Puberty Notes

Puberty

Puberty is the age when males and females start developing secondary sexual characteristics.

Hormonal Changes

Hormonal changes during puberty are due to the activation of the hypothalamic-pituitary-ovarian axis. These changes are influenced by neurotransmitters.

Neurotransmitters

Increased Neurotransmitters (LPG)

  • Leptin (L): Plays a permissive role in puberty.
  • Kisspeptin (P): Responsible for the pulsatile release of GnRH.
  • Glutamate (G)

Decreased Neurotransmitters

  • GABA: Keeps the hypothalamus dormant before puberty.
  • Neuropeptide Y

GnRH Release

Changes in neurotransmitters cause the arcuate nucleus of the hypothalamus to release Gonadotropin-Releasing Hormone (GnRH) in a pulsatile manner.

  • Initially, GnRH is released only at night, leading to Luteinizing Hormone (LH) release.
  • Later, both LH and Follicle-Stimulating Hormone (FSH) are released during the day and night.

LH and FSH Action

LH and FSH act on the ovaries, leading to the release of estrogen and progesterone.

  • Estrogen is primarily responsible for the development of secondary sexual characteristics.
  • Estrogen has a negative feedback effect on FSH, and progesterone has a negative feedback effect on LH.

Key Questions About Neurotransmitters

  • Which neurotransmitter keeps the hypothalamus dormant before puberty? GABA
  • Which neurotransmitter is responsible for the pulsatile release of GnRH? Kisspeptin
  • Which neurotransmitter acts as a somatic stimulus for the onset of puberty (permissive role)? Leptin

Age of Puberty

  • Normal females: 10 years
  • Males: 11 years

Pubertal events occur approximately one year later in males compared to females.

Sequence of Pubertal Events in Females

  1. Growth spurt: Initiation of skeletal growth (first sign).
  2. Thelarche: Appearance of breast budding (first visible and most specific sign).
  3. Pubarche: Appearance of pubic and axillary hair.
  4. Peak height velocity: Attainment of peak height.
  5. Menarche: Onset of menstruation (approximately two years after the onset of puberty, typically at age 12). Chromosomes 6 and 9 are involved in menarche

Sequence of Pubertal Events in Males

  1. Testicular enlargement (first sign).
  2. Penile enlargement.
  3. Pubarche: Appearance of axillary and pubic hair.
  4. Peak height velocity.

Secondary Sexual Characteristics in Females

Breast development is the most important secondary sexual characteristic.

  • Estrogen is the primary hormone responsible for most pubertal events, except for the appearance of pubic and axillary hair (which is influenced by androgens).
  • Breast and pubic hair development occurs in stages, as defined by Tanner staging.

Tanner Stages

Tanner described 5 stages for breast and pubic hair development:

  • Stages 1 and 2: Initial stages of development (less developed).
  • Stages 4 and 5: Fully developed breast and pubic hair.

Early Onset of Puberty (Precocious Puberty)

  • Females: Breast budding before 8 years of age.
  • Males: Testicular enlargement before 9 years of age.
  • Precocious menstruation: Onset of menarche before 10 years of age.

Causes of Precocious Puberty

  • Most common cause: Idiopathic.
  • More common in girls.

Treatment involves decreasing estrogen levels by administering GnRH in a continuous manner.

Delayed Puberty

  • Females: No secondary sexual characteristics by 13 years of age.
  • Males: No testicular enlargement by 14 years of age.

Causes of Delayed Puberty

  • Most common cause: Constitutional delay.
  • More common in boys

Treatment involves stimulating the hypothalamic-pituitary-ovarian axis by administering GnRH in a pulsatile manner.

Central vs. Peripheral Precocious Puberty

Central (True) Precocious Puberty

Premature activation of the hypothalamic-pituitary-ovarian axis.

  • Increased LH, FSH, and estrogen levels.

Peripheral Precocious Puberty

Peripheral production of estrogen or androgen, not due to activation of the hypothalamic-pituitary-ovarian axis.

  • Decreased LH and FSH levels (due to negative feedback from increased estrogen).
  • Increased estrogen levels.
  • Can be isosexual or heterosexual
FeatureCentral Precocious PubertyPeripheral Precocious Puberty
Hypothalamic-Pituitary AxisPremature ActivationNot Activated
LH and FSH LevelsIncreasedDecreased (due to negative feedback)
Estrogen LevelsIncreasedIncreased
Isosexual/HeterosexualIsosexual (consistent with genetic sex)Can be isosexual or heterosexual. Heterosexual precocious puberty can occur due to an increase in androgens, leading to the development of male secondary sexual characteristics in females (e.g., hirsutism, deepening of voice, increased muscle mass)

Causes of Central Precocious Puberty

  • 90% cases are idiopathic.
  • 10% cases are due to brain tumors (e.g., hamartoma of the tuber cinereum).
  • MRI of the brain should be performed to rule out brain tumors.

Causes of Peripheral Precocious Puberty

  • Increased estrogen:
    • Estrogen-producing ovarian tumors (e.g., granulosa cell tumor).
    • Hypothyroidism (due to the similarity between TSH and LH/FSH alpha subunits). TSH, LH, FSH share the same alpha subunit.
    • McCune-Albright syndrome (cafe au lait spots, polyostotic fibrous dysplasia, precocious puberty).
  • Increased androgens:
    • Sertoli-Leydig cell tumor (androgen-secreting tumor of the ovary).
    • Congenital adrenal hyperplasia.

Treatment

  • Central precocious puberty: GnRH agonists (continuous administration).
  • Peripheral precocious puberty: Treat the underlying cause.

Practice Questions

  1. Which pubertal event is NOT estrogen-dependent? Growth of hair.
  2. A nine-year-old girl with breast and pubic hair development shows increased LH pulses during sleep. This is characteristic of central precocious puberty.