AMENORRHEA

DR.AHMED REZK
Professor Of Obstetrics And Gynecology
AL-AZHAR UNIVERSITY
CONTROL OF MENSTRUAL CYCLE

HYPOTHALAMUS

PITUITARY

ENDOCRINE

OVARIAN

OUTFLOW TRACT
AXIS
 CNS-Hypothalamus-Pituitary
Ovary-uterus Interaction
Neural control Chemical control

Dopamine Norepiniphrine Endorphines

(-) (+) (-)

Hypothalamus
Gn-RH
± Ant. pituitary ? –
FSH, LH
Estrogen Ovaries Progesterone

Uterus

Menses
pubertal changes- Marshall & Tanner
Regular sequence of events between ages of 10-16 yrs in girls

GROWTH SPURT 14 - 8 yrs 9) yrs) 6

- 10 cm / yr peak
2.5 yrs duration

BREAST GROWTH (Thelarche) 8 - 13 yrs 11) yrs(

PUBIC HAIR (Pubarche) 9 - 13 yrs

1st Pubertal Sign in 25%

AXILLARY HAIR (Adrenarche) 9.5 - 15 yrs

may follow menarche

MENSTRUATION (Menarche) 10 - 16 yrs (13 yrs)

AMENORRHEA

Is the absence or abnormal

cessation of the menses

PHYSIOLOGIAL PATHOLOGIAL
AMENORRHEA AMENORRHEA
CLASSIFICATION OF AMENORRHEA

AMENORRHEA

PHYSIOLOGICAL PATHOLOGICAL

Pre-puberty Primary
Pregnancy related
Menopause Secondary
Prim ary & Second ary

Primary S econ dary

 ETIOLOGY OF AMENORRHEA

Hypothalamic-hypogonadism
HYPOTHALAMUS
Weight related amenorrhea
(anorexia nervosa) Pituitary adenoma

PITUITARY Sheehan’s syndrome

ENDOCRINE Hypothyroidism
Gonadal dysgenesis

Gonadal failure OVARIAN Congenital absent of

uterus and vagina
PCOS
Vaginal atresia
OUTFLOW TRACT
AXIS Imperforate hymen

Asherman’s syndrome
Etiology of Amenorrhea

Primary
• Gonadal failure (43%)
• Congenital absence of uterus and vagina (15%)
• Constitutional delay (14%)

Secondary
• Chronic anovulation (39%)
• Hypothyroidism / hyperprolactinemia (20%)
• Weight loss/anorexia (16%)
Primary Amenorrhea
Primary amenorrhea is the failure to start
menstruation by age of 16 in a girl with normal
secondary sexual characteristics OR by the age of
14 where there is a failure to develop secondary
sexual characteristics
 Primary Amenorrhea
- ETIOLOGY -
Hypothalamic
CHROMOSOME HYPOTHALAMUS-PITUITARY failure
MUTATION (Kallmann’s
syndrome)
Androgen
insensitivity
(testicular
feminization)

Turner’s syndrome OVARIAN Absent of uterus

Gonadal Absent of vagina
dysgenesis OUTFLOW TRACT Imperforate
hymen
 Primary Amenorrhea
- ETIOLOGY -
OUT FLOW TRACT DISORDERS (Imperforate hymen)

Imperforate hymen represents one form of failure of

complete canalization of the vagina.

Most frequent obstructive anomaly of the female

genital tract.

Presentation: primary amenorrhea associated with

cyclical abdomen pain – abdominal swelling and
urinary retention.

Signs: Bluish bulging membrane at the introitus

 Cryptomenorrhea
Outflow obstruction to menstrual blood
- Imperforate hymen
- Transverse Vaginal septum with functioning uterus
- Isolated Vaginal agenesis with functioning uterus
- Isolated Cervical agenesis with functioning uterus

- Intermittent abdominal pain

- Possible difficulty with micturition
- Possible lower abdominal swelling
- Bulging bluish membrane at the introitus or absent
vagina (only dimple)
cryptomenorrhea

hematocolpos
hematometra

17
Imperforate hymen
 Primary Amenorrhea
- ETIOLOGY -
GONADAL DYSGENESIS (Turner’s syndrome)

Chromosomal abnormalities ( 45XO female)

Associated with streak ovarian tissue and primary

amenorrhea.

Presentation: primary amenorrhea associated with

features of Turner’s syndrome – short stature,
webbed neck, increased carrying angle at the elbow
and sexual infantilism.
 Turner’s syndrome
High FSH and LH levels.
• Bilateral streaked gonads.
• Karyotype - 80 % 45, X0
- 20% mosaic forms (46XX/45X0)
• Treatment: HRT

(Classic 45-XO) Mosaic (46-XX / 45-XO)

Ovarian dysgenesis
 Primary Amenorrhea
- ETIOLOGY -
ANDROGEN INSENSITIVITY (Testicular feminization)
Phenotype female

A syndrome found in patient with X, Y chromosome

but resistant to androgens (androgen insensitivity.

Has male karyotype (45XY) with female appearance.

Genotype female

Presentation:
Female appearance with normal breast development
and external genitalia.
XY Primary amenorrhea , absent uterus
Gonad - testes
 Primary Amenorrhea
- ETIOLOGY -
HYPOTHALAMIC FAILURE (Kallmann’s syndrome)
Phenotype female
Congenital disorder characterized by:

1) Hypogonadotropic hypogonadism
2) Eunuchoidal features
3) Anosmia or hyposmia
Genotype female
4) Primary amenorrhea

Caused by defect in synthesis and/or release of

gonadorelin (LH releasing hormone)
 Secondary
Amenorrhea
Secondary amenorrhea is the absence of menstrual
periods for 6 months in a woman who had
previously been regular, or for 12 months in a
woman who had irregular periods without any
physiological reasons.
 Secondary
Amenorrhea
- Physiological -
The most common cause of secondary
amenorrhea in reproductive age women is
pregnancy and this should always be
excluded by physical exam and laboratory
testing for the pregnancy hormone - HCG.
 Secondary Amenorrhea
- ETIOLOGY -

ENDOCRINE HYPOTHALAMUS-PITUITARY
Pituitary tumour
Hypothyroidism Sheehan’s
Cushing’s syndrome
Adrenal tumour Hypothalamic
Ovarian tumour dysfunction
(androgen)

Premature ovarian OVARIAN

failure Asherman’s
PCOS OUTFLOW TRACT syndrome
Surgical removal Hysterectomy
 Secondary Amenorrhea
- ETIOLOGY -
POLYCYSTIC OVARIAN SYNDROME (PCOS)

PCOS accounts for 90% of cases of oligoamenorrhea

Also known as Stein-Leventhal syndrome

The etiology is probably related to insulin resistance,

with a failure of normal follicular development and
ovulation

The classical picture – AMENORRHEA, OBESE,

SUBINFERTILITY and HIRSUITISM
 Secondary Amenorrhea
- ETIOLOGY -
HYPOTHALAMIC CAUSES

Hypothalamic dysfunction is a common cause (30%).

It is more often seen as a result of stress, weight loss

and eating disorders

It may be due to tumour, infarction, thrombosis or

inflammation.
 Secondary Amenorrhea
- ETIOLOGY -
PITUITARY CAUSES

Pituitary failure - It is usually the acquired type as

the result of trauma, treatment of pituitary tumour or
infarction after massive blood loss ( Sheehan’s
syndrome )

Pituitary tumour  hyperprolactinaemia which

cause secondary amenorrhea.
 Secondary Amenorrhea
- ETIOLOGY -
ENDOCRINE CAUSES

Thyroid disorder and Cushing’s disease interfere

with the normal functioning of the hypothalamic -
pituitary – ovarian axis  present with amenorrhea.

High level of thyroxine inhibit FSH release.

Androgen – secreting tumours of the ovaries 

cause secondary amenorrhea.
 Secondary Amenorrhea
- ETIOLOGY -
ANATOMICAL CAUSES

Usually due to previous surgery.

Commonest example:
1). Hysterectomy
2). Endometrial ablation
3). Asherman’s syndrome (damage to the
endometrium with adhesion formation)
4). Stenosis of the cervix following cone biopsy
 Secondary Amenorrhea
- ETIOLOGY -
PREMATURE OVARIAN FAILURE

Premature ovarian failure occurs in about 1% before

the age of 40.

Premature ovarian failure may be due to:

1). Chemotherapy and radiotherapy.
2). Autoimmune disease following viral infection
3). Following surgery for conditions such as
endometriosis
 Secondary Amenorrhea
- ETIOLOGY -
DRUGS CAUSING HYPERPROLACTINAEMIA

Hyperprolactinaemia accounts for 20% of cases of

amenorrhea.

Prolactin inhibits GnRH release from the hypothalamus

Drugs that may cause hyperprolactinaemia:

1). Phenothiazines
2). Methyldopa
3). Cimetidine
4). Butyrophenones
5). Antihistamines
THE ASSESSMENT
HISTORY

EXAMINATION

INVESTIGATIONS
ASSESSMENT
The most common cause of secondary
amenorrhea in reproductive age women is
pregnancy and this should always be
excluded by physical exam and laboratory
testing for the pregnancy hormone - HCG.
 ASSESSMENT

History
A good history can reveal the etiologic diagnosis in
up to 85% of cases of amenorrhea.
 CLINICAL ASSESSMENT
- HISTORY -
ASK ABOUT
Menstrual cycle  age of menarche and previous menstrual
history
Previous pregnancies - severe PPH (Sheehan’s syndrome)

Weight change  A large amount of weight loss (anorexia

nervosa)
Hot flashes , decreased libido  premature menopause
Certain medications
Contraception
Associate symptoms - Cushing's disease , hypothyroidism

Previous gynaecological surgery

Chronic illness
 CLINICAL ASSESSMENT
- EXAMINATION -
CHECK FOR
BODY MASS INDEX (BMI)  weight loss-related amenorrhea

BLOOD PRESSURE  elevated in Cushing and PCOS

ANDROGEN EXCESS  hirsuitism (PCOS) – virilization (tumour)

Secondary sexual characteristic

Features of Turner’s syndrome
Breast examination  may revealed galactorrhea,
Abdominal (haemato mera) and pelvic masses (ovarian tumour)

Inspection of genitalia  imperforate hymen, cervical stenosis

Vaginal examination  blind vagina, vaginal atresia, absent of
uterus
 CLINICAL ASSESSMENT
- INVESTIGATIONS -

If the history and physical exam are

suggestive of a certain etiology

The workup can sometimes be more

directed
 CLINICAL ASSESSMENT
- INVESTIGATIONS -

Some patients will not demonstrate any

obvious etiology for their amenorrhea on
history and physical examination

These patients can be worked up in a logical

manner using a stepwise approach.
 INVESTIGATING
PRIMARY AMENORRHEA

• BLOOD TESTS

• ULTRASOUND
• CT scan of pituitary
• KAROTYPING
• LAPAROSCOPY
 INVESTIGATING
PRIMARY AMENORRHEA
INVESTIGATIONS DIAGNOSIS SITE OF DISORDER
FSH, LH and estradiol - Low Hypothalamic-hypogonadism HYPOTHALAMUS

Prolactin – High Pituitary adenoma PITUITARY

FSH, LH and estradiol - Low
FSH and LH – High Gonadal dygenesis OVARY
Estradiol – Low (Turner’s syndrome)
Karyotype – 45 XO
PCT – negative Absent uterus MULLERIAN TRACT
Karyotyping – 46 XY (Testicular feminization)
FSH, LH, estardiol – normal Imperforate hymen GENITAL TRACT
PCT – negative
Examination – imperforate
hymen
 Primary amenorrhea

vagina breasts have

developed
no yes no

Pubic hair
Progesterone challenge
yes no
congenital uterovaginal
+ -
agenesis complete androgen Estrogenized FSH Level
imperforate hymen
insensitivity
complete transverse
syndrome
vaginal septum
high low
abnormal hormonal stimulation
Chromosome abnormal ovaries of normal ovaries
Analysis (Hypothalamic-hypogonadism)
 INVESTIGATING
SECONDARY AMENORRHEA

The most common cause of secondary

amenorrhea in reproductive age women is
pregnancy and this should always be
excluded by physical exam and laboratory
testing for the pregnancy hormone - HCG.
 INVESTIGATING
SECONDARY AMENORRHEA
Once pregnancy has been excluded

• Progesterone challenge test

• TSH (thyroid stimulating hormone)
• FSH, LH
• Prolactin level
INVESTIGATING SECONDAY AMENORRHEA
NEGATIVE PREGNANCY TEST

FSH, LH and Thyroid function test

Progesterone challenge test

WITHDRAWAL NO WITHDRAWAL
BLEEDING BLEEDING

HYPOESTROGENIC COMPROMISED
ANOVULATION OUTFLOW TRACT
Positive E-P
FSH normal + high LH  PCOS challenge test Negative E-P
High prolactin  pituitary tumour challenge test
Normal or Low Very high FSH
FSH Normal FSH

Ovarian
Asherman’s syndrome
Hypothalamic-pituitary Failure
failure (HSG or hysteroscopy)
SECONADARY AMENORRHEA

Ovarian failure
(premature menopause)
chromosomal
autoimmune
anomalies
disease

If the woman is under

30, a karyotype should
be performed to rule out it is prudent to screen for
any mosaicism involving thyroid, parathyroid, and
a Y chromosome. adrenal dysfunction

If a Y chromosome is Laboratory evidence of autoimmune

found the gonads phenomenon is much more prevalent
should be surgically than clinically significant disease
excised.
SECONDARY AMENORRHEA

Hypothalamic-pituitary
failure

• Patients who do not bleed after the progestin challenge

• But do bleed after estrogen/progestin and

• Have normal or low FSH and LH levels

 INVESTIGATING
SECONDARY AMENORRHEA
INVESTIGATIONS DIAGNOSIS SITE OF DISORDER
FSH, LH and estradiol - Low Hypothalamic – failure HYPOTHALAMUS
Weight-related amenorrhea
Prolactin – High Pituitary adenoma PITUITARY
FSH, LH and estradiol – Low

FSH, LH and estrogen - Low Sheehan syndrome

TSH – raised ; T4 – low or N Hypothyroidism ENDOCRINE

FSH, LH – high ; E2 – low Premature menopause OVARY

FSH – Normal ; LH - High PCOS

PCT – negative Asherman’s syndrome MULLERIAN TRACT
HSG / Hystereoscopy
 TREATMENT OF
AMENORRHEA
The need for treatment depends on

Underlying causes

Need for regular periods

Trying to conceive (fertility

Need for contraception)

 TREATMENT OF
AMENORRHEA
Underlying causes
PITUITARY TUMOUR  Bromocryptine / Surgery

ANDROGEN producing tumour of ovary  Surgery

TESTICULAR FEMINIZATION  removed gonad + HRT

TURNER’S syndrome  HRT

IMPERFORATE HYMEN  surgical incision

THYROID disease – appropriate medical treatment

EATING DISORDERS  referred to psychiatrist

PCOS  appropriate treatment

ASHERMAN’s syndrome  breaking down adhesion + insert IUCD

 TREATMENT OF
AMENORRHEA
TRYING TO CONCEIVE
The prognosis for women with confirmed ovarian failure is poor.

ANOVULATION  response well with ovulation induction treatment

PCOS  ovulation may resume with weight reduction – fertility drugs
- use of gonadotrophins or ovarian drilling.

HYPERPROLACTINAEMIA  respond to treatment with dopamine

agonist.

HYPOTHALAMIC DYSFUNCTION  maintenance of normal weight

and change of lifestyle

ASHERMAN’S syndrome  breaking down adhesion + insert IUCD

 TREATMENT OF
AMENORRHEA
WANT REGULAR PERIOD
The use of

1): COMBINED ORAL CONTRACEPTIVE

2): HRT

NEED CONTRACEPTION
Confirmed ovarian failure will not required contraception

Women requiring contraception  oral contraceptives are

method of choice