Normal onset of puberty
Have definitions of onset changed?
Sasmira Lalwani, MD a
, *
Richard H. Reindollar, MD a,b
Ann J. Davis, MD a,b
a Division
of Reproductive Endocrinology and Infertility
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215, USA
b Department
of Obstetrics and Gynecology
Harvard Medical School
Boston, MA 02215, USA
|
* Corresponding author |
|
This article was originally |
|
PII S0889-8545(03)00025-1 |
Puberty is the sequence of events in an individual’s life that culminates in
physical, sexual, and emotional maturation. This sequence of events is caused
by the maturation of the hypothalamic-pituitary-gonadal (HPG) axis.
Maturation begins with a significant rise in gonadotropin secretion during
fetal life that persists during infancy and goes into a quiescent phase during
childhood. The onset of puberty results from the episodic release of
luteinizing hormone (LH) and follicular stimulating hormone (FSH). This release
reflects the intermittent release of GnRH from the hypothalamus in greater
quantities and more frequent pulses.
The physiology of puberty
The fetal, infancy, and childhood period
By 10 weeks of gestation, GnRH is
present in the hypothalamus and functionally active after 20 weeks of
gestational age [1]
, and the pituitary responds to GnRH stimulation by secreting LH and
FSH. GnRH and gonadal secretion progressively increase and stimulate gonadal
maturation and hormone production. At birth, the levels of gonadotropins and
sex steroid hormones are high, but they decline after a few days. In response
to the decline in circulating sex steroids originating from the placenta, the
gonadotropin levels start to rise again during the first week of life. During
the next several weeks, levels of gonadotropins and gonadal hormones continue
to be higher than the levels in older children. This suggests that the gonads
are responsive to stimulation and are fully functional. Gonadotropins and sex
steroids peak at 2 to 3 months of age, after which they drop to low levels for
many years. The fall in gonadotropin levels occurs not only because of an
adjustment in the negative feedback mechanism but also because of probable
Central Nervous System (CNS) control of gonadotropin secretion (this fall in
gonadotropin levels also is seen in agonadal children). Even though
gonadotropin levels are lowest during mid-childhood, measurable amounts of
gonadotropin are present, indicating some amount of episodic release [2]
. Hence, a small amount of sex steroids, including estrogen, may be
present in some children [3]
.
Puberty
Gonadotropin-releasing hormone and gonadotropins
The HPG axis is active in fetal
life, and the pituitary and gonads are ready to respond with the appropriate
stimulation by GnRH and the gonadotropins, respectively. Control is at the
level of GnRH stimulation or a higher CNS loci. Preceding the onset of and
during puberty, the mean levels of the gonadotropins rise, reflecting the increased
episodic release of gonadotropins in response to pulsatile GnRH secretion. Due
to this alteration in GnRH secretion, gonadotropin secretion is enhanced. A low
level of gonadotropin secretion, with a low frequency and amplitude that
increase during sleep, is present in prepubertal children [1]
[2]
[3]
[4]
[5]
. As pubertal maturation progresses, the frequency and amplitude of
these pulses increase. During early puberty, these pulses are seen more
frequently during sleep than in the wakeful state. These change are more
dramatic for LH than for FSH, with the rise in LH being greater than FSH during
puberty [6]
. In adults, the episodic rise in LH occurs every 90 minutes and lasts
for approximately 20 minutes. The episodic release of FSH occurs less
dramatically and is greater during sleep. These episodic phenomena are produced
by the maturation of the CNS-stimulating influences that affect the GnRH pulse
generator. Thus, pubertal change of the hypothalamus and the pituitary involves
the increase of GnRH, LH, and FSH pulsatile secretion rather than the onset of
secretion. The secretion of GnRH (12–18 times every 24 hours) is regulated by a
region in the arcuate nucleus of the medial basal hypothalamus. At the onset of
puberty, GnRH stimulation exerts a priming effect on the pituitary and causes a
progressive increase in gonadotropins. This increased responsiveness also is
accompanied by an increase in GnRH receptors in the pituitary.
Adult levels of LH and FSH are
regulated by gonadal hormone secretion through a negative feedback mechanism
and in the middle of the menstrual cycle through a positive feedback mechanism.
Sex steroids
The rise of gonadotropins and of
sex steroids from the gonads and the adrenal cortex occurs before the onset of
puberty. The increase in adrenal androgen production, or adrenarche, is
responsible for the onset of pubic hair growth (pubarche). The increase in
gonadal sex steroid production is known as gonadarche.
Adrenarche . The adrenal androgens may be the first hormones
to be elevated in puberty. The appearance of pubic and axillary hair, acne, and
body odor may be the result of adrenal androgen production since these findings
can occur without the presence of gonadal steroids and before any other signs
of pubertal development.
The cause of adrenarche is not
known. Elevated gonadotropin secretion does not cause an increase in
adrenocorticotropic (ACTH) secretion. ACTH levels also do not increase at
adrenarche; however, the response of the adrenal steroids to ACTH changes. The
androgens are more sensitive to ACTH stimulation than the other adrenal
steroids, and this response parallels the development of the adrenal zona
reticularis.
Gonadarche . Gonadarche occurs due to the elevation in
circulating gonadal steroids, especially estrogens in girls, in response to
gonadotropin stimulation.
Other factors influencing the onset of puberty
Leptin, a hormone derived from
adipose tissue, plays a role in body composition. It is hypothesized that body
mass and composition regulate the onset of puberty. Because leptin levels rise
during puberty, there is considerable interest in the role of leptin in the
onset of puberty [7]
[8]
.
Activin and Follistatin are two
other hormones that regulate follicular maturation and atresia. Although the
levels of these hormones do not change during puberty, they do change during
adulthood [9]
.
Other factors, such as excessive
exercise, inadequate nutrition, and psychiatric illnesses (eg, anorexia
nervosa), are associated with hypogonadotropic states that alter the onset of
puberty.
Genetic regulation of the timing of
puberty is seen in a correlation between the ages at which a mother and
offspring attain pubertal milestones [10]
. Studies of twins demonstrate that pubertal milestones display more
similarity between monozygotic twins than dizygotic twins [11]
[12]
[13]
[14]
.
Patterns of onset: have definitions changed?
The pubertal sequence of events
follows a certain pattern. Usually the first sign is accelerated growth,
followed by breast development, adrenarche, and menarche. This sequence of
events on average requires a period of 4.5 years (range 1.5–6 years). Pubertal
development has started occurring earlier, partly due to better socioeconomic
conditions, especially nutritional status. Racial differences do exist in the
onset and progression of puberty, with secondary sexual characteristics
developing earlier in African-American girls than in white girls.
Previously, it was accepted that
normal puberty in girls does not begin before 8 years of age. In 1997, the
American Academy of Pediatrics published a cross-sectional study of pubertal
development in American girls who were seen in pediatric office practices. This
large multicenter study of 17,077 girls consisted of 90.4% white Americans and
9.6% black Americans [10]
. Table
1 contains the important findings of the study.
|
Table 1. Cross-sectional study of |
||
|
Abbreviations: y, years. |
||
|
Pubertal event |
Black American girls |
White American girls |
|
Breast or pubic hair |
||
|
Age 7 y |
27.2% |
6.7% |
|
Age 8 y |
48.3% |
14.7% |
|
Menarche |
||
|
Age 11 y |
27.9% |
13.4% |
|
Age 12 y |
62.1% |
35.2% |
|
Thelarche (mean age) |
8.87 y |
9.96 y |
|
Adrenarche (mean age) |
8.78 y |
10.51 y |
|
Menarche (mean age) |
12.16 y |
12.88 y |
The data revealed that the
prevalence of breast or pubic hair before 8 years of age was 27% in black girls
and 7% in white girls. By 9 years of age, 48% of black girls and 15% of white
girls showed some sign of pubertal development. The mean age of menarche—12.2
years in black girls and 12.9 years in white girls—did not differ significantly
from other reports. This study suggests that even though puberty is occurring
earlier than previously thought, menarche is not occurring earlier and puberty
is not completed earlier. In girls who showed an earlier onset of puberty,
growth may be taking place at a slower pace or initial breast development may
not be associated with the onset of real puberty. Maybe this earlier onset can
be attributed to a different subset of the population, which influenced the
overall data. A contributing factor could be that these data are derived from
office practices instead of a random sampling of the population.
As a result of this study, new
guidelines were recommended to redefine precocious puberty in girls from the
onset of breast development before 8 years of age to the onset of breast or
pubic hair before 7 years of age in white girls and 6 years of age in black
girls [11]
. We should be cautious in redefining the onset of puberty based on one
study. Precocious puberty can be the result of a serious disorder, and
diagnosis involves more criteria than age. Puberty that progresses so rapidly
that growth and development are clearly excessive for age should be evaluated
and therapy to suppress pubertal development should be considered.
Stages of pubertal development
In general, the first sign of puberty
is an acceleration of growth followed by breast budding. Breast development
follows a series of events, with adrenarche usually following thelarche by 2
years. In some cases the sequence may be reversed, with pubic hair being the
first sign of puberty in approximately 20% of girls. Menarche is a late event
that occurs during deceleration of the growth phase. About 90% of menstrual
cycles may not be ovulatory until 6 to 7 years after menarche. Table
2 outlines the mean developmental pattern of puberty in girls [10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
.
|
Table 2. Sequence of pubertal |
|
|
Pubertal event |
Mean age |
|
Breast development (Tanner stage 2) |
10.0–10.5 |
|
Pubic hair growth (Tanner stage 2) |
10.3–10.8 |
|
Maximum growth rate |
11.2–11.7 |
|
Maximum rate of weight gain |
11.7–12.2 |
|
Breast development (Tanner stage 3) |
11.3–11.8 |
|
Pubic hair growth (Tanner stage 3) |
11.4–11.9 |
|
Onset of axillary hair |
12.3–12.8 |
|
Menarche |
12.6–13.1 |
|
Breast development (Tanner stage 4) |
12.5–13.0 |
|
Pubic hair growth (Tanner stage 4) |
12.5–13.0 |
|
Regular menses |
13.7–14.2 |
|
Breast development (Tanner stage 5) |
14.0–14.5 |
|
Pubic hair growth (Tanner stage 5) |
14.0–14.5 |
The following sections describe the
stages of pubertal development:
|
|
Growth and skeletal maturation |
|
|
Thelarche (breast development) |
|
|
Adrenarche |
|
|
Menarche |
Growth and skeletal maturation
In girls, the growth spurt occurs
early compared with boys and occasionally precedes thelarche. Peak growth
occurs when breast development is between Tanner stages 2 and 3. Sex steroids,
especially estrogen, play an important role in the skeletal growth that occurs
during puberty in both women and men. Estrogen is a potent stimulator of bone
growth, and it is necessary for the closure of the epiphysis. Individuals with
aromatase deficiency or estrogen receptor mutations continue to grow into
adulthood and become very tall [14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
. Estrogen also plays a critical role in the accumulation of bone mass,
with peak bone mass attained late in puberty. Besides estrogen, the presence of
growth hormone and insulin-like growth factor-I are necessary for growth [22]
.
Thelarche
The average of onset of breast
budding is approximately 10 years of age and reflects the progressive increase
in estrogen stimulation and production. Breast development follows a
well-recognized sequence of events characterized by the following Tanner stages
[23]
:
|
|
Absence of breast bud |
|
|
Presence of breast bud only |
|
|
Enlargement of entire breast mound |
|
|
Secondary areolar mound on top of the primary mound |
|
|
Adult mature breast contour, secondary mound no longer |
Adrenarche
The appearance of pubic hair is the
next change seen in puberty. The texture of the pubic hair is longer and
coarser than the body hair of childhood. Pubic hair development, which reflects
increased androgen production, is characterized by the following Tanner stages [23]
.
|
|
Nonsexual, general body hair |
|
|
Long, coarse, pigmented hair, usually appearing along the |
|
|
Greater concentration of coarse, long hair extending to |
|
|
Abundance of coarse, dark pubic hair on the mons and labia |
|
|
Pubic hair present in an adult pattern, an inverted |
Menarche
The mean interval between breast
budding and the onset of menses is approximately 2 years. This may vary: the
earlier the thelarche, the longer until menarche [24]
. Menarche depends on hormonal levels during early puberty, with higher
levels leading to an earlier onset [25]
. Menarche most commonly occurs during stage 3 or 4 of breast
development.
The median age of the onset of
menses in American girls is 12.8 years (range of 9.1–17.7 years) [13]
[26]
. The menses following menarche are usually anovulatory, with 25% to 50%
of girls anovulatory 4 years after menarche [27]
[28]
.
Menarche occurs after the growth
spurt has passed. Slower growth (on average, 6 cm or 2.4 in) occurs after
menarche.
Variations
Variation in the duration of
pubertal development represents diversity in the rate of maturation and
attainment of full reproductive function. Complete breast development can take
3 years or longer, with 3 to 4 years required for pubic hair development.
Prepubertal development of sexual hair as an isolated event is known as
premature pubarche, and isolated breast development is known as premature
thelarche. Both can represent the onset of precocious puberty; however, once
precocious puberty is ruled out, these events by themselves are innocuous.
Summary
Puberty is the sequence of events
that culminates in the ability to procreate. It is widely accepted that the
onset of puberty in girls occurs on average at 8 years of age and that onset
prior to 8 years of age is precocious puberty. As a result of the
cross-sectional study by the American Association of Pediatrics, a movement
exists to change the age limit of the onset of puberty to 6 years of age in
black girls and 7 years of age in white girls. We should be cautious in
adhering to strict age limits when diagnosing precocious puberty. Also the rapidity
and progression of puberty should be evaluated, and if appropriate, therapy to
suppress pubertal development considered.
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