Puberty in females and males

A number of terms is used to defined puberty and

their stages

Describe the major hormones at birth and

how do they change over puberty
All sex hormones are present from birth but at
very low levels.
GnRH comes from the hypothalamis
Pituitary LH and FSH are identical in both male
and female
- Testosterone and oestradiol are the
steroid hormones which increase 20-30 fold
over puberty
- Testosterone = DHT in periphery
- Oestradiol derived from testosterone
Progesterone from ovary matures breast
development
Increase in growth hormone production by
anterior pituitary
- increase in IGF1 from liver and in tissues
Describe the initiation of puberty
-

Increased frequency and amplitude of

GnRH pulses from neurons in
hypothalamus
GnRH stimulates release of pituitary
gondotrophics
Initially its an nocturnal event so
testosterone and oestrogen raised in
morning only in EARLY puberty

Leptin production from adipose tissue has a

permissiverole = measure of energy store
NEEDED for physical growth
What happens in FEMALE puberty?
1. Increased frequency and size of FSH pulses
= ovarian follicles produce increasing
amounts of oestradiol
2. Increased frequency and size of LH pulses
a. Ovarian thecal cells (stromal)
growth = progesterone and
testosterone
Physical changes
- Cervix, uterine muscle and uterine lining
(endometrium) growth under influence of
oestradiol
- Fluctuation in oestradiol = withdrawal
bleed (shedding of endometrium)
Menarche
- HIGH oestradiol = positive feedback on LH
with pre-ovulatory surge
Describe the trend of Mecharche
Mean age in Australia is 12.3
- There has been a falling of this page in
westernised countries
- Percentage of body fat required to achieve
menarche (in evoluntionary terms required
for pregnancy and breast feeding)
What puberty changes happen in males?
Increased frequency and size of LH pulses
stimulate LEYDIG cells testoerone increases
Increases frequency and size of FSH pulses
SEMINIFEROUS TUBULE and SERTOLI cells
increase testicular size
- There is a secular trend for earlier onset of
testicular enlargement over last 30 years
Seminal vesicule and prostate enlargement
Penile growth
Sperm production from about 13.5 years

What factors influence GnRH production?

Kisspeptin1
- Neurons in arcuate nucleus
- Endogenous ligand of the GPR54 receptor
which is a G protein receptor
- The kisspeptin 1 receptor on the GnRHproducing-neuron
Thus if the signalling is absent = no puberty
Other
-

peptides from the arcuate nucleus

neurokini B (TAC 3) = accerelator
Dynorphin pubertal brake
Makorin RING-finger 3 gene (MKRN3)
product is a brake

What are the onset and duration of puberty?

Tanner pubic hair

Describe the height growth in females and

males
Females
- 8-9 cm in a year
- Early puberty there is a growth spurt and is
initiated and maintained by
o Ovarian oestradiol at low levels
o AND pituitary growth hormone/IGF1
- 20 cm average gain
- Stopped by epiphyseal closure when there
is high levels of oestradiol
Males
- 9-11/5cm/year
- Growth spurt is a LATE puberty event
o HIGH levels of testicular
testosterone
o AND pituitary growth hormone IGF1
- 30cm average age
- Halted by closure of epiphyseal from
oestradiol (which is aromatisation from
testosterone)
Describe the body composition change in
puberty

Since there is lots of variety in puberty

there are various tools.
Tanner breast stage

Tanner genital stages male

How is bone /osseous age determined?

Used to as a descriptor of developmental age
X ray of hand and wrist
- Tanner whitehouse
- Greulich Pile
These are TWO grading system which the
individual Xray is compared with radiographic
pictures
What are secondary sexual characteristics
What do the numbers mean?
1. Female growth spurt Breast 2/3 (based on
the bone age from those two systems)
2. Mecharce Breast
a. 95% of heigh complete
b. bone age is around 13.5 years
3. Male growth support Genital
4. Voice break
a. Vocal cord length, larynx and
cricothyroid cartilage increases
b. Laryngeal muscles enlarge
5. Body and facial hair
a. Dependent on sensitivity of
androgen receptor
6. Acne
a. Result of increasing testosterone
What are the factors that increase bone
mass
GH/IFG1, oestradiol OR testosterone, dietary
calcium nd Vitamin D, physical activity
What are the end points of puberty?

Due to the change in balance between

Testosterone and oestrogen
Generally requires no treatment (but may required
surgical removal or aromatase inhibitors)
IF prolonged consider secondary causes
- drugs
- Thyrotoxicosis
- Klinefelter syndrome 47XXY
- Feminising tumours (rare)
What is Adrenarche?
-

Maturation of adrenal zona reticularis

o Independent of gonadal puberty
and biochemically starts before
gonal maturation
o Clinically detected as pubic hair,
seborrhoea of hair and skin and
increased body odor
o ACTH trigger (possibly)

What factors will vary the timing of the

ONSET of puberty
Endogenous
1. Genetics
2. Birth circumstances (earlier puberty)
3. Obesity (earlier in girls)
4. Malnutrition or excessive exercise
(delayed)
5. Chronic illness (delayed)
6. Visual impairment (earlier)
7. Overseas adoptee (earlier)
Exogenous
1. Chemical pollutants (which are endocrine
disruptors)
a. Delayed or advancement of puberty
b. Earlier breast development in
females
c. Hypospadia and lower sperm count
in developed countries
2. Westernised environment = earlier
a. Change in nutrition and physical
activity
b. Changes in body composition
c. Reduced childhood infections
3. Absent biological fathers = earlier in girls
What age is still considered NORMAL range
for puberty in females and males
- 8/13 years in females
- 9 /14in males
More common in females to be EARLY and easier
to detect
Based on early rises in Testosterona and oestrodiol
Delay difficult to differentiate extreme delay
from absent puberty
- BONE age is always delayed
What is gynaecomastia?
Male breast occurring in over 80% of males in
tanner stage G3/4

What is hirsutism
- Increase in terminal hair due to increased
androgen sensitivity
- Exclude endocrine disorders if menstrual
disturbances and acne
o Polycystic ovaries
o Adrenal gland disorders
These are generally benign but may need
endocrine assessment as they may indicate
abnormal early puberty
Premature adrenarche
- Present earlier than expected with
o Secondary sexual hair
o Acne and seborrhea
o Increased body odour
- Low birth weigth children has increased
frequency
- Some advancement of bone age
- Mild increase in plasma adrenal androgens
Important to exclude adrenal or gonadal
pathology
Treatment
- Females may present later with polycycstic
ovaries
Premature thelarche
- Breast development BEFORE 8 with NO
other pubertal signs
- Diagnosis = must have prepubertal
oestradiol levels
Important to exclude
- Ecogenous oestrogen source
- True precocious puberty with advanced
bone age and elevated oestradiol
Treatment = none, may regress
OTHER pathological variations in puberty
that require evaluation
- Vaginal bleeding but absent or early breast
development
- Small testicles, young age and penile
enlargement
What conditions can cause absent puberty
and what can cause early puberty

Absent puberty due to primary gonadal

failure
- High FSH and LH and low oestradiol
o Sex chromosome abnormality with
gonadal damage
o Premature menopause
autoimmune
o Chemotherapy
o Galactosaemia
o Torsion
o Surgical removal
o Irradiation
- Treatment = hormone replacement therapy
required to initiate and maintain puberty

Causes
- Genetic pituitary deficiency
- Tumour replacing normal pituitary tissue
- Trauma = pituitary stalk especially
- Surgery often to remove tumour

Turner syndrome 45 XO and variation

Hypothalamus problem
Low FSH, LH and low oestradiol in females and low
testosterone in males (HENCE it is
indistinguishable on blood test from secondary
gonadal failure. GnRH is NOT measurable in
peripheral blood

What are causes of primary gonadal failure

in males?
High FSH and LH with low testosterone
Causes
- sex chromosome disorders
- chemotherapy
- Trauma and torsion bilaterally
- Crytorchidsm (undescending testicles)
- Radiation damage
- Infection (mumps)
Hormone replacement therapy oral testosterone
then parenteral preparations later
Klinefelter syndrome 47 XXY

What is secondary gonadal failure?

Pituitary failure
- Low FSH and LH with low oestradiol in
females or testosterone in males

Often associated with other hormone deficiencies

Treatment
- Use of oestradiol and testosterone as LH
and FSH can be only given injection as
peptides with a short half life
What is tertiary gonadal failure?

Causes
- Isolated GnRH deficiency or Kallman
syndrome (has anosmia)
- Head trauma
- Iron deposition Iron overload in
thalassemia major
- Tumour
- Raddiation or sugery therapy for tumour
- CHARGE syndrome, Prader Williw syndrome
Again, OFTEN associated with other hormone
deficiencies
GnRH is available as injection and is used in
female infertility
What is primary amenorrhoea?
Absent menarche from 16 years onwards
- Imperforated hymen
- Hypothalamic, pituitary or ovary
disorder
- Mullerian agensis 46XX = normal breast
development with absent uterus, fallopian
tubes and upper 2/3 vagina
- Complete androgen insensitivity
syndrome
o Receptor abnormality, XY
karyotype, femininsed with
endogenous oestradiol from
testosterone
o 46 XY
o Tall stature, female phenotype with
little body hair, inguinal gonads,
lower 1/3 vagina only (upper
structures regress with mullerian
inhibitory factor)
What is precocious puberty?
Puberty occurring TOO early
CCP = central precocious puberty

LH, FSH and oestradiol/testosterone follow

a NORMAL puberty pattern but it is TOO
early
80% is idiopathic in females but 20% in
males
MRI pituitary hypothalamic area

What is considered True CCP that is GnRH

dependent?
Females that present with breast development
with or without vaginal bleeding
Males that present with
- testicular enlargement
- penile enlargement
- voice change
- acne
Treatment is with GnRH agonist
- Continuously as depot injection and to
down regulate pituitary GnRH receptor
- GnRH agonists improve final height and
reduce psychosocial distress
There is also GnRH independent pseudoprecocious puberty
Isosexual (same sex puberty change) form
- Low gondaotrophins but elevated
Oestradiol or testosterone
1. McCune-Albright syndrome in females
a. Instrinsic hyper function of ovarian
FSH receptor
2. Testotoxicosis in males
a. Intrinsic hyperfunction fo testicular
LH receptor
3. Ovarian/testicular tumours
4. Adrenal tumours
5. Exogenous oestrogen/androgens
Contrasexual opposite sex puberty change
Low gondaotrphincs with high oestradiol IN MEN
or HIGH testosterone in FEMALE (opposite)
-

Females: virilisation, acne, deep voice, loss

of body fat, clitoromegaly
o Congenital adrenal hyperplasia
o Adrenal or ovrian tumour
o Exogenous androgen exposure
Male feminisation, breast development,
muscle loss
o Adrenal or ovarian tumour
o Exogenous oestrogen exposure

Therapy in adolescence
Complaince = health care professional driven
Adherence therapeutic alliance
Capacitance ability of the patient
Concordance implies both patient and helath
professional negotiate, understood and agreed
upon a medical course of action
Measurement of therapy adherence
- Patient spontaneously owns up
- Rate their adherence out of 10
- Loss of disease control or failure to respond
to empirically supported interventions
- Poor clinic attendance record
- Questionnaire
Rate of prescription refill
Pill count
Plasma or urine for drug substance levels

Adolescents are different

- Family to remind them
- Need to be normal
- Running out of medication and cost
impoverish families
- When adverse effects are not immediate
e.g. hypertension
- No imrpovements = failure to understand
- Adverse effects
Adverse effects in children can be
- Real or imagined
- Extremely averse to medications that alter
body image and tend to be impulsive and
can cease all medication
- See little difference between digital and
person to person communication and thus
overly influenced by media
The internet and medical information
Adolescents search for general medical conditions,
body image and nutrition and sexual health
- Large amounts of unsolicited information
Theory of planned behaviour
Hleath professionals focus on
- Behavioural belief link action to outcome
- Attitude toward the behaviour might be
reflect behavioural belief

Reasons for poor compliances

Patients decision making is

- Normative belief = person perceives
important persons in their life think they
should do
- Subjective norm social pressure
- Control belief personal beleifs about
mastery)
- Perceived behavioural control how
effective a person think they will be
Puberty can have an impact on illness
control due to
- Change in body size and thus dosage is
sub-optimal when using body weight
- Increase in growth hormone temporary
increase in insulin resistance and higher
insulin doses required
- Lung volume more rapid gender specific
deteration in females

Glomerular mass unable to accommodate

growth in CKD
Conversion of hydrocortisone to cortisoine
(inactive) from oestradiol increase
Mensraul cycle can affect control of chronic
illness
o Epilepsy
o Migraine
o T1DM

Normal adolescent development problems

1. Normal brain development
2. Autonomy
3. Priorities
4. Life is about present
Non adherenace implications on therapy