Sexual Differentiation
and Development: II Puberty
Clinical background
Delayed puberty is one of the most
common referrals to paediatric and adult endocrine clinics. It is defined as
absence of breast development in a girl by 13.5 years or failure of testicular
growth to >4 ml by 14 years in a boy. Constitutional delay of puberty is by
far the most common diagnosis in boys, accounting for around 80% of cases,
whereas in girls delayed puberty is more likely to reflect serious underlying
pathology. Clinical assessment of boys with delayed puberty should be aimed
towards identifying patients with individual underlying pathology. If
constitutional delay is confirmed then treatment is conservative to observe
any spontaneous development over 6–8 months. If no pubertal change is evident
then treatment with low-dose testosterone will induce hypothalamic–pituitary
activity and trigger the onset of puberty. In girls with delayed puberty and
primary amenorrhoea a specific cause is more usually found. Clinical
examination will establish signs of Turner syndrome and subsequent
investigations must include karyotype analysis. Treatment is specific for the
underlying cause.
Puberty
Puberty describes a series of events
associated with a growth spurt and culminating in the acquisition of sexual
maturity and reproductive function. The phenotypic changes of puberty follow a
set pattern (Fig. 24a). Any deviation from the ‘consonance’ of puberty suggests
an underlying abnormality. The timing of puberty is influenced by genetic
factors and, critically, by body weight and composition. Over the last century,
in the Western world, the age of onset of puberty has become earlier, in
association with an increase in final height. In boys, puberty begins with the
attainment of testicular volumes of 4 ml but the growth spurt occurs late in
puberty and is predicted by a testicular volume of 10 ml. Conversely, in girls
growth is an early pubertal event occurring with the onset of breast
development.
Growth and puberty. Increases in gonadal steroid production at puberty
stimulate the production of growth hormone. GH is secreted in a pulsatile
fashion at night and there is an increase in the amplitude of GH pulses during
normal puberty, although not their frequency. Increased GH secretion is
reflected in the pubertal growth spurt which forms a crucial part of the
maturational processes during adolescence. Absence or delay in the growth spurt
usually indicates lack of consonance of puberty and requires investigation.
Adrenarche. Adrenal androgen secretion increases before
puberty, at about age 6–8 years, and is associated with the onset of the
development of axillary and pubic hair and apocrine sweat glands and, usually,
a small increase in height velocity.
Endocrine regulation of puberty
The hypothalamic–pituitary–gonadal
axis is active in fetal life with high gonadotrophin concentrations seen in the
first half of gestation followed by reduced levels in the second half, thought to
be due to a developing negative feedback system by gonadal steroids. In the
immediate postnatal period gonadotrophin levels are high, related to the
withdrawal of placental steroids and alterations to the negative feedback
equilibrium. Gonadotrophin levels subsequently fall and remain low throughout
early childhood, although detectable LH pulses can be identified as early as 6
years.
The onset of puberty is marked by a
rise in LH secretion, which occurs firstly as nocturnal pulses. This occurs
several years before the onset of phenotypic puberty and is in response to
increased GnRH secretion and enhanced responsiveness of the pituitary
gonadotrophs to the GnRH stimulus. Evidence for pulsatile LH secretion can be
seen in ovarian ultrasound scans of normal prepubertal girls which show
multiple ovarian follicles distributed throughout the ovary, an appearance
typical of pulsatile LH input (Fig. 24b).
The factors that regulate the onset of
LH secretion at the start of puberty remain to be fully elucidated but a number
of neu- rotransmitters and other endocrine, paracrine and autocrine factors
have been identified that modify the hypothalamic–pituitary–gonadal axis at
this time. It has been recognized for some time that body weight and body
composition affect the onset of puberty and the hormone leptin, derived from
peripheral adipose tissue, plays a major role in signalling changes in body
composition to the hypothalamus.
LH secretion gradually increases with
the establishment of regular LH pulses occurring every 90 minutes during both
night and day. LH secretion results in the production of gonadal steroids and
the onset of secondary sexual characteristics. Increasing gonadal steroid
concentrations regulate the GnRH pulse generator, establishing the mature
diurnal variation and feedback systems seen in both sexes. In girls, estrogen
levels rise dramatically in the year before menarche, establishing the positive
feedback needed to induce a preovulatory LH surge. In boys, the regular LH
pulses result in peak testosterone concentrations in the early mornings (Fig.
24c).
Gonadal development in childhood
and puberty
In males, there is a rise in
testosterone production between the ages of 2 and 4 months associated with
Leydig cell multiplica- tion but after that the testes remain relatively
inactive until the onset of puberty. Testicular size increases from around the
age of 10 years, reflecting increased gonadotrophin secretion and growth of
seminiferous tubules.
In females, the elevated gonadotrophin
levels seen after birth decline by the age of 2–3 years and remain low
throughout childhood. The rise in gonadotrophin secretion seen by the age of 6
is associated with the development of antral follicles in the ovary and a rise
in estrogen concentration. The commencement of sex hormone production and
release during puberty is accompanied by gonadal and accessory sex organ growth
and function. The end of puberty is marked by the menarche with the onset of
regular ovulatory cycles.
