PUBERTY

Puberty is the stage of physical maturation in which an

individual becomes physiologically capable of sexual
reproduction.
It is associated with growth spurt and appearance of both
primary and secondary sexual characteristics in children.
It occurs between 8 and 14yrs in girls and between 9 and
14yrs in boys.
The age at which puberty begins is related to the amount of
body fat and level of physical activity of the child.

Influencing Factors:

Genetics: 50-80% of variation in pubertal timing (as race)

Environmental factors e.g. nutritional status (obese are more

likely to be earlier)

Excessive exercise

Psychological factors.
 Normal Puberty: Endocrine control:
•Before birth

•Newborn

•Until 3 months of age > decline

•Childhood
Suppression “CNS inhibition of hypothalamus “
“ feedback of low estradiol due to high sensetivity ”
Leptin → regulates appetite and metabolism through
hypothalmus. Permissive role in regulation of timing of puberty
Prior to puberty:

The hormonal feedback / central neural suppression of

GnRH release suppresses the onset of puberty.

In the foetus,
the Hypothalamo-pituitary-gonadal axis starts working, and
after birth,

Sex hormones and gonadotrophins (FSH, LH) are found in

adult levels

Levels reduce in months after birth; pulsatile GnRH reduces

in childhood and increases in frequency and amplitude before
puberty

The onset of puberty is signalled by the secretion of pulses of

Gonadotrophin Releasing Hormone (GnRHS

For 2 yrs before puberty, rise in adrenal androgens early

pubic hair and spots
Physiology of puberty
Activation of the hypothalamic – pituitary – gonadal axis
induces and enhances progressive ovarian and testicular sex
hormone secretion and is responsible for the profound
biological, morphological and psychological changes which
adolescents experience.

In the later pubertal period, i.e between age 8-11, the Adrenal
cortex secretes

DHEA, DHWA-S and Androstenedione .

These Androgens results in Adrenarche (Pubarche )

↑ GnrH > promote ovarian follicle maturation and sex
steroid production .

Resulting in development of Secondary sexual features

 Physical changes:
5 stages are recognised from childhood to full maturity i.e. the
Marshall and Tanner (P1 – P5)

It reflects the progression in changes of the external genitalia

and of sexual hair and secondary sexual characteristics

Mean age

10.5yrs in girls and

Mean age in boys is 11.5 – 12yrs

Puberty in girls

•Thelarche (Breast budging) is usually first sign and is often

unilateral.

•Menarche is usually 2-3 yrs after breast development

•Growth spurt peaks before menarche.

•Pubarche (Pubic and axillary hair growth): sign of adrenal

androgen secretion

•Starts at similar stage of apocrine gland sweat production and

associated with adult body odour
Pubertal stages in females (Tanner)
•P1 Prepubertal

•P2 Early development of subareolar breast bud +/- small

amounts of pubic and axillary hair

•P3 Increase in size of palpable breast tissue and areolae,

increased dark curled pubic/axillary hair

•P4 Breast tissue and areolae protrude above breast

level. Adult pubic hair but no spread to medial thighs.

•P5 Mature adult breast. Pubic hair extends to upper

thigh
Menarche:

Mean age in USA is 12.4 years

•During puberty, oestradiol levels fluctuates widely (reflecting

successive waves of follicular development that fail to reach
ovulatory stage)

•Endometrium is affected by oestradiol and undergoes cycles

of proliferation and regression until a point where withdrawal
of oestrogen results in the first menstrual bleed (menarche)
Ovarian development

Rising levels of plasma gonadotrophins stimulates ovary to produce

increasing amounts of oestradiol.

Increase Oestradiol leads to the development of secondary sex

characteristics.

Breast growth and development

Reproductive organ growth and development

Fat redistribution (hips,breasts)

Bone Maturation
In pre-puberty,

the ovarian size and volume extends from 0.3 to 0.9cm3.

More than 1.0 cm3 indicates that puberty has begun.

During puberty, the ovarian size increases rapidly to a mean post-

pubertal volume of 4.0 cm3 (1.8 to5.3cm3)
Ovulation

Plasma testosterone levels also increase at puberty although not as

markedly as in males.

Plasma progesterone remains at low levels even if secondary sexual

characteristics have appeared.

A rise in progesterone after menarche is, in general, indicative that

ovulation has occured.

The first ovulation does not take place until 6-9 months after
menarche because the positive feedback mechanism of estrogen is
not developed.
Development of the uterus

•Neck and isthmus account for up to 66% of uterine volume

•Pre-pubertal uterus is tear-drop shaped

•Following production of oestrogens – uterus becomes pear

shaped

•Uterine body increases in length (max 5 – 8cm) and thickness

(proportionately more than cervix)
PUBERTAL STAGES (TANNER) MALE

P1 Prepubertal, testicular length less than 2.5cm

P2 Early increase in testicular size, scrotum slightly

pigmented, few long and dark pubic hair

P3 Testicular length 3.3-4 cm, lenghtening of the penis,

increase in pubic hair

P4 Testicular length 4.1-4.5cm, increase in length and

thickening of the penis, adult amount of pubic hair

P5 Testicular length greater than 4.5cm, full

spermatogenesis
Secondary sexual development in boys:

•growth kinetics are enhanced from early puberty on

•maximal velocity is attained only around 14 to 15 years of

age

•testis increases in size, mainly at the expense of the

seminiferous tubules

•the interstitial (Leydig) cells develop and ensure synthesis

and secretion of testosterone
a testicular volume of 4 ml or a longitudinal diameter greater
than or equal to 2.5 cm and

a slight progressive increase in scrotal folds and pigmentation

constitute the first signs of puberty

The increase in testicular size observed during pre-puberty and

puberty results essentially from the development of the
seminiferous tubules under the stimulating effect of FSH.

The testicular volume increases throughout puberty up to

Tanner stage P4 when a longitudinal diameter of 5.0 + 0.5 cm or a
volume of 17.6 + 4.0 ml is reached.
Long-standing pulsatile LH secretion induces the differentiation of
interstitial cells into testosterone-secreting Leydig cells, which, in
turn, exert a negative feedback control on LH secretion.

As puberty progresses, spermatogenesis is initiated and then

sustained by FSH and by testosterone produced by the Leydig
cells under LH control.
 A significant increase of plasma testosterone is found only
between Tanner pubertal stages P3 and P4.

Dihydrotestosterone shows a pattern similar to that of

testosterone, and

the proportion of dihydrotestosterone to testosterone

decreases gradually until adulthood, when
dihydrotestosterone levels are approximately 10% of those of
testosterone.
Puberty is completed usually within 3 to 4 years of its onset,

and the final height resulting from complete fusion of the

epiphyses occurs within approximately 2 years after menarche
Abnormal Puberty
•Delayed Puberty
•Early or Precocious Puberty
Delayed Puberty

CAUSES OF DELAYED PUBERTY

•Hypogonadotrophic
•Constitutional (familial, sporadic)
•Chronic illness (CF, Crohns Disease, Renal failure)
•Malnutrition (Anorexia, CF, coeliac disease)
•Exercise
•Tumours of pituitary/hypothalamus (craniopharyngioma)
•Hypothalamic syndromes (Laurence-Moon-Biedl)
•Hypothyroidism
•Suppression 20 to hyperthyroidism, hyperprolactinemia,
Cushing Syndrome.
Hypopituitarism
b. Hypergonadotrophic

•Congenital
Turner Syndrome
Klinefelters Syndrome

•Acquired
Irradiation / Chemotherapy
Surgery
Testicular torsion, trauma
Infection
Autoimmunity
•Precocious puberty

Causes:

•Onset of secondary sexual characteristics < 8yrs in girls

and < 9yrs in boys

•5 times more common in girls

•Usually benign central process – girls

•Pathological in ~ 50% in boys

Premature Thelarche/puberchy

•Thelarche – beginning of breast development

•Pubarche – first appearance of pubic hair

•It is more common in certain populations e.g asian / afro-

caribbean and more common than true precocious puberty.
Benign variants
 breast development in girls < 3yrs with spontaneous
regression

Pubic hair in boys and girls < 7yrs due to adrenal

androgen secretion in middle childhood
 Investigations
• Blood Tests (first line) • Second line
– CBC – GnRH assay
– FSH/LH – Beta –HCG
– Oest/Testosterone
– Adrenal androgens – Karyotype if indicated
– Prolactin
 Diagnostic Imaging
• Pelvic USS (ovarian tumours / cysts)
• Testicular USS (tumour)
• Adrenal USS (MRI / CT better if tumour considered)
• Bone Age (if within 1yr of CA, puberty not started or only just
started; if > 2yrs, puberty already started)
• Brain MRI in all males and patients with neurological signs or
symptoms)
 Management
• Treat systemic disease

• Psychological support

• Promote puberty / growth if necessary

– Low dose testosterone
– Ethinyloestradiol
THANK YOU
CLIMACTERIC AND MENOPAUSE
MENOPAUSE
Climacteric is the period in old age when the reproductive
system undergoes changes due to the decreased secretion of sex
hormones, estrogen and progesterone.

It occurs at the age of 45 to 55.

 Climacteric is accompanied by menopause.

Menopause

is defined as the period when permanent cessation of

menstruation takes place. OR

The permanent cessation of menstruation at the end of

reproductive life due to loss of ovarian follicular activity. It is the
point of time when last and final menstruation occurs.

.
 AGE OF MENOPAUSE
Age at which menopause occurs is genetically
predetermined and not related to age of menarche or age
at last pregnancy, lactation, use of oral pill, socioeconomic
condition, race, height or weight.

Normally, it occurs at the age of 45 to 55 years

In some women, the menstruation stops suddenly.

In others, the menstrual flow decreases gradually during

every cycle and finally it stops.

Sometimes irregular menstruation occurs with lengthening

or shortening of the period with less or more flow.

Early menopause may occur because of surgical removal

of ovaries (ovariectomy) or uterus (hysterectomy) as a part
of treatment for menstruation.
Usually, females with short menstrual cycle attain menopause
earlier than the females with longer cycle.

Cigarette smoking causes earlier onset of menopause

CAUSE OF MENOPAUSE

Due to advancement of age, the atrophy of ovaries occurs.

It leads to the cessation of menstrual cycle causing menopause.

HORMONE REGULATION OF MENOPAUSE

Throughout a woman’s sexual life, about 450 of the primordial
follicles grow into Graafian follicles and ovulate, while thousands of
the follicles degenerate.
At the age of 45 years, only few primordial follicles remain in
the ovary to be stimulated by FSH and LH.

Now, the production of estrogen by ovary decreases due to

the decrease in the number of primordial follicles.

When estrogen secretion becomes almost zero, FSH and LH

are continuously secreted.

When all the primordial follicles are atrophied, estrogen

secretion stops completely.
CHANGES DURING MENOPAUSE –POSTMENOPAUSAL SYNDROME

Postmenopausal syndrome is the group of symptoms that appear

in women immediately after menopause.

It is characterized by certain physical, physiological and

psychological changes.

The symptoms start appearing soon after the ovaries stop

functioning.
The major cause for the symptoms is the lack of estrogen and
progesterone.

Symptoms may persist till the body gets acclimatized to the

absence of estrogen and progesterone
SYMPTOMS

Symptoms do not appear in all women.

Some women develop mild symptoms and some

women develop severe symptoms, which last for few
months to few years.
Symptoms of postmenopausal syndrome:

1. Hot flashes characterized by extreme flushing of the skin:

Hot flashes start with discomfort in the abdomen and chill

followed by the feeling of heat spreading towards the head.
Then the face becomes red followed by sweating and
exhaustion.
2. Vasomotor instability: Wide fluctuation in blood pressure may
be present. Blood pressure increases suddenly and it comes back
to normal automatically.

3. Fatigue

4. Nervousness

5. Emotional outburst like crying and anger

6. Mental depression

7. Insomnia

8. Palpitation

9. Vertigo

10. Headache

11. Numbness or tingling sensation

12. Urogenital atrophy, also known as vaginal atrophy

1. Thinning of the membranes of genitals

2. Itching
3. Dryness
4. Bleeding
5. Watery discharge
6. Urinary frequency
7. Urinary incontinence
8. Urinary urgency
9. Increased susceptibility to inflammation and infection, for
example vaginal candidiasis and urinary tract infections
10. Vaginal dryness and vaginal atrophy
13. Long-term effects of estrogen lack such as osteoporosis and
atherosclerosis: Osteoporosis is the bone disease resulting in
reduction in bone mass.

And the bones become susceptible for fracture.

Atherosclerosis is the condition characterized by deposition of
cholesterol on the wall of the blood vessels.
14. Cardiovascular and cerebrovascular effects

1. Risk of Ischemic heart disease

2. Coronary artery disease and stroke increased
3. Atherosclerotic changes
4. Vasoconstriction
5. Thrombus formation
15. Skin, soft tissue

1. Breast atrophy
2. breast tenderness +/- swelling
3. Decreased elasticity of the skin
4. Formication (itching, tingling, burning, pins and
needles, or sensation of ants crawling on or under
the skin)
5. Skin thinning and becoming drier
16. Sexual
1. Dyspareunia or painful intercourse
2. Decreased libido
3. Problems reaching orgasm
DIAGNOSIS OF MENOPAUSE
Cessation of menstruation for consecutive 12 months
during climacteric.

Appearance of menopausal symptoms ‘hot flush’ and ‘night

sweats’.

Vaginal cytology – showing menstruation index of at least

10/85/5 (features of low oestrogen).

Serum oestradiol : < 20 pg/ml.

Serum FSH and LH: 40 mlU/ml (three values at weeks

interval required.
 MANAGEMENT
Prevention

Counselling

Treatment
NON-HORMONAL TREATMENT :

1. Nutritious diet
2. Supplementary calcium – daily intake of 1-1.5 gm
3. Exercise – weight bearing exercises, walking, jogging.
4. Vitamin D – supplementation of vitamin D3 (400-800 IU/day)
along with calcium can reduce osteoporosis and fractures.
5. Cessation of smoking and alcohol.
6. Bisphosphonates prevent osteoclastic bone resorption.
Commonly used drugs are etidronate and alendronate. It is
taken in empty stomach. Nothing should be taken by mouth for
at least 30 minutes after after oral dosing.
7. Fluoride prevents osteoporosis and increases bone matrix
Calcitonin inhibits bones resorption.
Selective oestrogen receptor modulators (SERMs) are tissue
specific in action. Of the SERMs, raloxifene has many mineral
density, reduce serum LDL and to raise HDL2 level.
Clonidine, an alpha adrenergic agonist may be used to reduce the
severity and duration of hot flushes.
Thiazides reduce urinary calcium excretion.
Paroxetine is effective to reduce hot flushes both the frequency
and severity.
Gabapentine is an analogue of gamma-amino-butyric acid. It is
found also to be effective.
Phytoestrogens containing isoflavones are found to lower the
incidence of vasomotor symptoms, osteoporosis and
cardiovascular disease.
Soy protein is also found effective to reduce vasomotor symptoms.
Soy protein acts as SERMs.
HORMONAL REPLACEMENT THERAPY (HRT)

 The HRT is indicated in menopausal woman to overcome the

short term and long term consequence of oestrogen deficiency.
INDICATIONS OF HORMONAL REPLACEMENT THERAPY:

1. Relief of menopausal symptoms

2. Prevention of osteoporosis
3. To maintain the quality of life in menopausal years
Special group of woman to whom HRT should be
prescribed:

1. Premature ovarian failure

2. Gonadal dysgenesis
3. Surgical or radiation menopause
Benefits of hormone replacement therapy:

1. Improvement of vasomotor symptoms (70-80%).

2. Improvement of urogenital atrophy.
3. Increase in bone mineral density (2-5%).
4. Decreased risk in vertebral and hip fractures (25-50%).
5. Reduction in colorectal cancer (20%).
6. Possibly cardio protection.
Risks of hormonal replacement therapy:

Endometrial cancer : when oestrogen is given alone to a woman

with intact uterus.

Breast cancer : combined oestrogen and progestin replacement

therapy.

Venous thrombotic (VTE) disease : use of combined oral

oestrogen and progestin.

Coronary heart disease : combined HRT therapy

Lipid metabolism: gallbladder disease

Dementia, Alzheimer disease are increased.
Contraindications to hormonal replacement therapy:

1. Undiagnosed genital tract bleeding

2. Oestrogen dependent neoplasm in the body
3. History of venous thromboembolism
4. Active liver disease
5. Gallbladder disease
DURATION OF HRT USE:

A short period of 3-5 years has been advised.

Reduction of dosage should be done as soon as possible.