B6. Physiology of puberty and menarche

Puberty and menarche

Puberty is a period of transition from sexual immaturity to sexual maturity, during which both internal changes (to the gonads and adrenals) and external changes occur.

In females, puberty usually begins in the age of 8 – 12, while in males, it usually begins in the age of 9 – 13. However, the timing of pubertal onset varies wildly among countries and ethnicities. Pubertal onset occurs earlier now than 20 years ago.

Internal changes

The internal changes include gonadarche and adrenarche.

Gonadarche is the activation of the gonads by FSH and LH. It is initiated by an unknown trigger which causes an increase in the pulsatile secretion of GnRH from the hypothalamus. This stimulates pulsatile secretion of FSH and LH. FSH stimulates the growth of the ovarian follicles, while both LH and FSH stimulate the production of oestradiol by the ovaries.

The unknown trigger of pulsatile GnRH secretion may involve increased levels of neuropeptides kisspeptin, neurokinin B, as well as decreased levels of inhibitory signals like GABA.

Adrenarche is the increase in production of androgens by the adrenal cortex.

External changes

We consider the onset of puberty simultaneously as the first external changes are visible, most commonly breast development in females and testicular enlargement in males. The external changes of puberty follow a consistent order:

• Thelarche – onset of development of breasts
  • Due to oestrogen action
  • Normally the first manifestation of puberty
• Pubarche – onset of development of pubic hair, changed body odour, acne
  • Due to androgen action
  • May rarely occur before thelarche
• Menarche – onset of menstruation
  • Due to oestrogen action
  • Normally occurs 2 – 2,5 years after onset of puberty

The external changes can be tracked by the Tanner stages. There are five Tanner stages, where stage 1 is the prepubertal stage and stage 5 is the adult stage. In girls, these stages are based on the breast development and development of pubic hair. In boys, they’re based on the size of the testicles and development of pubic hair.

A growth spurt and change in body composition also occurs during puberty.

Precocious puberty

Precocious puberty is defined as onset of puberty earlier than what’s normal for the population. This depends on the population, but it’s generally defined as 2 – 2,5 standard deviations earlier than population norms. In Hungary and most similar countries, it’s defined as puberty before 8 years in females and 9 years in males.

Females are more often evaluated for precocious puberty than males. This could be due to biological differences or due to referral bias.

Precocious puberty is not necessarily pathologic, as it may be a normal variant. However, pathology must be excluded.

In case of a patient presenting with early development of secondary sexual characteristics, it’s important to answer these three questions:

1. Is this really precocious puberty? I.e., is this early enough as to fulfil the definition?
2. What is causing the precocious puberty?
3. Is therapy indicated?

Etiology

We can distinguish central and peripheral precocious puberty.

Central precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis.

• Idiopathic (most common)
• Brain tumour
• Brain trauma
• CNS infection

Peripheral precocious puberty is caused by excess peripheral secretion of sex hormones.

• Functioning ovarian cyst
• Ovarian tumour
• Congenital adrenal hyperplasia
• Hypothyroidism
• McCune-Albright syndrome

Clinical features

People with central precocious puberty usually have normal pattern and timing of pubertal events, except that it occurs early.

People with peripheral precocious puberty usually don’t have a normal pattern and timing of pubertal events. For example, they can experience menarche already one year after thelarche.

Diagnosis and evaluation

It’s important to differentiate central and peripheral. FSH and LH levels are the most important in this, as they’ll be high in central and low in peripheral.

A GnRH stimulation test may also be used. The FSH and LH levels after administration of an GnRH are measured. If they increase compared to baseline, it’s indicative of central. If there’s no increase, it’s indicative of peripheral.

X-ray of the hand can be used to determine the bone age.

Treatment

Treatment involves treating the underlying cause. For central type, GnRH agonists may be used to prevent premature fusion of growth plates if the patient’s bone age predicts that the growth plates will close before they reach a normal adult height.