Puberty—Timing is everything!

Puberty—Timing is everything!
BELINDA PINYERD, PhD, RN
Central Ohio Pediatric Endocrinology and Diabetes Services
Columbus, OH
WILLIAM B. ZIPF, MD, FAAP
Central Ohio Pediatric Endocrinology and Diabetes Services
Columbus, OH
BWResearch@columbus.rr.com
T: 614/840-0535
F: 614/840-0536
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ABSTRACT
Puberty is a dynamic period of physical growth, sexual maturation, and psychosocial
achievement that generally begins between age 8 and 14 years. The age of onset varies as a
function of gender, ethnicity, health status, genetics, nutrition, and activity level. Puberty is
initiated by hormonal changes triggered by the hypothalamus. Children with variants of
normal pubertal development—both early and late puberty—are common in pediatric
practice. Recognizing when variations are normal and when referral for further evaluation is
indicated is an important skill.
INTRODUCTION
"When it's time to change, you have to rearrange." - Peter Brady
“Puberty,” derived from the Latin pubertas meaning adulthood, is not a de novo event but a
process leading to physical, sexual, and psychosocial maturation (Blondell, Foster & Dave
1999). “Puberty” differs from “adolescence” in that it is just one change (maturation of the
reproductive system) that occurs during adolescence. From a biological perspective, puberty
is the stage of development during which an individual first attains fertility and is capable of
reproduction. Physical changes that occur during puberty include somatic growth, primary
sexual organ development (gonads and genitals), and the appearance of secondary sexual
characteristics (breasts and pubic hair). This paper reviews the hormonal processes
responsible for inducing puberty, clinical indicators and staging of normal puberty, and
psychosocial changes that accompany the physical maturation. Abnormal puberty patterns
and guidelines for assessment are also reviewed.
OVERVIEW: REGULATION OF PUBERTY
In normal puberty, hormone secretion changes dramatically. Central to the process is a
section of the brain called the hypothalamus, which produces a substance called gonadotropin
releasing hormone (GnRH). During childhood, GnRH secretion is minimal but with the onset
of puberty, secretion of GnRH is enhanced. The primary function of GnRH is to regulate
the growth, development, and function of the testes in the male and the ovaries in the
female. GnRH signals the pituitary gland to secrete luteinizing hormone (LH) and folliclePage 2 of 17
stimulating hormone (FSH) (also known as “gonadotropins”). In boys, LH stimulates
testosterone production and FSH promotes sperm production. In girls, both LH and FSH
are necessary for ovulation (rupture of follicle and release of egg from the ovary) while FSH
stimulates development and maturation of a follicle in one the ovaries
HORMONAL CHANGES
Two processes contribute to the physical manifestations of puberty: gonadarche, the ovary or
testes component of puberty; and adrenarche, the adrenal gland component of puberty. These
two components may seem to occur simultaneous and be a consequence of the same
phenomena, but they are separate and distinct events.
Gonadarche is initiated by cells of the hypothalamus that secrete GnRH. During childhood,
prior to the onset of puberty, the hypothalamus “gonadostat” is exquisitely sensitive to very
low concentrations of sex steroids (androgens and estrogens). As a result, GnRH secretion is
suppressed, preventing LH and follicle-stimulating hormone FSH release from the pituitary.
At the end of childhood, the hypothalamus is released from the suppressive effects of the
sex steroids, resulting in increased GnRH release and increased release of LH and FSH. In
boys, LH stimulates testosterone production and FSH supports sperm maturation. In girls,
FSH and LH stimulate ovary production of estrogen, progesterone, and testosterone, all
necessary for normal menstruation (Lee, 2003).
Adrenarche can occur separate from and without other signs of sexual development. The
physical signs of adrenarche include the development of adult body odor, increase in
testicular size, and early changes in body growth, axillary hair growth, and development of
pubic hair (pubarche). Biochemically, adrenarche actually begins earlier then these signs.
Studies have shown that in both boys and girls at approximately six years there is an increase
production of adrenal hormones by the adrenal gland. The stimulus of adrenarche has not
yet been determined, but it is separate from the onset of pituitary secretion of LH and FSH
(Lalwani, Reindollar & Davis, 2003).
While adrenarche begins biochemically in boys and girls at the same time, pubarche (onset of
sexual hair development.) occurs 6 to 12 months later in boys than girls. In females, the signs
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of adrenarche occur approximately six to 12 months after the onset of gonadarche.
Physically, it is observed that shortly after the onset of the first signs of breast development
(a sign of ovarian estrogen secretion), a young girl will then show signs of adrenal androgen
secretion. For some girls, this sequence is reversed. Recently there is greater attention being
given to this component of puberty because abnormalities in the timing of adrenarche have
been shown to be associated with irregular menstrual cycles, obesity, insulin resistance, and
increased risks for diabetes (Ibanez et al, 1998). In boys, the physical signs of adrenarche
cannot be distinguished from the signs of gonadarche. However, the presence of pubarche,
without a change in testicular size, is usually a sign that gonadarche has not yet begun.
STAGING AND TIMING
The pubertal sequence of events follows a certain pattern (accelerated growth, breast
development, adrenarche, menarche) on average requiring a period of 4.5 years (range 1.5–6
years), with girls beginning puberty earlier than boys. In fact, most information available
about the timing of puberty is for girls, as breast development and onset of menstruation
(menarche) are more overt and recordable than changes in penis and testicle size in boys.
Several factors in addition to gender and ethnicity impact the timing of puberty, including
genetics, dietary intake, and energy expenditure. Genetic factors play an important role, as
illustrated by the similar age of menarche in members of an ethnic population and in
mother-daughter and sibling pairs (Meyer et al., 1991). Type of protein consumption (animal
versus vegetable), amount of dietary fat, and total calories has also been related to onset of
puberty (Grumbach & Styne, 2003). Puberty often begins earlier in heavier children of both
sexes (Qing & Karlberg, 2001), whereas excessive exercise and psychiatric illnesses (eg,
anorexia nervosa) are associated with hypogonadotropic states that can delay or arrest the
onset of puberty (Warren & Vu, 2003).
What specifically triggers the onset is still debated. The attainment of a particular proportion
of fat mass has long been argued to be requisite for the onset of puberty in girls (Plant,
2002). Interest in this theory has intensified recently as a result of delayed puberty noted in
athletic girls and girls with eating disorders (Georgopoulos et al., 1999; Warren & Fried,
2001).
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Females
The first visible sign of sexual maturation is the appearance of “breast buds,” generally
around age 10 or 11 years of age. Full breast development takes 3 to 4 years, and is generally
complete by 14 years of age. In approximately 20 percent of girls, pubic hair may be the first
sign of puberty (Lalwani, Reindollar & Davis, 2003). As mentioned, pubic and axillary hair
growth is primarily due to a pubertal increase in adrenal androgen (adrenarche). Over the
next three years, the pubic hair becomes darker, curlier, and coarser, and spread to cover a
larger area. Hair also develops under the arms, on the arms and legs, and to a slight degree
on the face.
The most dramatic sign of sexual maturity in girls is the onset of menstruation, which usually
occurs at an average age of 12.8 years (range 11–13). Initial menstrual cycles are usually
anovulatory, which is associated with irregular and often painful periods. After
approximately one to two years the menstrual cycles become ovulatory and more regular
(Zacharias, Rand & Wurtman, 1976.
Males
For boys, an increase in testicular size occurs at 9.5–13.5 yr (average 12 yr) of age, which is
followed by the growth of pubic hair (Marshall & Tanner, 1970). The testes and scrotum
begin to grow, and the scrotum thins, darkens, and becomes pendulous. The penis lengthens
and widens, taking several years to reach full size. Sperm production coincides with testicular
and penile growth, generally occurring at age 13.5–14 years. Facial hair appears about three
years after the onset of pubic hair growth, first in the mustache area above the upper lip, and
later at the sides of the face and on the chin. The density and distribution of hair growth
varies considerably among adult men, and is correlated more with genetic factors than with
hormone levels (Lee, 2003). Gynecomastia (visible breast tissue) occurs in approximately
two-thirds of males some time during puberty. Onset may coincide with the onset of puberty
but primarily begins at ages 13–14, before testosterone levels have reached adult levels. Most
commonly it persists for 18–24 months then regresses by age 16 years (Zosi et al., 2002).
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OTHER PHYSICAL AND PSYCHOLOGICAL CHANGES
Growth Spurt
During puberty females and males experience a growth velocity greater than at any postnatal
age since infancy. The pubertal growth spurt in girls is usually observed along with the first
signs of puberty (breast development and pubic hair). Peak growth occurs when breast
development is between Tanner stages 2 and 3. Because girls reach peak height velocity
about 1.3 years before menarche, there is limited growth potential after menarche; most girls
grow only about 2.5 cm in height after menarche although there is a variation from 1 to as
much as 7 cm (Grumbach & Styne, 2003). In contrast to females, the peak growth spurt in
males occurs during midpuberty (Tanner stages 3–4), when testosterone levels are rapidly
rising. Peak growth velocity in boys is generally at 14–15 years of age. Boys attain 28 to 31
cm of growth during the pubertal growth spurt whereas girls attain 27.5 to 29 cm of growth
(Abbassi, 1998).
In both males and females, the ages at menarche and peak height velocity are not good
predictors of adult height because the duration of pubertal growth is the more important
determinant of final height. Nonetheless, extremely early onset of puberty can diminish
ultimate adult stature (Bourguignon, 1988) and prolonged delay of puberty (Hägg &
Juranger, 1991) can increase stature.
Acne
Comedones, acne, and seborrhea of the scalp appear as a result of the increased secretion of
gonadal and adrenal sex steroids. Early-onset acne correlates with the development of severe
acne later in puberty. Acne vulgaris, the most prevalent skin disorder in adolescence, occurs
at a mean age of 12.2 years ± 1.4 years (SD; range 9–15 years) in boys and progresses with
advancement through puberty. However, acne vulgaris can be the first notable sign of
puberty in a girl, preceding public hair and breast development.
Mood and depression
During puberty young girls frequently exhibit a negative self-image. Prepubertal boys and
girls demonstrate an equal frequency of depression, although there is a more frequent
occurrence in girls at stage 3. This change in the prevalence of depression appears more
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related to serum sex steroid concentrations than to LH or FSH values or the physical
changes of puberty (Angold, Costello & Worthman, 1998). Reports of attempted suicide
increase sharply during puberty, and suicide now ranks fourth as a cause of death among 15-
to 19-year-olds (Larsen, 2003). A retrospective analysis showed that adolescents who actually
committed suicide during puberty had the onset of their depression in childhood or early
puberty, even though the act of suicide occurred later in puberty (Rao et al., 1993).
Body image
An important aspect of puberty is the development of body image. Body image is a person’s
inner conception of his/her physical appearance. As obvious from the previous discussion,
adolescence is a time of great physical and social change. Adolescents are critical and
embarrassed about their bodies during puberty, either because they are maturing too early,
too late, or they are not developing according to societal’s standards of “attractiveness.”
Adolescent girls appear to be particularly vulnerable to developing a negative body image,
especially if their bodies develop at a pace that differs from average (Rosenblum & Lewis,
1999). Adolescents with severe body image distortions are vulnerable to developing
psychiatric disorders that can have life-threatening consequences (Weinshenker, 2002).
Psychosocial changes
Puberty includes a profound social change from the sheltered, single-classroom environment
of elementary school to the multiple classrooms and teachers of middle school (Mayer &
Carter, 2003). There is exposure to new peers, often with different life experiences and
behavior patterns. Risk-taking behaviors often increase, including sexual precocity and
alcohol and cigarette abuse. In contrast to the concrete reasoning of childhood, the child
entering puberty develops maturing abstract thought and decision-making processes. Other
psychological and psychosocial changes that occur during this time include the ability to
absorb the perspectives or viewpoints of others, the development of personal and sexual
identity, the establishment of a system of values, and increasing autonomy from family
(Remschmidt, 1994).
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ABNORMAL PUBERTY
Although the average age at menarche (12.8 years) has not fallen much in the past 60 years,
recent data suggest that the lower age limit for normal pubertal (thelarche) onset is below the
threshold of 8 years that is cited in many texts. Before 1997, premature adrenarche was
defined as pubic hair developing in girls younger than 8 years old and boys younger than 9
years. However, the results of a large, cross-sectional study (Herman-Giddens, Slora &
Wasserman, 1997) suggest that the onset of puberty in girls is occurring earlier than previous
studies have documented, with pubic hair development appearing in white girls as young as 7
years (between 7–11 years) and in African American girls as young as 6 years (between 6–11
years). The timing of puberty is significant from a clinical standpoint given the observation
that early-maturing girls and late-maturing boys show more evidence of adjustment
problems than other adolescents (Graber et al., 1997). However, the definition of early
puberty remains “puberty that occurs prior to age 8 years in girls and nine years in boys”
(Saenger, 2003).
Early
The majority of children who show signs of puberty at a young age have no discernable
underlying pathology, particularly if they meet other criteria (see Table 1). Some physicians
order an x-ray to check that the skeletal age of the child is no more than 2.5 standard
deviations (typically about 2 years) above the chronological age. For boys younger than 9
years of age who have penile enlargement, scrotal thinning, and accelerated growth, a formal
evaluation is warranted.
TABLE 1. CRITERIA OF BENIGN PREMATURE
PUBERTY








Sparse to moderate development of pubic hair
Sparse or no growth of axillary hair
Mild or no acne
Minimal or no acceleration in growth rate
Mild apocrine body order
No lowering of voice
No breast or testicular enlargement
No clitoromegaly
Source: Nakamoto, 2000
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When puberty in a young child is driven by activation of hypothalamic GnRH secretion, it is
designated "central" or "true" precocious puberty (CPP). In a minority of patients, CPP
arises in the setting of a central nervous system (CNS) lesion (e.g. neurofibromatosis, hydro-
cephalus, CNS infection, and intracranial neoplasm with or without radiation therapy). CNS
lesions seem to predispose males and females equally to early central puberty; that is, the sex
ratio among patients with neurogenic CPP approximates unity. However, among children
with CPP in whom there is no underlying pathology (idiopathic CPP), there is a striking sex
difference, with the female to male ratio approaching 10:1 in most series (Palmert &
Boepple, 2001). From a psychosocial perspective, CPP is sometimes accompanied with
behavioral disturbances and symptoms of depression and/or anxiety. Dorn et al (1999)
reported more withdrawal, social problems, aggression, somatic complaints, and depression
in children with premature adrenarche as compared to children with “on-time” adrenarche.
Precocious puberty also places a child at risk for not achieving his/her genetic height
potential. The rapid maturation of the growth plate (due to sex steroid exposure) will often
result in temporary acceleration of linear growth, but the accompanying early closure of
growth plates results in early cessation of growth and ultimately shorter than would be
expected adult height (Lee, 1999).
Delayed
Delayed puberty describes the clinical condition in which the physical manifestations of
puberty start late (usually > +2.5 SD later than the mean). In the United States, puberty is
considered to be delayed if sexual maturation has not become apparent by age 14 years in
boys or age 13 years in girls. This clinical diagnosis also is made in the absence of menarche
by age 16 years or in the absence of menarche within 5 years of pubertal onset. Using these
criteria, approximately 2.5% of healthy adolescents will be identified as having pubertal delay
(Rosen & Foster, 2001). In most cases delayed puberty is not due to any underlying
pathology, but instead represents an extreme end of normal puberty, referred to as
constitutional delay of growth and maturation. When puberty does begin, it is entirely
normal. However, delayed puberty generally warrants referral to a pediatric endocrinologist
to rule out possible genetic, hypothalamic, pituitary, gonodal, or system conditions that
could be present.
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PUBERTAL ASSESSMENT
The standard clinical system for describing normal pubertal development and its variations is
the five-stage system (called “Tanner Staging”) developed by Marshall & Tanner (1969,
1970) (refer to Tables 2 & 3). Each stage represents the extent of pubic hair growth and
breast (female)/genitalia (males) development.
In girls, breasts and pubic hair must be staged separately (see Table 2). Tanner stage 2 is
characterized by small breast buds and "peach-fuzz" in the pubic area. During stage 3, breast
buds become larger and pubic hair growth continues, but it is mostly in the center and does
not extend out to the thighs or upward. Stage 4 is characterized by noticeable growth of
pubic hair, underarm hair growth, and the breasts take on a "mound" form. The first
menstrual period usually occurs sometime during the fourth or fifth stage. A girl has reached
Tanner stage 5 when her breasts are fully formed and her pubic hair is adult in quantity and
type, forming the classical upside-down triangle shape common to women. Rough estimates
based upon the size and shape of the breasts (see Figure 1) along with the amount and type
of hair present in the pubic area are the indexes used to track pubertal changes (Marshall &
Tanner, 1969).
In boys, pubertal hair distribution and testicular size must be staged separately (see Table 3).
In stage 1, there is no pubic hair growth, and the penis, testes, and scrotum are about the
same size and proportion as in early childhood. Stage 2 is characterized by "peach-fuzz" in
the pubic area, testicular enlargement, and scrotum growth, thinning and reddening. During
stage 3 the penis grows in length and pubic hair growth is darker and coarser. Stage 4 is
characterized by more pubic hair, darkening of the scrotum, and increased growth of the
penis. A boy has reached Tanner stage 5 when the genitalia are adult size and shape and his
pubic hair has spread to the medial thighs (Marshall & Tanner, 1970). During this time the
testes increase in volume from approximately 3 mL (prepubertal) to up to 20 mL (adult-
hood). The Prader orchidometer, which consists of a series of increasingly larger oval beads,
is the standard by which the practitioner makes a determination of the patient’s testicular
size (Styne, 2002).
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When a child presents with abnormal puberty, the goal of the initial assessment is to
distinguish benign constitutional causes from pathologic causes. The history should focus on
the child’s previous growth and development, including the timing and sequence of the
physical milestones of puberty. A history of medical or surgical treatment may provide clues
to an underlying pathologic condition. The family history may reveal information about a
familial pattern of delayed or early puberty, as well as information about genetic disease. A
physical examination should focus on evaluation of the genitalia and determination of the
stage of pubertal development. A detailed growth chart is used to estimate annual growth
rate (centimeters per year) and to determine if a growth spurt has occurred. When the history
and/or evaluation of the child with early or delayed pubertal development suggest a
pathological cause, referral to a pediatric endocrinologist is warranted.
CLINICAL IMPLICATIONS
Knowledge of the timing and the physical changes associated with puberty is important for
pediatric practitioners. Parents and adolescents often experience anxiety when puberty is not
occurring as expected, even when it occurs within the range of normal. The pediatric
practitioner can allay much of that anxiety with counseling regarding the natural and normal
variation of this process. A clear understanding of pubertal milestones also promotes
appropriate interventions for delayed or advanced puberty when the practitioner and parents
are in agreement that intervention is in the best interest of the child. Recently, changes in the
timing of puberty as compared to previously published standards now make the
understanding of this complex process even more important. The observation that more
children are showing signs of puberty earlier places pressure upon the practitioner to
differentiate the child with early but otherwise normal puberty from the child with early
onset puberty as a consequence of a pathologic process. Even with normal but early-onset
puberty, close observation of the temporal process is needed to adequately predict if the
abnormal timing will impact final adult height. Referral to a specialist in pediatric
endocrinology is indicated for patients who present with signs of early or delayed puberty.
Health care for adolescents should include systematic monitoring of pubertal development
and concerns in order to aggressively educate preadolescents to negotiate this period
smoothly and to avoid high-risk behaviors that could have negative health and social
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sequelae during adolescence and adulthood. Interventions with parents of children who
present with abnormal puberty include providing anticipatory guidance, supporting parent
communication strategies, and providing support and information resources (Doswell &
Vandestienne, 1996; Williams, 1995). Finally, with the observation that precocious
adrenarche can be an early sign of the metabolic syndrome, close monitoring for obesity,
insulin resistance, acanthosis nigracans, hypertriglyceridemia, and other problems associated
with the metabolic syndrome are particularly relevant when the child presents with signs of
early puberty.
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TABLE 2. TANNER STAGES OF FEMALE PUBERTY
STAGE
BREAST
1
PUBIC HAIR
Only papillae are elevated.
Vellus hair only and hair is similar to development
over anterior abdominal wall (ie. no pubic hair).
2
Breast bud and papilla are elevated and a small
mount is present; areola diameter is enlarged.
There is sparse growth of long, slightly pigmented,
downy hair or only slightly curled hair, appearing
along labia.
3
Further enlargement of breast mound; increased
palpable glandular tissue.
Hair is darker, coarser, more curled, and spreads to
the pubic junction.
4
Areola and papilla are elevated to form a second
mound above the level of the rest of the breast.
Adult-type hair; area covered is less than that in
most adults; there is no spread to the medial surface
of thighs.
5
Adult mature breast; recession of areola to the
mound of breast tissue, rounding of the breast
mound, and projection of only the papilla are
evident.
Adult-type hair with increased spread to medial
surface of thighs; distribution is as an inverse
triangle.
Preadolescent
Adult
FIGURE 1. DIAGRAMMATIC REPRESENTATION OF TANNER STAGES I TO V
OF HUMAN BREAST MATURATION
From Marshall WA, Tanner JM: "Variations in patterns of pubertal changes in girls." Archives of
Disease in Childhood 44:291-303, 1969; USED WITH PERMISSION???
Page 13 of 17
TABLE 3. TANNER STAGES OF MALE PUBERTY
STAGE
GENITAL STAGE
1
Testes, scrotum, and penis are
about the same size and
proportion as those in early
childhood.
Vellus over the pubes is no
further developed than that
over the abdominal wall, i.e.,
no pubic hair.
2
Scrotum and testes have
enlarged, and there is a change
in the texture of scrotal skin
and some reddening of scrotal
skin.
There is sparse growth of long,
slightly pigmented, downy hair,
straight or only slightly curled,
appearing chiefly at base of
penis.
3
Growth of the penis has
occurred, at first mainly in
length but with some increase
in breadth. There has been
further growth of the testes
and the scrotum.
Hair is considerably darker,
coarser, and more curled and
spreads sparsely over junction
of pubes.
4
The penis is further enlarged in
length and breadth, with
development of glans. The
testes and the scrotum are
further enlarged. There is also
further darkening of scrotal
skin.
Hair is now adult in type, but
the area covered by it is smaller
than that in most adults. There
is no spread to the medial
surface of the thighs.
5
Genitalia are adult in size and
shape. No further enlargement
takes place after stage 5 is
reached.
Hair is adult in quantity and
type, distributed as an inverse
triangle. There is spread to the
medial surface of the thighs
but not up the linea alba or
elsewhere above the base of
the inverse triangle.
Preadolescent
Adult
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PUBIC HAIR STAGE
REFERENCES
Abbassi V. (1998). Growth and normal puberty. Pediatrics, 102, 507-511.
Angold A., Costello E.J., & Worthman C.M. (1998). Puberty and depression: the roles of
age, pubertal status and pubertal timing. Psycholological Medicine, 28, 51-61.
Blondell R.D., Foster M.B., & Dave K.C. (1999). Disorders of puberty. American Family
Physician, 60, 209-224.
Bourguignon J.P. (1988). Linear growth as a function of age at onset of puberty and sex
steroid dosage: therapeutic implications. Endocrine Reviews, 9, 467-488.
Dorn L.D., Mitt S.F., & Rotenstein D. (1999). Biopsychological and cognitive differences in
children with premature vs. on-time adrenarche. Archives Pediatric Adolescent Medicine, 153,
137-146.
Doswell W.M., & Vandestienne G. (1996). The use of focus groups to examine pubertal
concerns in preteen girls: initial findings and implications for practice and research. Issues in
Comprehensive Pediatric Nursing, 19(2), 103-120.
Georgopoulos N., Markou K., Theodoropoulou A., Paraskevopoulou P., Varaki L., Kazantzi
Z., Leglise M., & Vagenakis A.G. (1999). Growth and pubertal development in elite female
rhythmic gymnasts. Journal of Clinical Endocrinology and Metabolism, 84(12), 4525-4530.
Graber J.A., Lewinsohn P.M., Seeley J.R., &Brooks-Gunn J. (1997). Is psychopathology
associated with the timing of pubertal development? Journal of the American Academy of Child
and Adolescent Psychiatry, 36(12), 1768-1776.
Grumbach M.M., & Styne D.M. (2003). Puberty: Ontogeny, neuroendocrinology,
physiology, and disorders. In Larsen P.R. (Ed.), Williams textbook of endocrinology, 10th ed, (pp
1115-1200). St. Louis: Saunders.
Hägg U., & Juranger J. (1991). Height and height velocity in early, average and late maturers
followed to the age of 25: a prospective longitudinal study of Swedish urban children from
birth to adulthood. Annals of Human Biology, 18, 47-56.
Hamann A., & Matthaei S. (1996). Regulation of energy balance by leptin. Experimental and
Clinical Endocrinology and Diabetes, 104, 293-300.
Herman-Giddens M.E., Slora E.J., Wasserman R.C., et al. (1997). Secondary sexual
characteristics and menses in young girls seen in office practice: a study from the Pediatric
Research in Office Settings Network. Pediatrics, 99, 505-512.
Ibanez L., Potau N., Francois I., & de Zegher F. (1998). Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth.
Journal of Clinical Endocrinology and Metabolism, 83, 3558-3562.
Page 15 of 17
Lalwani S., Reindollar R.H., & Davis A.J. (2003). Normal onset of puberty have definitions
of onset changed? Obstetrics and Gynecology Clinics of North America, 30(2), 279-286.
Lee P.A. (1999). Central precocious puberty: An overview of diagnosis, treatment, and
outcome. Endocrinology and Metabolism Clinics, 28(4), 901-908.
Lee P.A. (2003). Puberty and its disorders. In F. Lifshitz F (Ed.), Pediatric endocrinology, 4th ed
(pp. 221-237). New York: Marcel Dekker.
Marshall W.A., & Tanner J.M. (1969). Variations in pattern of pubertal changes in girls.
Archives of Disease in Childhood, 44(235), 291-303.
Marshall W.A., & Tanner J.M. (1970). Variations in the pattern of pubertal changes in boys.
Archives of Disease in Childhood, 45(239), 13-23.
Mayer C., & Carter J. (2003). Puberty advice for year 6 and 7 boys and girls. The Journal of
Family Health Care, 13(3), 70-72.
Meyer J.M., Eaves L.J., Heath A.C., & Martin N.G. (1991). Estimating genetic influences on
the age-at-menarche: a survival analysis approach. American Journal of Medical Genetics, 39, 148154.
Nakamoto J.M. (2000). Myths and variations in normal pubertal development. Western Journal
of Medicine, 172(3), 182-185.
Palmert M.R., & Boepple P.A. (2001).Variation in the timing of puberty: clinical spectrum
and genetic investigation. Journal of Clinical Endocrinology and Metabolism, 86, 2364-2368.
Plant T.M. (2002). Neurophysiology of puberty. Journal of Adolescent Health, 31(6 Suppl), 185191.
Qing H., & Karlberg J. (2001). BMI in childhood and its association with height gain, timing
of puberty, and final height. Pediatric Research, 49, 244-251.
Rao U., Weissman M.M., Martin J.A., & Hammond R.W. (1993). Childhood depression and
risk of suicide: a preliminary report of a longitudinal study. Journal of the American Academy of
Child and Adolescent Psychiatry, 32, 21-27.
Remschmidt H. (1994). Psychosocial milestones in normal puberty and adolescence. Hormone
Research, 41(suppl 2), 19-29.
Rosen D.S., & Foster C. (2001). Delayed puberty. Pediatrics in Review, 22(9), 309-315.
Rosenblum G.D., & Lewis, M. (1999). The relations among body image, physical
attractiveness and body mass in adolescence. Child Development, 70, 50-64.
Page 16 of 17
Saenger P. (2003). Precocious puberty: McCune-Albright syndrome and beyond. Journal of
Pediatrics, 143(1), 9-10.
Styne D.M. (2002). The testes: disorders of sexual differentiation and puberty in the male. In
M.A. Sperling (Ed.), Pediatric endocrinology (pp. 565-628). Philadelphia: Saunders.
Warren M.P., & Fried J.L. (2001). Hypothalamic amenorrhea. The effects of environmental
stresses on the reproductive system: a central effect of the central nervous system.
Endocrinology and Metabolism Clinics of North America, 30(3), 611-629.
Warren M.P., & Vu C. (2003). Central causes of hypogonadism–functional and organic.
Endocrinology and Metabolism Clinics of North America, 32(3), 593-612.
Weinshenker N. (2002).Adolescence and body image. School Nurse News, 19(3), 12-16.
Williams J.K. (1995). Parenting a daughter with precocious puberty or Turner syndrome.
Journal of Pediatric Health Care, 9(3), 751-752.
Zacharias L., Rand W.M., & Wurtman R.J. (1976).A prospective study of sexual
development and growth in American girls: the statistics of menarche. Obstetrical and
Gynecological Survey, 31(4), 325-337.
Zosi P., Karakaidos D., Triantafyllidis G., Milioni N., Franglinos P., & Karis C. (2002).
Natural course of pubertal gynecomastia. Endocrine Abstracts, 4, P18.
Page 17 of 17