 years should be evaluated by a pediatric endocrinologist.

Reliable estimates of the frequency of precocious puberty in boys have not been published. However, several centers have reported that they evaluate between one fifth and one tenth as many boys as girls for sexual precocity. Whether early puberty in boys is becoming more common over time, as is the case in girls, is unclear. However, a study from Denmark found that the mean age of testicular enlargement in boys declined from age 11.92 years to 11.66 years between 1991-1993 and 2006-2008, suggesting that more boys may be starting puberty before age 9 years.^[6]

International

A review of trends in timing of puberty around the world showed no clear trend toward earlier puberty in northern Europe, but earlier mean age of menarche has been reported in some southern European countries and other warmer parts of the world.^[7] A report from Denmark showed that over a 15-year period (1991-1993 vs 2000-2008), the mean age at which breast tissue appeared in girls decreased from age 10.88 years to 9.86 years, with a much smaller decline in the mean age at menarche (age 13.42 y vs age 13.13 y).^[8] A study of over 20,000 girls from urban China done from 2003-2005 show that the mean age of breast development was 9.2 years, with the mean age at menarche falling to 12.27 years; about 20% of 8-year-old girls already had evidence of breast development.^[9] Thus, in certain parts of the world, a decline in the age of puberty in girls has been noted, with parallel changes seen in US girls.

An interesting and still unexplained finding is the high incidence of precocious puberty in girls adopted into Western Europe from various underdeveloped countries. This has been studied extensively in Denmark, where the mean age at thelarche and at menarche in international adopted girls was significantly lower than that observed in a reference group of Danish-born girls.^[10] Exposure to chemicals in the environment has been proposed as the cause, but the fact that LH, FSH, and estradiol levels rise earlier in adopted girls suggest that their earlier puberty is centrally mediated and not chemically induced.

Mortality/Morbidity

Isolated sexual precocity of unknown etiology carries no increased risk of mortality; however, distinguishing between children with idiopathic central precocious puberty and the rare patient with a CNS, adrenal, or ovarian tumor is important because the latter group may be at risk for tumor-related complications. Some, but not all, studies have found an association between early puberty in girls and a higher risk of breast cancer.

Children with precocious puberty may be stressed because of physical and hormonal changes they are too young to understand. They may be teased by their peers because of their physical difference. Girls who reach menarche before age 9-10 may become withdrawn and may have difficulty adjusting to wearing and changing pads. Both sexes, but more so boys than girls, may have increases in libido leading to increased masturbation or inappropriate sexual behaviors at a young age. Girls with a history of early puberty have a slightly earlier age of initiation of sexual activity.

Some studies have found that children with precocious puberty more frequently exhibit behavioral problems and are less socially competent than age-matched peers. Some, but not all, studies find evidence of emotional problems persisting into adulthood. The distress associated with early menses can be decreased if parents are encouraged to prepare their daughters for this event when they reach stage III-IV of breast development.

Early puberty accelerates growth. These children may initially be considerably taller than their peers. Because bone maturation is also accelerated, growth may be completed at an unusually early age, resulting in short stature. Short stature is more likely if puberty starts very early (ie, before age 6 y) than if it begins moderately early (ie, ages 6-8 y). Several studies show that most untreated girls with idiopathic central precocious puberty reach an adult height within the reference range. Determination of bone age can be used to predict adult height and to select patients with high risk for short stature if left untreated.

Race

The study by Herman-Giddens et al and the data from the National Health and Nutrition Examination Survey (NHANES) III study conclusively showed that black girls in the United States have onset of breast development and pubic hair about one year earlier than white girls; thus, using the same age definition of precocious puberty for white and black girls yields a higher incidence in black girls.^{[4, 11]} No current evidence shows that black boys mature earlier than white boys; thus, incidence of precocious puberty among boys is similar in both races. The NHANES III study indicated that Mexican-American girls start breast development at a similar age as white girls, and that pubic hair appears slightly later.^[11]

Sex

In a series of more than 200 patients evaluated at a single medical center, central precocious puberty occurred 5 times more often in girls than boys.^[12] Idiopathic central precocious puberty occurred 8 times more often. A possible explanation for this difference is that many girls whose puberty is considered precocious are actually healthy girls at the early end of the normal distribution.

Age

If precocious puberty in females (mostly central) is defined as the early onset of breast development, then the data of Herman-Giddens et al can be used to estimate frequency of central precocious puberty at different ages in both white girls and black girls. Be cautious, however, in equating breast development in 3-year-olds with central precocious puberty because most such girls actually have premature thelarche, a benign normal variant (see Differentials). The younger the age of girls with proven central precocious puberty, the higher the likelihood of serious underlying disorder.