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7.3 Clinical Rounds

1. What is delayed puberty?

Delayed puberty is defined as lack of development of secondary sexual charac-

teristics at an age corresponding with the established normal standards for chil-

dren of the same gender and race. In clinical practice, absence of testicular

enlargement by the age of 14 years in boys or lack of breast development by

13 years in girls is used to define delayed puberty. In addition, children with

normal age of onset of puberty, but without progression of pubertal events over

a period of 2 years (arrested puberty), or those with significant delay in the

progression of pubertal events (>5 years between thelarche and menarche in

girls or >5 years between onset of testicular enlargement and complete genital

development in boys) are also considered to have delayed puberty.

2. How were the age cutoffs for delayed puberty defined?

The age of onset of puberty in a population is normally distributed (bell- shaped

curve with a Gaussian distribution). In the studies by Tanner and Marshall, it

was shown that the mean age of onset of puberty was 10.5 years in girls and

11.5 years in boys, with one standard deviation of approximately 1 year.

Considering the normal range of age of pubertal onset as mean ±2.5 SD, lack of

any sign of pubertal development after the age of 13 years in girls or after

14 years in boys (+2.5 SD from the mean, i.e., 10.5 + 2.5 years in girls and

11.5 + 2.5 years in boys) suggests delayed puberty.

3. Why is pubarche not used to define the onset of normal puberty?

Reactivation of hypothalamic–pituitary–gonadal (HPG) axis is manifested by

thelarche in girls and testicular enlargement in boys, and these are considered as

first signs of puberty. Pubarche is a clinical manifestation of adrenarche and

denotes the maturation of zona reticularis which is independent of reactivation of

HPG-axis. Therefore, pubarche is not used to define the onset of normal puberty.

4. What is kisspeptin?

Kisspeptin is a neuropeptide secreted from the arcuate nucleus and anteroven-

tral and periventricular (AVPV) nuclei of the hypothalamus. The arcuate

nucleus comprises of KNDy (pronounced as “candy”) neurons which co-

secrete kisspeptin (K), neurokinin B (N), and dynorphin (Dy), whereas AVPV

nuclei comprise of Kiss-1 neurons, which secretes only kisspeptin. Both KNDy

neurons and Kiss-1 neurons synapse with GnRH neurons. Kisspeptin acts on its

7 Delayed Puberty