Precocious Puberty

Updated: Nov 30, 2020
  • Author: Paul B Kaplowitz, MD, PhD; Chief Editor: Robert P Hoffman, MD  more...
  • Print
Overview

Practice Essentials

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 designated as precocious in girls younger than 8 years; however, studies have come to indicate that signs of early puberty (breasts and pubic hair) are often present in girls (particularly Black girls) between ages 6-8 years. For boys, onset of puberty before age 9 years is still considered precocious.

In central precocious puberty (CPP), which is gonadotropin-dependent, early maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis occurs, with the full spectrum of physical and hormonal changes of puberty.

Premature adrenarche and premature thelarche are two common, benign, normal variant conditions that can resemble true precocious puberty but that progress slowly or not at all. Premature thelarche refers to the isolated appearance of breast development, usually in girls younger than 3 years; premature adrenarche refers to the 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 to distinguish these normal variants from true sexual precocity. A review of this topic was published as an American Academy of Pediatrics clinical report. [1]

Signs of precocious puberty

Precocious puberty in girls is characterized as follows:

  • The first and most obvious sign of early puberty is usually breast enlargement, which may initially be unilateral
  • Pubic and axillary hair may appear before, at about the same time as, or well after the appearance of breast tissue; axillary odor usually starts about the same time as the appearance of pubic hair
  • Menarche is a late event and does not usually occur until 2-3 years after onset of breast enlargement
  • The pubertal growth spurt occurs early in female puberty and usually is evident by the time of initial evaluation

Precocious puberty in boys is characterized as follows:

  • The earliest evidence of puberty is testicular enlargement, a subtle finding that often goes unnoticed by patients and parents
  • Growth of the penis and scrotum typically occurs at least a year after testicular enlargement
  • Accelerated linear growth (the pubertal growth spurt) occurs later in the course of male puberty than in female puberty but often takes place by the time other physical changes are noted

Workup in precocious puberty

Because of the development of more sensitive third-generation assays for luteinizing hormone (LH), which can detect levels as low as 0.1 IU/L or lower, random LH is now considered a good screening test for CPP, with levels of 0.3 IU/L or above considered diagnostic. However, many children with CPP have prepubertal basal LH levels but will respond to a challenge with gonadotropin-releasing hormone (GnRH) with an increase to 5 IU/L or above, which is considered pubertal.

Measurement of serum testosterone is useful in boys with suspected precocious puberty. Testosterone levels less than 30 ng/dL are in most cases prepubertal, while testosterone levels of 30-100 ng/dL are usually seen in cases where puberty is progressive and levels of greater than 100 ng/dL need further evaluation. For girls, estradiol measurements are usually elevated but are less reliable indicators of the stage of puberty.

Levels of adrenal androgens (eg, dehydroepiandrosterone [DHEA], DHEA sulfate [DHEA-S]) are usually elevated in boys and girls with premature pubarche. DHEA-S, the storage form of DHEA, is the preferred steroid to measure because its levels are much higher and vary much less during the day. In most children with premature pubarche, DHEA-S levels are 20-100 mcg/dL, whereas in rare patients with virilizing adrenal tumors, levels may exceed 500 mcg/dL.

When used to determine bone age, radiography of the hand and wrist is a quick and helpful means of estimating the likelihood of precocious puberty and its speed of progression.  A bone age advanced by 2 years relative to chronologic age is considered significant.

Magnetic resonance imaging (MRI) is often recommended to look for a tumor or hamartoma after hormonal studies indicate a diagnosis of CPP but is very unlikely to reveal pathology related to CPP in girls between the ages of 6 and 8 years.

If the history, physical examination, and laboratory data suggest that a child exhibits early and sustained evidence of pubertal maturation, the clinician must differentiate CPP from precocious pseudopuberty. In CPP, which is gonadotropin-dependent, early maturation of the entire hypothalamic-pituitary-gonadal (HPG) axis occurs, 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 the evaluation and treatment of patients with precocious pseudopuberty are quite different from those of patients with CPP.

Management

Early onset of puberty can cause several problems. The early growth spurt initially can result in tall stature, but rapid bone maturation can cause linear growth to cease too early and may 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. However, not all patients with CPP who are age 7 years or older at the time of onset require treatment. For patients with precocious puberty who are treated with GnRH agonists:

  • Follow-up should occur every 4-6 months to ensure that progression of puberty has been arrested
  • Favorable signs include normalization of accelerated growth, reduction (or at least no increase) in breast size, and suppression of gonadotropin levels after a challenge of GnRH
  • The ideal testing frequency has not been established
  • Monitor bone age yearly to confirm that advancement has slowed
Next:

Pathophysiology

High-amplitude pulses of GnRH from the hypothalamus at the onset of puberty cause pulsatile increases in the pituitary gonadotropins 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. Research has implicated a family of peptides called kisspeptins, produced in the central nervous system (CNS), in the regulation of GnRH secretion.

The hypothesized mechanisms that suppress the onset of puberty in early childhood 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.

Most patients, particularly girls suspected of having CPP, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve. CNS imaging studies of these girls aged 6-8 years usually reveal no structural abnormalities. While older studies reported a significant proportion of abnormal findings such as tumors, subsequent reports have found an incidence of clinically significant brain imaging findings of less than 1%, even in girls below age 6 years. [2]  Abnormal computed tomography (CT) or MRI scans are more frequent among boys with CPP than among girls with the condition.

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)
Previous
Next:

Epidemiology

Frequency

The frequency of findings suggestive of precocious puberty in girls and boys depends on whether one is looking at genital hair or breast development, as well as the age at which the condition is considered precocious. The prevalence also depends on whether one is doing population-based screening or assessing the number of patients who are referred to specialists for evaluation. One of the very few studies looking at the prevalence and incidence of precocious puberty based on a national patient register was a Danish report covering the period 1993-2001. The investigators estimated the prevalence at about 0.2% of girls (0.8% for girls ages 5-9 years) and less than 0.05% of boys. [3] This is far lower than indicated in the studies noted below, which are based on the examination of larger groups of children.

United States

In 1969, Marshall and Tanner published the results of their study of 192 White British girls, stating that the average age of thelarche was 11 years and defining precocious puberty in girls as commencing before age 8 years. [4] 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 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. [5]  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.

In 1999, as a result of the Herman-Giddens study, 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. [6]  However, most clinicians continue to use the 8-year definition.

In 2010, a study by Biro et al reported that in a cohort of 1239 girls aged 7-7.99 years from three urban centers, the proportion who had reached Tanner 2 breast development was 10.4% of White girls, 23.4% of Black girls, and 14.9% of Hispanic girls. [7]  While this was a cross-sectional study, the results confirmed that in the United States, the appearance of breast development prior to age 8 years is quite common. Follow-up of this cohort has indicated that none of these apparently early maturing girls were actually diagnosed with and treated for CPP (Biro F, personal communication, 2020). This suggests that the majority of girls who have breast development before age 8 years do not have the rapidly progressive form of CPP, which requires treatment.

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. [8]

International

A 2003 review of trends in timing of puberty around the world showed no clear progression toward earlier puberty in northern Europe. However, earlier mean age of menarche has been reported in some southern European countries and other warmer parts of the world. [9]  A Danish study 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). [10]  A study of over 20,000 girls from urban China performed from 2003-2005 showed 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 girls aged 8 years already had evidence of breast development. [11]  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 females. Similarly, a literature review by Eckert-Lind et al indicated that worldwide, from 1977 to 2013, the mean age of thelarche fell by a mean of nearly 3 months per decade. The investigators therefore state that at least in some parts of the world, precocious puberty needs to be redefined. [12]

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 internationally adopted girls was significantly lower than that observed in a reference group of Danish-born girls. [13]  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 suggests that their earlier puberty is centrally mediated and not chemically induced. A commentary published in 2013 suggested that frequent underreporting of age of adoptees from certain countries such as China may be the real explanation for this phenomenon. [14]

Mortality/Morbidity

Isolated sexual precocity of unknown etiology carries no increased risk of mortality; however, distinguishing between children with idiopathic CPP and the rare patient with a CNS, an adrenal, or an ovarian tumor is important because the latter group may be at risk for tumor-related complications. Moreover, some studies have found an association between early puberty in girls and a higher risk of breast cancer. [15]

Children with precocious puberty may be stressed because of physical and hormonal changes that they are too young to understand and may be teased by peers because of their physical difference. Girls who reach menarche before age 9-10 years 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. In girls with a history of early puberty, initiation of sexual activity may occur at a slightly earlier age than usual.

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, with the result being that children with this condition may initially be considerably taller than their peers. Because bone maturation is also accelerated, however, 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 CPP 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/ethnicity

The study by Herman-Giddens et al, as well as data from a National Health and Nutrition Examination Survey (NHANES) III report and a study by Biro et al, conclusively showed that Black females in the United States have onset of breast development and pubic hair about 1 year earlier than White girls. Thus, using the same age definition of precocious puberty for White and Black females yields a higher incidence in Black girls. [5, 16, 17]  No current evidence shows that Black males mature earlier than White ones; thus, the incidence of precocious puberty among boys is similar in both races. The NHANES III study found that Mexican-American girls start breast development at a similar age as White girls and that pubic hair appears slightly later, [16] while the study by Biro et al indicates that Hispanic girls fall between Black and White females in the age of onset of breast development.

Sex

In a series of more than 200 patients evaluated at a single medical center, CPP occurred five times more often in girls than boys; [18] idiopathic CPP occurred eight 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.

Previous
Next:

Prognosis

Without treatment

Most girls who are aged 6-8 years at the onset of puberty achieve an adult height within the normal range or appropriate for their genetic potential. [19, 20] This is because most such girls are significantly taller than average at the time of diagnosis, and thus early cessation of growth typically brings their height into, but not below, the normal range.

Consider therapy following initial evaluation for girls who have predicted heights of less than 4 ft 11 in or who are well below their target height (ie, average of parents' heights, less 2.5 in), when the patient also has very advanced bone age, a height below the 25th percentile, or both.

Controversy surrounds the significance of several studies (mostly with small numbers of patients and no control group) that appear to indicate that girls with CPP are at increased risk for significant behavior problems, such as poor self-esteem and higher anxiety, irritability, or withdrawal. Other studies, however, have no shown such problems. A review of this topic by Walvoord and Mazur concluded that CPP may become a risk factor for psychosocial problems, mainly in the setting of other risk factors, but they cautioned against medical therapy as a means of avoiding presumed negative psychological consequences of precocious puberty. [21]

In a study of 36 girls with signs of early puberty, including 15 patients with CPP, eight with premature adrenarche, and 13 with early normal puberty, GnRH agonist treatment was administered to all girls with CPP. Normal findings were seen, on average, for baseline psychological assessments of cognitive competence, peer acceptance, physical competence, and maternal acceptance. At 1-year follow-up, results were “largely reassuring regarding concerns of adverse psychological consequences of early puberty in girls.” [22]

With treatment

Most studies show significant improvement in adult height compared with height predicted at the start of therapy, but the extent of this improvement depends to some extent on the age of onset of CPP. [23] For example, a study from Israel showed that height gained in girls after discontinuation of GnRH analogue therapy at age 11-12 years (and bone age of 12-12.5 y) is greater for girls with onset of CPP before age 6 years than at age 6-8 years or after age 8 years. Mean adult height was better than genetic target height in the younger group and was less than target height in the group whose puberty started after age 8 years. [24]  This indicates that the benefit of treatment in terms of increased adult height is the greatest in patients who are diagnosed with CPP and started on GnRH analogues at younger ages. The lack of effect in the older girls was confirmed by a meta-analysis showing that treatment of mildly early puberty in girls (onset between ages 8 and 9 y) did not improve adult height. [25]

A review of the effects of GnRH analogue on adult height highlighted several problems with assessing outcomes. These include (1) a paucity of well-designed, randomized, controlled studies, and (2) problems in accurately estimating predicted height based on bone age readings, which may be differently interpreted by different readers. A table in this review summarizing 29 studies from 1994-2015 with differing patient populations found that the mean value for adult height after treatment minus predicted adult height based on bone age varied widely from 2-10 cm. [26]

Previous
Next:

Patient Education

Patient resources that may be helpful include the following publications:

Previous