PUBERTY

Definition
 A phase of development between childhood and complete, functional maturation of the reproductive
glands and external genitalia

Phases of pubertal changes

 Adrenarche: activation of adrenal androgen production
 Gonadarche: activation of reproductive glands by the pituitary hormones FSH and LH
 Thelarche: onset of breast development
 Pubarche: onset of pubic hair growth
 Menarche: onset of menstrual bleeding
o Anovulatory cycle: The menstrual cycle may be irregular in adolescents during the first few
months/years after menarche.
 Immaturity of the hypothalamic-pituitary-gonadal axis; irregular menses and heavy
menstrual bleeding

Physiology
 Unknown initial trigger → ↑ activators and/or ↓ inhibitors of GnRH secretion
→ pulsatile GnRH secretion→ ↑ FSH and ↑ LH secreted by the anterior pituitary gland → stimulation of
the Leydig cells and Sertoli cells in the testicles, and the theca and granulosa cells in the ovary.

Influential factors
 General health (nutritional state, bodyweight)
 Genetics
 Social environment

Girls
 Normal age of onset: 8–13 years
 Normal order of changes: adrenarche → gonadarche → thelarche (age of onset 8–11 years) → growth
spurt (age of onset 11.5–16.5 years) → pubarche (mean age of onset 12 years) → menarche (age of
onset 10–16 years, mean age: 13 years)

Boys
 Normal age of onset: 9–14 years
 Normal order of changes: adrenarche → gonadarche (age of onset 9–14 years) → pubarche (mean age
of onset 13.5 years)→ growth spurt (mean age of onset 13.5 years)→ androgenic hair growth
The first visible sign of puberty in males is testicular enlargement, while in females it is breast development.

Physical changes during puberty

Tanner stages
 A sexual maturity rating (SMR) scale used to assess the development of secondary sexual characteristics

Tanner Stages Breast development (girls)

Prepubertal appearance and size

B1
Occasional elevation of the nipple

Enlarged mammary glands form a breast bud

B2
Slight increase in areolar diameter, nipple protrusion

B3
Further enlargement of mammary glands
Breast bud extends beyond the areolar diameter

B4 Nipple and areola form a secondary mound which projects above the breast tissue

Adult breast
B5
Areola with projection of papilla only

Genital development (boys)

G1 Prepubertal appearance and size of the testes, scrotum, and penis

Testicular volume of 4 mL

Larger scrotum
G2 Penile growth has not begun
Scrotal skin darkens in color and texture

Continued enlargement of the testes and scrotum

G3
Penile growth begins

Testicular volume of 12 mL

Scrotum growth
G4
Penile growth continues: longer and wider penis
Development of penis glans

G5 Testes, scrotum, and penis attain adult appearance and proportions

Pubic hair development (boys and girls)

Ph1 Usually no pubic hair, vellus hair possible

Ph2 Sparse, lightly pigmented hair (straight or curled) on the labia/base of the penis

Ph3 Dark, coarse, curly hair spreading over the pubic symphysis

Ph4 Adult pubic hair that does not extend to the inner thighs

Ph5 Adult pubic hair that extends to the inner thighs with horizontal upper border

Ph6 Further growth of pubic hair along linea alba in the direction of the umbilicus

Other morphological changes during puberty  [3][4][5]

 Growth spurt
 o generally occurs between ages 13–15 years (in girls, it can begin two years earlier).
o Includes ↑ growth in trunk and limbs
o Assessed using growth velocity charts
 Bodyweight and composition during adolescence
o Boys: initial ↓ body fat (early puberty) → ↑ lean body mass (late puberty)
o Girls: gradual increase in body fat
 Dermatological changes  [6]

o Acne vulgaris
o Activation of the adrenal cortex → pubertal hormonal fluctuation → ↑ sebum secretion and
excessive sweating → skin and hair changes
 Other physical changes associated with menarche: anemia

Stages of adolescence
Adolescence is the period of physical, cognitive, and psychosocial development from the onset of puberty to adulthood

Stage
Onset Features
of adolescence  [7][8]

Start of growth spurt and genital development

Self-esteem and body image issues
10–14 Development of sexual orientation
Early
years Mood swings
Limited abstract thinking
Peer identification

Physical growth continues for males, but slows down for females
Menarche, spermarche
15–16 Development of an independent identity
Middle
years Increased drive to become independent
Interested in moral reasoning
Increased health risk (e.g., smoking, drugs, alcohol)

End of puberty changes

Further development of identity
Late ≥ 17 years Development closer relationships with individuals
Rational thinking
Awareness of the future

 Associated with an increased risk of morbidity and mortality due to an increase in risk-taking behavior.

o sexually transmitted infections, eating disorders, depression
o motor vehicle accidents, suicide, and homicide

Precocious puberty

Definition  [9]

 The appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys

Classification
 Central precocious puberty (gonadotropin-dependent precocious puberty, true precocious puberty)
 Peripheral precocious puberty
 Heterosexual precocious puberty: masculinization of girls or feminization of boys
o Boys: See “McCune-Albright syndrome” and “Leydig cell tumors.”
o Girls: See “Congenital adrenal hyperplasia.”
 Benign pubertal variants
o Precocious thelarche
o Idiopathic premature pubarche
o Premature adrenarche
o Precocious menarche
 Obesity-related precocious sexual development

Central precocious puberty  [3][9][11]

Definition
 Precocious puberty with elevated GnRH levels

Etiology
 Idiopathic (most common cause)
 CNS lesions
 Obesity-related precocious sexual development

Pathophysiology
 Early activation of the hypothalamo-hypophyseal axis → abnormally early initiation of pubertal changes → early
development of secondary sexual characteristics

Clinical features
 Premature sexual development typically follows the normal pattern of puberty
 Symmetric development of secondary sexual characteristics or, occasionally, as
isolated premature thelarche, adrenarche, or menarche.
 Increased growth velocity: Children tend to be taller than their peers during adolescence, but are of shorter
stature by the time they reach adulthood (due to early closure of the epiphyseal plate).

Diagnosis
 Laboratory tests
o Serum LH and FSH: increased
o GnRH stimulation test (gold standard): evaluates the reactivity of the hypothalamic-pituitary-axis
to GnRH stimulation
 Gonadotropin (LH and FSH) levels increase after intravenous administration of GnRH.
o Serum testosterone/estradiol: increased
 Imaging
o X-ray of the left hand and wrist: allows comparison between skeletal maturation and chronological age
 Bone age is within 1 year of a child's age: Puberty likely has not started
 o MRI/CT of the brain with contrast: when ↑ LH is confirmed

Treatment
 GnRH agonist (e.g., leuprolide, buserelin, goserelin): to prevent premature fusion of growth plates

Peripheral precocious puberty  [3][9][11][12]

Definition
 Precocious puberty without elevated GnRH levels (due to ↑ peripheral synthesis of or exogenous exposure to
sex hormones)

Etiology
 ↑ Androgen production
o Congenital adrenal hyperplasia
o Virilizing ovarian and adrenocortical tumors (e.g., Sertoli-Leydig cell tumor, Leydig-cell tumor)
 ↑ Estrogen production
o McCune-Albright syndrome
o HCG-secreting germ cell tumors (e.g., dysgerminomas)
 Primary hypothyroidism
 Exogenous steroid use
 Obesity-related precocious sexual development

Clinical features
 May not follow the normal developmental pattern (signs of estrogen or androgen excess)
 May exhibit possible features of an underlying condition

Diagnosis
 Laboratory tests
o Serum basal FSH and LH: decreased
o GnRH stimulation test
 No increase in LH levels after GnRH administration
 Precocious pseudopuberty is associated with low basal LH levels (prepubertal values).
o Serum testosterone/estradiol levels: increased (depending on the tumor)
o TSH, T  hormone: suspicion of hypothyroidism
3

 Imaging
o X-ray of left wrist and hand: accelerated bone growth

Delayed onset of puberty

Definition  [22][23][24]

 Absent or incomplete development of secondary sex characteristics by the age of 14 years in boys or 13 years in
girls

Etiology  [24][25]
 Physiological causes: constitutional growth delay
 Pathologic causes
o Hypergonadotropic hypogonadism
o Hypogonadotropic hypogonadism
o Malnutrition
o Chronic diseases

Clinical features
 Clinical features: depend on the underlying condition
 Physical examination
o Tanner staging
o Assessment of height

Diagnosis  [24][25]

 Medical history
 Routine tests
o Serum LH, FSH, and testosterone/estradiol
 Low or normal with low testosterone/estradiol: constitutional growth delay
 Elevated: primary hypogonadism
o X-ray of the left hand and wrist
 delayed bone age (less than the individual's chronological age)
 Additional tests: based on suspected etiology

Treatment  [25]

 Constitutional growth delay: expectant management

o the individual reaches a normal adult height
 Other pathologies
o Treatment of the underlying disease
o Hormonal therapy
 Testosterone: used in boys to achieve secondary sex characteristics (e.g., virilization, growth spurt)