Amenorrhea

1. Assoc Professor Dr MNM AZHARAssoc Professor Dr MNM AZHAR
Faculty of Medicine & Health SciencesFaculty of Medicine & Health Sciences
UNIMASUNIMAS
AMENORRHEAAMENORRHEA

2. AMENORRHEAAMENORRHEA
Is the absence or abnormal
cessation of the menses
PHYSIOLOGIALPHYSIOLOGIAL
AMENORRHEAAMENORRHEA
PATHOLOGIALPATHOLOGIAL
AMENORRHEAAMENORRHEA

3. CONTROL OFCONTROL OF MENSTRUAL CYCLEMENSTRUAL CYCLE
HYPOTHALAMUS
PITUITARY
ENDOCRINE
OVARIAN
OUTFLOW TRACT
AXIS

4. CLASSIFICATION OF AMENORRHEACLASSIFICATION OF AMENORRHEA
AMENORRHEA
PHYSIOLOGICAL PATHOLOGICAL
Pre-puberty
Pregnancy related
Menopause
Primary
Secondary

5. AMENORRHEAAMENORRHEA
A patient is diagnosed with A patient is diagnosed with primary
amenorrhea if she has not reached if she has not reached
menarche by age 16 with normal menarche by age 16 with normal
secondary sexual characteristics.secondary sexual characteristics.
Secondary amenorrhea if established if established
menses have ceased for longer than 6 menses have ceased for longer than 6
months without any physiological reasons.months without any physiological reasons.
PATHOLOGICAL AMENORRHEAPATHOLOGICAL AMENORRHEA

6. ETIOLOGY OF AMENORRHEAETIOLOGY OF AMENORRHEA
HYPOTHALAMUS
PITUITARY
ENDOCRINE
OVARIAN
OUTFLOW TRACT
AXIS
Congenital absent of
uterus and vagina
Vaginal atresia
Imperforate hymen
Asherman’s syndrome
Pituitary adenoma
Sheehan’s syndrome
Hypothalamic-hypogonadism
Weight related amenorrhea
(anorexia nervosa)
Hypothyroidism
Gonadal dysgenesis
Gonadal failure
PCOS

7. Etiology of AmenorrheaEtiology of Amenorrhea
Primary  
Gonadal failure (43%)Gonadal failure (43%)  
Congenital absence of uterus and vagina (15%)Congenital absence of uterus and vagina (15%)  
Constitutional delay (14%)Constitutional delay (14%)
Secondary   
Chronic anovulation (39%)Chronic anovulation (39%)
Hypothyroidism / hyperprolactinemia (20%)Hypothyroidism / hyperprolactinemia (20%)  
Weight loss/anorexia (16%)Weight loss/anorexia (16%)

8. Primary AmenorrheaPrimary Amenorrhea
Primary amenorrhea is 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

9. HYPOTHALAMUS-PITUITARY
OVARIAN
OUTFLOW TRACT
CHROMOSOME
MUTATION
Primary Amenorrhea
- ETIOLOGY -
Androgen
insensitivity
(testicular
feminization)
Hypothalamic
failure
(Kallmann’s
syndrome)
Turner’s syndrome
Gonadal
dysgenesis
Absent of uterus
Absent of vagina
Imperforate
hymen

10. OUT FLOW TRACT DISORDERS (Imperforate hymen)
Primary Amenorrhea
- ETIOLOGY -
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

11. GONADAL DYSGENESIS (Turner’s syndrome)
Primary Amenorrhea
- ETIOLOGY -
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.

12. ANDROGEN INSENSITIVITY (Testicular feminization)
Primary Amenorrhea
- ETIOLOGY -
A syndrome found in patient with X, Y chromosome
but resistant to androgens (androgen insensitivity.
Has male karyotype (45XY) with female appearance.
Presentation:
Female appearance with normal breast development
and external genitalia.
Primary amenorrhea , absent uterus
Gonad - testes
Phenotype female
Genotype female
XY

13. HYPOTHALAMIC FAILURE (Kallmann’s syndrome)
Primary Amenorrhea
- ETIOLOGY -
Congenital disorder characterized by:
1) Hypogonadotropic hypogonadism
2) Eunuchoidal features
3) Anosmia or hyposmia
4) Primary amenorrhea
Caused by defect in synthesis and/or release of
gonadorelin (LH releasing hormone)
Phenotype female
Genotype female

14. Secondary AmenorrheaSecondary Amenorrhea
Secondary amenorrhea is the absence of menstrual Secondary amenorrhea is the absence of menstrual
periods for 6 months in a woman who had periods for 6 months in a woman who had
previously been regular, or for 12 months in a previously been regular, or for 12 months in a
woman who had irregular periods without any woman who had irregular periods without any
physiological reasons.physiological reasons.

15. Secondary AmenorrheaSecondary Amenorrhea
- Physiological -- Physiological -
The most common cause of secondary The most common cause of secondary
amenorrhea in reproductive age women isamenorrhea in reproductive age women is
pregnancy pregnancy and this should always be and this should always be
excluded by physical exam and laboratory excluded by physical exam and laboratory
testing for the pregnancy hormone - HCG.testing for the pregnancy hormone - HCG.

16. HYPOTHALAMUS-PITUITARY
OVARIAN
OUTFLOW TRACT
ENDOCRINE
Secondary Amenorrhea
- ETIOLOGY -
Hypothyroidism
Cushing’s
Adrenal tumour
Ovarian tumour
(androgen)
Pituitary tumour
Sheehan’s
syndrome
Hypothalamic
dysfunction
Premature ovarian
failure
PCOS
Surgical removal
Asherman’s
syndrome
Hysterectomy

17. POLYCYSTIC OVARIAN SYNDROME (PCOS)
Secondary Amenorrhea
- ETIOLOGY -
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

18. HYPOTHALAMIC CAUSES
Secondary Amenorrhea
- ETIOLOGY -
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.

19. PITUITARY CAUSES
Secondary Amenorrhea
- ETIOLOGY -
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.

20. ENDOCRINE CAUSES
Secondary Amenorrhea
- ETIOLOGY -
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.

21. ANATOMICAL CAUSES
Secondary Amenorrhea
- ETIOLOGY -
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

22. PREMATURE OVARIAN FAILURE
Secondary Amenorrhea
- ETIOLOGY -
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

23. DRUGS CAUSING HYPERPROLACTINAEMIA
Secondary Amenorrhea
- ETIOLOGY -
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

24. THE ASSESSMENTTHE ASSESSMENT
HISTORY
EXAMINATION
INVESTIGATIONS

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

26. HistoryHistory
A good history can reveal the etiologic A good history can reveal the etiologic
diagnosis in up to 85% of cases of diagnosis in up to 85% of cases of
amenorrhea.amenorrhea.
ASSESSMENT

27. Hot flashes , decreased libido ® premature menopause
Certain medications
Weight change ® A large amount of weight loss (anorexia
nervosa)
Associate symptoms - Cushing's disease , hypothyroidism
Contraception
Previous gynaecological surgery
CLINICAL ASSESSMENT
- HISTORY -
ASK ABOUT
Menstrual cycle ® age of menarche and previous menstrual
history
Previous pregnancies - severe PPH (Sheehan’s syndrome)
Chronic illness

28. Secondary sexual characteristic
Features of Turner’s syndrome
ANDROGEN EXCESS ® hirsuitism (PCOS) – virilization (tumour)
Abdominal (haemato mera) and pelvic masses (ovarian tumour)
Breast examination ® may revealed galactorrhea,
Inspection of genitalia ® imperforate hymen, cervical stenosis
CLINICAL ASSESSMENT
- EXAMINATION -
CHECK FOR
BODY MASS INDEX (BMI) ® weight loss-related amenorrhea
BLOOD PRESSURE ® elevated in Cushing and PCOS
Vaginal examination ® blind vagina, vaginal atresia, absent of
uterus

29. If the history and physical exam are
suggestive of a certain etiology
The workup can sometimes be more The workup can sometimes be more
directeddirected
CLINICAL ASSESSMENT
- INVESTIGATIONS -

30. Some patients will not demonstrate any
obvious etiology for their amenorrhea on
history and physical examination
These patients can be worked up in a These patients can be worked up in a
logical manner using a stepwise logical manner using a stepwise
approach.approach.
CLINICAL ASSESSMENT
- INVESTIGATIONS -

31. BLOOD TESTS BLOOD TESTS
ULTRASOUNDULTRASOUND
CT scan of pituitary CT scan of pituitary
KAROTYPINGKAROTYPING
LAPAROSCOPYLAPAROSCOPY
INVESTIGATING
PRIMARY AMENORRHEA

32. INVESTIGATING
PRIMARY AMENORRHEA
FSH, LH, estardiol – normal
PCT – negative
Examination – imperforate
hymen
Imperforate hymenGENITAL TRACT
PCT – negative
Karyotyping – 46 XY
Absent uterus
(Testicular feminization)
MULLERIAN TRACT
FSH and LH – High
Estradiol – Low
Karyotype – 45 XO
Gonadal dygenesis
(Turner’s syndrome)
OVARY
Prolactin – High
FSH, LH and estradiol - Low
Pituitary adenomaPITUITARY
FSH, LH and estradiol - LowHypothalamic-hypogonadismHYPOTHALAMUS
INVESTIGATIONSDIAGNOSISSITE OF DISORDER

33. Primary amenorrhea
vagina
no yes
congenital uterovaginal congenital uterovaginal
agenesis agenesis
imperforate hymen imperforate hymen
complete transverse complete transverse
vaginal septumvaginal septum
Pubic hair
Estrogenized
breasts have
developed
Progesterone challenge
abnormal ovaries
abnormal hormonal stimulation
of normal ovaries
(Hypothalamic-hypogonadism)
FSH Level
Chromosome
Analysis
no
noyes
complete androgen complete androgen
insensitivity insensitivity
syndromesyndrome
+ -
high low

34. INVESTIGATINGINVESTIGATING
SECONDARY AMENORRHEASECONDARY AMENORRHEA
The most common cause of secondary The most common cause of secondary
amenorrhea in reproductive age women isamenorrhea in reproductive age women is
pregnancy and this should always be and this should always be
excluded by physical exam and laboratory excluded by physical exam and laboratory
testing for the pregnancy hormone - HCG.testing for the pregnancy hormone - HCG.

35. Progesterone challenge test Progesterone challenge test
TSH (thyroid stimulating hormone)TSH (thyroid stimulating hormone)
FSH, LH FSH, LH
Prolactin levelProlactin level
INVESTIGATING
SECONDARY AMENORRHEA
Once pregnancy has been excluded

36. FSH, LH and Thyroid function test
Progesterone challenge test
WITHDRAWAL
BLEEDING
NO WITHDRAWAL
BLEEDING
HYPOESTROGENIC
COMPROMISED
OUTFLOW TRACT
Negative E-P
challenge test
Normal FSH
Asherman’s syndrome
(HSG or hysteroscopy)
Normal or Low
FSH
Ovarian
Failure
Hypothalamic-pituitary
failure
ANOVULATION
Positive E-P
challenge test
Very high FSH
FSH normal + high LH ® PCOS
High prolactin ® pituitary tumour
NEGATIVE PREGNANCY TEST
INVESTIGATING SECONDAY AMENORRHEA

37. Ovarian failure
(premature menopause)
chromosomal
anomalies
autoimmune
disease
If the woman is under
30, a karyotype should
be performed to rule out
any mosaicism involving
a Y chromosome.
it is prudent to screen for
thyroid, parathyroid, and
adrenal dysfunction
If a Y chromosome is
found the gonads
should be surgically
excised.
Laboratory evidence of autoimmune
phenomenon is much more prevalent
than clinically significant disease
SECONADARY AMENORRHEA

38. Hypothalamic-pituitary Hypothalamic-pituitary
failurefailure
Patients who do not bleed after the progestin Patients who do not bleed after the progestin
challenge challenge
But do bleed after estrogen/progestin andBut do bleed after estrogen/progestin and
Have normal or low FSH and LH levelsHave normal or low FSH and LH levels
SECONDARY AMENORRHEA

39. INVESTIGATING
SECONDARY AMENORRHEA
PCT – negative
HSG / Hystereoscopy
Asherman’s syndromeMULLERIAN TRACT
FSH, LH – high ; E
2
– low
FSH – Normal ; LH - High
Premature menopause
PCOS
OVARY
TSH – raised ; T4 – low or NHypothyroidismENDOCRINE
Prolactin – High
FSH, LH and estradiol – Low
FSH, LH and estrogen - Low
Pituitary adenoma
Sheehan syndrome
PITUITARY
FSH, LH and estradiol - LowHypothalamic – failure
Weight-related amenorrhea
HYPOTHALAMUS
INVESTIGATIONSDIAGNOSISSITE OF DISORDER

40. TREATMENT OF
AMENORRHEA
The need for treatment depends on
Underlying causes
Need for regular periods
Trying to conceive (fertility
Need for contraception)

41. 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

42. 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

43. 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

44. AMENORRHEA
PROF DR MOHD AZHAR