Ammenorrhea

IsmailIsmail
Tasbeeeh Ur RahmanTasbeeeh Ur Rahman
AMENORRHEAAMENORRHEA

Is the absence or abnormal
cessation of the menses
PHYSIOLOGIALPHYSIOLOGIAL
PATHOLOGIALPATHOLOGIAL

CONTROL OFCONTROL OF MENSTRUAL CYCLEMENSTRUAL CYCLE
HYPOTHALAMUS
PITUITARY
ENDOCRINE
OVARIES
OUTFLOW TRACT
AXIS

CLASSIFICATION OF AMENORRHEACLASSIFICATION OF AMENORRHEA
PHYSIOLOGICALPHYSIOLOGICAL PATHOLOGICAL
Pre-puberty
Pregnancy related
Menopause
Primary
Secondary

 A patient is diagnosed withA patient is diagnosed with primary
amenorrhea ifif
 She has not reached menarche by age 14She has not reached menarche by age 14
without secondary sexual development.without secondary sexual development.
OR
 She has not reached menarche by age 16She has not reached menarche by age 16
with normal secondary sexualwith normal secondary sexual
development.development.
PATHOLOGICAL AMENORRHEAPATHOLOGICAL AMENORRHEA

Secondary amenorrhea if establishedif established
menses have ceased for longer thanmenses have ceased for longer than
 3 months if previous menses were regular3 months if previous menses were regular
OR
 6 months if previous menses were6 months if previous menses were
irregular.irregular.
PATHOLOGICAL AMENORRHEA contdPATHOLOGICAL AMENORRHEA contd..

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

Primary AmenorrheaPrimary Amenorrhea

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

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
 urinary retention.
Signs: Bluish bulging membrane at the
introitus

GONADAL DYSGENESIS (Turner’s syndrome)
 Chromosomal abnormalities ( 45,XO 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.
FSH is elevated due to lack of estrogen feed
back inhibition

ANDROGEN INSENSITIVITY (Testicular feminization)
 A syndrome found in patient with X, Y
chromosome but resistant to androgens
(androgen insensitivity.
 Has male karyotype (46,XY) with female
appearance.
Presentation: Female appearance with
 Female breast development
 Female external genitalia
 No axillary and pubic hair
 Primary amenorrhea
 Absent uterus
 Gonad are testes
Phenotype female
Genotype female
XY

HYPOTHALAMIC FAILURE (Kallmann’s syndrome)
Congenital disorder characterized by:
Hypogonadotropic hypogonadism
Eunuchoidal features
Anosmia or hyposmia
Primary amenorrhea
Uterus present but breast absent
Caused by defect in synthesis and/or
release of GnRH
Phenotype female
Genotype female

Secondary AmenorrheaSecondary Amenorrhea

- Physiological- Physiological--
The most common cause of secondaryThe most common cause of secondary
amenorrhea in reproductive age women isamenorrhea in reproductive age women is
pregnancypregnancy and this should always beand this should always be
excluded by physical exam and laboratoryexcluded by physical exam and laboratory
testing for the pregnancy hormone – betatesting for the pregnancy hormone – beta
HCG.HCG.

HYPOTHALAMUS-PITUITARY
OVARIAN
OUTFLOW TRACT
ENDOCRINE
Hypothyroidism
Cushing’s
Adrenal tumour
Ovarian tumour
)androgen(
Pituitary
adenoma
Sheehan’s
syndrome
Hypothalamic
Dysfunction
Medications
Premature ovarian
failure
PCOS
Surgical removal
Asherman’s
syndrome
Hysterectomy

POLYCYSTIC OVARIAN SYNDROME (PCOS)
PCOS accounts for 90% of cases of
oligoamenorrhea
The etiology is probably related to insulin
resistance, with a failure of normal follicular
development and ovulation
The classical picture – AMENORRHEA,
OBESITY, SUBINFERTILITY and HIRSUITISM

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 tumor, infarction,
thrombosis or inflammation.

PITUITARY CAUSES
Pituitary failure - It is usually the
acquired type as a result of trauma,
treatment of pituitary tumor or infarction
after massive blood loss ( Sheehan’s
syndrome )
Pituitary adenoma →
hyperprolactinemia which cause
secondary amenorrhea.

ENDOCRINE CAUSES
Thyroid disorder and Cushing’s
disease interfere with the normal
functioning of the
hypothalamic_pituitary_ovarian axis → present
with amenorrhea.
Androgen – secreting tumors of the
ovaries → cause secondary amenorrhea.

ANATOMICAL CAUSES
Usually due to previous surgery.
Commonest example:
Hysterectomy
Endometrial ablation
Asherman’s syndrome )damage to the
endometrium with adhesion formation,
Scarring(
Stenosis of the cervix following cone biopsy

PREMATURE OVARIAN FAILURE
Premature ovarian failure occurs in about 1%
before the age of 40.
Premature ovarian failure may be due to:
Chemotherapy and radiotherapy.
Autoimmune disease following viral infection
Following surgery for conditions such as
endometriosis

DRUGS CAUSING HYPERPROLACTINAEMIA
Hyperprolactinemia accounts for 20% of
cases of amenorrhea.
Prolactin inhibits GnRH release from the
hypothalamus
Drugs that may cause hyperprolactinemia:
1). Phenothiazines
2). Methyldopa
3). Cimetidine
4). Butyrophenones
5). Antihistamines

THE ASSESSMENTTHE ASSESSMENT
HISTORY
EXAMINATION
INVESTIGATIONS

HistoryHistory
A good history can reveal the etiologicA good history can reveal the etiologic
diagnosis in up to 85% of cases ofdiagnosis in up to 85% of cases of
amenorrhea.amenorrhea.
ASSESSMENTASSESSMENT

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 gynecological surgery
CLINICAL ASSESSMENTCLINICAL ASSESSMENT
- HISTORY- HISTORY--
ASK ABOUT
Menstrual cycle → age of menarche and previous
menstrual history
Previous pregnancies - severe PPH (Sheehan’s
syndrome)
Chronic illness

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

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

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

 BLOOD TESTSBLOOD TESTS
 ULTRASOUNDULTRASOUND
 CT scan of pituitaryCT scan of pituitary
 LAPAROSCOPYLAPAROSCOPY
 KAROTYPINGKAROTYPING
INVESTIGATINGINVESTIGATING
PRIMARY AMENORRHEAPRIMARY AMENORRHEA

PRIMARY AMENORRHEAPRIMARY AMENORRHEA
SITE OF DISORDER DIAGNOSIS INVESTIGATIONS
HYPOTHALAMUSHYPOTHALAMUS Hypothalamic-Hypothalamic-
hypogonadismhypogonadism
FSH, LH and estradiol - LowFSH, LH and estradiol - Low
PITUITARYPITUITARY Pituitary adenomaPituitary adenoma Prolactin – HighProlactin – High
OVARYOVARY Gonadal dygenesisGonadal dygenesis
))Turner’s syndromeTurner’s syndrome((
FSH and LH – HighFSH and LH – High
Estradiol – LowEstradiol – Low
Karyotype – 45 XOKaryotype – 45 XO
MULLERIAN TRACTMULLERIAN TRACT Absent uterusAbsent uterus
))Testicular feminizationTesticular feminization((
PCT – negativePCT – negative
Karyotyping – 46 XYKaryotyping – 46 XY
GENITAL TRACTGENITAL TRACT Imperforate hymenImperforate hymen FSH, LH, estardiol – normalFSH, LH, estardiol – normal
PCT – negativePCT – negative
Examination – imperforateExamination – imperforate
hymenhymen

Primary amenorrhea
vagina
no yes
congenitalcongenital
uterovaginaluterovaginal
agenesisagenesis
imperforate hymenimperforate hymen
complete transversecomplete 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
completecomplete
androgenandrogen
insensitivityinsensitivity
syndromesyndrome
+ -
high low

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

 Progesterone challenge testProgesterone challenge test
 TSH (thyroid stimulating hormone)TSH (thyroid stimulating hormone)
 FSH, LHFSH, LH
 Prolactin levelProlactin level
Once pregnancy has been excluded

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
FailureHypothalamic-pituitary
failure
ANOVULATION
Positive E-P
challenge test
Very high FSH
FSH normal + high LH → PCOS
High prolactin → pituitary tumour
NEGATIVE PREGNANCY TEST
Thyroid Function Test

SITE OF DISORDER DIAGNOSIS INVESTIGATIONS
HYPOTHALAMUSHYPOTHALAMUS Hypothalamic – failureHypothalamic – failure
Weight-related amenorrheaWeight-related amenorrhea
PITUITARYPITUITARY Pituitary adenomaPituitary adenoma
Sheehan syndromeSheehan syndrome
Prolactin – HighProlactin – High
FSH, LH and estradiol – LowFSH, LH and estradiol – Low
FSH, LH and estrogen - LowFSH, LH and estrogen - Low
ENDOCRINEENDOCRINE HypothyroidismHypothyroidism TSH – raised ; T4 – low or NTSH – raised ; T4 – low or N
OVARYOVARY Premature menopausePremature menopause
PCOSPCOS
FSH, LH – high ; EFSH, LH – high ; E – low– low
FSH – Normal ; LH - HighFSH – Normal ; LH - High
MULLERIAN TRACTMULLERIAN TRACT Asherman’s syndromeAsherman’s syndrome PCT – negativePCT – negative
HSG / HystereoscopyHSG / Hystereoscopy

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

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

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 gonadotropins 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

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

Ammenorrhea

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