Amenorrhea

Assoc Professor Dr MNM AZHARAssoc Professor Dr MNM AZHARFaculty of Medicine & Health SciencesFaculty of Medicine & Health Sciences

UNIMASUNIMAS

AMENORRHEAAMENORRHEA


Is the absence or abnormal cessation of the menses

PHYSIOLOGIALPHYSIOLOGIALAMENORRHEAAMENORRHEA

PATHOLOGIALPATHOLOGIALAMENORRHEAAMENORRHEA

CONTROL OFCONTROL OF MENSTRUAL CYCLEMENSTRUAL CYCLE

HYPOTHALAMUS

PITUITARY

ENDOCRINE

OVARIAN

OUTFLOW TRACTAXIS

CLASSIFICATION OF AMENORRHEACLASSIFICATION OF AMENORRHEA


PHYSIOLOGICALPHYSIOLOGICAL PATHOLOGICAL

Pre-pubertyPregnancy relatedMenopause

Primary

Secondary


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

ETIOLOGY OF AMENORRHEAETIOLOGY OF AMENORRHEA

HYPOTHALAMUS

PITUITARY

ENDOCRINE

OVARIAN

OUTFLOW TRACTAXIS

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

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%)

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

HYPOTHALAMUS-PITUITARY

OVARIAN

OUTFLOW TRACT

CHROMOSOMEMUTATION

Primary AmenorrheaPrimary Amenorrhea - ETIOLOGY- ETIOLOGY- -

Androgeninsensitivity

(testicularfeminization)

Hypothalamicfailure

(Kallmann’ssyndrome)

Turner’s syndromeGonadal

dysgenesis

Absent of uterusAbsent of vaginaImperforatehymen

OUT FLOW TRACT DISORDERS (Imperforate hymen)


Imperforate hymen represents one form of failure ofcomplete canalization of the vagina.

Most frequent obstructive anomaly of the female genital tract.

Presentation: primary amenorrhea associated withcyclical abdomen pain – abdominal swelling andurinary retention.

Signs: Bluish bulging membrane at the introitus

GONADAL DYSGENESIS (Turner’s syndrome)


Chromosomal abnormalities ( 45XO female)

Associated with streak ovarian tissue and primaryamenorrhea.

Presentation: primary amenorrhea associated withfeatures of Turner’s syndrome – short stature, webbed neck, increased carrying angle at the elbow and sexual infantilism.

ANDROGEN INSENSITIVITY (Testicular feminization)


A syndrome found in patient with X, Y chromosomebut 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 uterusGonad - testes

Phenotype female

Genotype female

XY

HYPOTHALAMIC FAILURE (Kallmann’s syndrome)


Congenital disorder characterized by:

1 (Hypogonadotropic hypogonadism2 (Eunuchoidal features3 (Anosmia or hyposmia

4 (Primary amenorrhea

Caused by defect in synthesis and/or release ofgonadorelin (LH releasing hormone)

Phenotype female

Genotype female

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.

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.

HYPOTHALAMUS-PITUITARY

OVARIAN

OUTFLOW TRACT

ENDOCRINE

Secondary AmenorrheaSecondary Amenorrhea - ETIOLOGY- ETIOLOGY- -

HypothyroidismCushing’s

Adrenal tumourOvarian tumour

(androgen)

Pituitary tumourSheehan’s

syndromeHypothalamicdysfunction

Premature ovarianfailurePCOSSurgical removal

Asherman’s syndromeHysterectomy

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 andovulation

The classical picture – AMENORRHEA, OBESE,SUBINFERTILITY and HIRSUITISM

HYPOTHALAMIC CAUSES


Hypothalamic dysfunction is a common cause (30%).

It is more often seen as a result of stress, weight lossand eating disorders

It may be due to tumour, infarction, thrombosis or inflammation.

PITUITARY CAUSES


Pituitary failure - It is usually the acquired type as the result of trauma, treatment of pituitary tumour orinfarction after massive blood loss ( Sheehan’s syndrome )

Pituitary tumour hyperprolactinaemia 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.

High level of thyroxine inhibit FSH release.

Androgen – secreting tumours of the ovaries cause secondary amenorrhea.

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

PREMATURE OVARIAN FAILURE


Premature ovarian failure occurs in about 1% beforethe 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

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 ASSESSMENTTHE ASSESSMENT

HISTORY

EXAMINATION

INVESTIGATIONS

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.

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.

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 gynaecological 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 mera) 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, absent of uterus

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


- 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 a These patients can be worked up in a logical manner using a stepwise logical manner using a stepwise

approach.approach.


- INVESTIGATIONS- INVESTIGATIONS- -

BLOOD TESTS BLOOD TESTS ULTRASOUNDULTRASOUND CT scan of pituitary CT scan of pituitary KAROTYPINGKAROTYPING LAPAROSCOPYLAPAROSCOPY

INVESTIGATINGINVESTIGATING

PRIMARY AMENORRHEAPRIMARY AMENORRHEA


PRIMARY AMENORRHEAPRIMARY AMENORRHEA

SITE OF DISORDERDIAGNOSISINVESTIGATIONS

HYPOTHALAMUSHYPOTHALAMUSHypothalamic-hypogonadismHypothalamic-hypogonadismFSH, LH and estradiol - LowFSH, LH and estradiol - Low

PITUITARYPITUITARYPituitary adenomaPituitary adenomaProlactin – HighProlactin – High

FSH, LH and estradiol - LowFSH, LH and estradiol - Low

OVARYOVARYGonadal dygenesisGonadal dygenesis

((Turner’s syndromeTurner’s syndrome))

FSH and LH – HighFSH and LH – High

Estradiol – LowEstradiol – Low

Karyotype – 45 XOKaryotype – 45 XO

MULLERIAN TRACTMULLERIAN TRACTAbsent uterusAbsent uterus

((Testicular feminizationTesticular feminization))

PCT – negativePCT – negative

Karyotyping – 46 XYKaryotyping – 46 XY

GENITAL TRACTGENITAL TRACTImperforate hymenImperforate hymenFSH, LH, estardiol – normalFSH, LH, estardiol – normal

PCT – negativePCT – negative

Examination – imperforate Examination – imperforate hymenhymen

Primary amenorrhea

vagina

no yes

congenital uterovaginal congenital uterovaginal agenesisagenesis imperforate hymenimperforate hymen

complete transverse complete transverse vaginal septumvaginal septum

Pubic hair

Estrogenized

breasts have developed

Progesterone challenge

abnormal ovariesabnormal hormonal stimulation

of normal ovaries)Hypothalamic-hypogonadism(

FSH Level

Chromosome Analysis

no

noyes

complete androgen complete androgen insensitivity insensitivity syndromesyndrome

+ -

high low


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.

Progesterone challenge test Progesterone challenge test TSH (thyroid stimulating hormone)TSH (thyroid stimulating hormone) FSH, LH FSH, LH Prolactin levelProlactin level


SECONDARY AMENORRHEASECONDARY AMENORRHEA Once pregnancy has been excluded

FSH, LH and Thyroid function test Progesterone challenge test

WITHDRAWAL

BLEEDING

NO WITHDRAWAL

BLEEDING

HYPOESTROGENIC COMPROMISED OUTFLOW TRACT

Negative E-Pchallenge test

Normal FSH

Asherman’s syndrome

)HSG or hysteroscopy(

Normal or Low FSH

Ovarian FailureHypothalamic-pituitary

failure

ANOVULATIONPositive E-P

challenge test

Very high FSH

FSH normal + high LH PCOSHigh prolactin pituitary tumour

NEGATIVE PREGNANCY TEST

INVESTIGATING SECONDAY AMENORRHEA

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

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


SECONDARY AMENORRHEASECONDARY AMENORRHEA SITE OF DISORDERDIAGNOSISINVESTIGATIONS

HYPOTHALAMUSHYPOTHALAMUSHypothalamic – failureHypothalamic – failure

Weight-related amenorrheaWeight-related amenorrhea

FSH, LH and estradiol - LowFSH, LH and estradiol - Low

PITUITARYPITUITARYPituitary 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

ENDOCRINEENDOCRINEHypothyroidismHypothyroidismTSH – raised ; T4 – low or NTSH – raised ; T4 – low or N

OVARYOVARYPremature menopausePremature menopause

PCOSPCOS

FSH, LH – high ; EFSH, LH – high ; E2 2 – low– low

FSH – Normal ; LH - HighFSH – Normal ; LH - High

MULLERIAN TRACTMULLERIAN TRACTAsherman’s syndromeAsherman’s syndromePCT – negativePCT – negative

HSG / HystereoscopyHSG / Hystereoscopy

TREATMENT OF TREATMENT OF


The need for treatment depends on

Underlying causes

Need for regular periods

Trying to conceive (fertility

Need for contraception(


AMENORRHEAAMENORRHEA 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


AMENORRHEAAMENORRHEA 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


AMENORRHEAAMENORRHEA 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 aremethod of choice


PROF DR MOHD AZHAR

Education

Amenorrhea