SECONDARY AMENORRHEA Dr Hanaa Alani. AMENORRHEA Is the absence or abnormal cessation of the menses PHYSIOLOGIALAMENORRHEAPATHOLOGIALAMENORRHEA

SECONDARY SECONDARY AMENORRHEAAMENORRHEA

Dr Hanaa Alani

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

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.previously been regular.

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

Most common etiologiesMost common etiologies::Ovarian disease – 40%Ovarian disease – 40%

Hypothalamic dysfunction – 35%Hypothalamic dysfunction – 35%Pituitary disease – 19%Pituitary disease – 19%

Uterine disease – 5%Uterine disease – 5%Other – 1%Other – 1%

Secondary Secondary Amenorrhea/Oligomenorrhea: EtiologyAmenorrhea/Oligomenorrhea: Etiology

PregnancyPregnancyThyroid diseaseThyroid diseaseHyperprolactinemiaHyperprolactinemiaProlactinomaProlactinomaBreastfeeding, Breast stimulationBreastfeeding, Breast stimulationMedication (i.e. Antipsychotics, Antidepressants)Medication (i.e. Antipsychotics, Antidepressants)

Hypergonadotropic hypogonadismHypergonadotropic hypogonadismPostmenopausal ovarian failurePostmenopausal ovarian failurePremature ovarian failurePremature ovarian failure

Hypogonadotropic hypogonadismHypogonadotropic hypogonadismFunctional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa)Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa)CNS tumor (i.e. Craniopharyngioma)CNS tumor (i.e. Craniopharyngioma)Sheehan’s syndromeSheehan’s syndromeChronic illnessChronic illness

NormogonadotropicNormogonadotropicOutflow tract obstruction (i.e. Asherman’s syndrome, Cervical stenosis)Outflow tract obstruction (i.e. Asherman’s syndrome, Cervical stenosis)Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease, CAH)Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease, CAH)

Secondary Secondary Amenorrhea/Oligomenorrhea: EtiologyAmenorrhea/Oligomenorrhea: Etiology

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

11--Uterine defectUterine defect

Asherman`s syndromeAsherman`s syndromeThis is intrauterine synechiaeThis is intrauterine synechiae

**withdrawal beeding after hormonal test is negativewithdrawal beeding after hormonal test is negative

**history of D&C after delivery or termination of history of D&C after delivery or termination of pregnancy other cauese TB or schistosomiasispregnancy other cauese TB or schistosomiasis

**normal ovulatory cycle & premenstrual symptomsnormal ovulatory cycle & premenstrual symptoms

Patients with Asherman`s syndrome may evaluated by Patients with Asherman`s syndrome may evaluated by HSG & transvaginal USHSG & transvaginal US

TREATMENTTREATMENT

**hysteroscopic treatment with excision of synechiaehysteroscopic treatment with excision of synechiae

**mainaining of seperation of uterine walls by insertion mainaining of seperation of uterine walls by insertion of a large inert IUCD such as a Lippes loopof a large inert IUCD such as a Lippes loop

The result of treatment are often disappointing in term The result of treatment are often disappointing in term of subsequent fertilityof subsequent fertility

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

22--Premature ovarian failurePremature ovarian failure

Ovarian failure before 40 yearsOvarian failure before 40 years

Ovarian failure before 30 years may be due to chromosomal disorders . Ovarian failure before 30 years may be due to chromosomal disorders . Karyotyping is done to check for mosaicism ( some cells have Y chromosme) Karyotyping is done to check for mosaicism ( some cells have Y chromosme) gonadectomy is indicated to prevent malignant transformationgonadectomy is indicated to prevent malignant transformation

Other causes of premature ovarian failureOther causes of premature ovarian failure

Ovarian injury from surgery, radiation or chemotherapy, galactocaemia Ovarian injury from surgery, radiation or chemotherapy, galactocaemia &autoimmunity&autoimmunity

When premature ovarian failure is secondary to autoimmunity other endocrine When premature ovarian failure is secondary to autoimmunity other endocrine organs could be affectedorgans could be affected

InvestigationsInvestigations

FBS for diabetesFBS for diabetes

Free thyroxine, TSH for hypothyroidismFree thyroxine, TSH for hypothyroidism

Serum calcium for hypoparathyroidismSerum calcium for hypoparathyroidism

Fasting morning cortisolFasting morning cortisol

Treatment of premature ovarian failureTreatment of premature ovarian failureBy hormone therapy (estrogen & progesteroneBy hormone therapy (estrogen & progesterone))

DRUGS CAUSING HYPERPROLACTINAEMIA


Hyperprolactinaemia accounts for 20% of cases of amenorrhea.

Prolactin inhibits GnRH release from the hypothalamus

Drugs may cause hyperprolactinaemia:

33--Amenorrhea with hyperprolactinaemiaAmenorrhea with hyperprolactinaemiaGalactorrhea is the most frequently observed abnormalities associated with Galactorrhea is the most frequently observed abnormalities associated with hyperprolactinemiahyperprolactinemiaHyperprolactinemia that is sever or associated with menstrual disturbances or Hyperprolactinemia that is sever or associated with menstrual disturbances or galactorhea should be confirmed by a second test, TSH should be tested for galactorhea should be confirmed by a second test, TSH should be tested for hypothyroidismhypothyroidismIf clinically significant hyperprolactinaemia is not explained by hypothyroidism If clinically significant hyperprolactinaemia is not explained by hypothyroidism or drug use a CT or MRI scan of sella turcica should be performedor drug use a CT or MRI scan of sella turcica should be performedDrugs that may cause hyperprolactinaemia includesDrugs that may cause hyperprolactinaemia includes

11--tranqulizerstranqulizers22--antidepressantsantidepressants

33--antihypertensivesantihypertensives44--narcoticsnarcotics

55--metaclopramidemetaclopramide

Mechanisms that produce Mechanisms that produce Prolactin Prolactin1 - Normally dopamine suppresses prolactin 1 - Normally dopamine suppresses prolactin production. If a mass compresses the stalk of the production. If a mass compresses the stalk of the pituitary, the dopamine feedback pathway is pituitary, the dopamine feedback pathway is interrupted and it can no longer inhibit prolactin interrupted and it can no longer inhibit prolactin prolactin levels. Also,GnRH will not be able to pass prolactin levels. Also,GnRH will not be able to pass through and there will be through and there will be LH and LH and FSH. If there is FSH. If there is prolactin and prolactin and LH & FSH LH & FSH

there may be there may be E2 (Estradiol) levels - consider E2 (Estradiol) levels - consider hormone replacement therapy. hormone replacement therapy.

2 - Hyperprolactinemia may also be caused by 2 - Hyperprolactinemia may also be caused by psychoactive drugs which suppress dopamine. psychoactive drugs which suppress dopamine. Even so, you will still see Even so, you will still see FSH & LH levels. FSH & LH levels.

3 - Prolactin secreting adenomas produce 3 - Prolactin secreting adenomas produce excess prolactin excess prolactin levels levels

Two types of Prolactin Secreting Two types of Prolactin Secreting AdenomasAdenomas

MicroadenomasMicroadenomas vs. vs. MacroadenomasMacroadenomas

< <1010 mmmm < 10 mm < 10 mm diagnosed on MRIdiagnosed on MRI– –

important to do important to do Associated with visual symptomsAssociated with visual symptoms

Very benign Very benign and headaches and headachesTreat symptoms only – amenorrhea Treat symptoms only – amenorrhea Must be treated Must be treated

Follow up MRIs every 1-2 yrs to check Follow up MRIs every 1-2 yrs to check surgical treatment surgical treatment

Bromocriptine agonistBromocriptine agonist– – may shrink adenoma may shrink adenoma

for additional growth for additional growth

Radiation - works well but may Radiation - works well but may cause panhypopituitarism. cause panhypopituitarism.

Treatment Treatment of Hyperprolactinemiaof HyperprolactinemiaDopamine agonist therapy - (Cabegolin,Bromocriptine) - most Dopamine agonist therapy - (Cabegolin,Bromocriptine) - most common. This should induce ovulation and shrink the common. This should induce ovulation and shrink the adenoma. With drug induced hyperprolactinemia, adenoma. With drug induced hyperprolactinemia, bromocriptine may counter the effects of the anti-depressent bromocriptine may counter the effects of the anti-depressent medicationsmedications..

If it is a macroadenoma, transphenoidal resection may be done. If it is a macroadenoma, transphenoidal resection may be done. This will result inThis will result in

resumption of ovulation for 40% of patients. Only 10-50% will resumption of ovulation for 40% of patients. Only 10-50% will have a long tercure with the surgery. have a long tercure with the surgery.

Response to radiation can be very slow.Response to radiation can be very slow.If a patient has a microadenoma or other causes of If a patient has a microadenoma or other causes of hyperprolactinemia, birth control pills may be used to bring on hyperprolactinemia, birth control pills may be used to bring on regular periods and to correct the galactorrhea. If a woman regular periods and to correct the galactorrhea. If a woman wants to try and have a baby you can try ovulation induction.wants to try and have a baby you can try ovulation induction.

Goals of Treatment: Goals of Treatment: regulate menses, prevent endometrial regulate menses, prevent endometrial hyperplasia, induce ovulation for pregnancy, improve hyperplasia, induce ovulation for pregnancy, improve hirsutism (excessive body hair in a masculine pattern of hirsutism (excessive body hair in a masculine pattern of distribution due to hereditary or hormonal factors.)distribution due to hereditary or hormonal factors.)

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

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

ANDROGEN EXCESS hirsuitism (PCOS) – virilization (tumour)

Abdominal (haemato mera) and pelvic masses (ovarian tumour)

Breast examination may revealed galactorrhea ,

Inspection of genitalia cervical stenosis


- EXAMINATION- EXAMINATION- - CHECK FOR

BODY MASS INDEX (BMI) weight loss-related amenorrhea

BLOOD PRESSURE elevated in Cushing and PCOS

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- -

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.

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

Progestin challenge testProgestin challenge testMedroxyprogesterone acetate 10 mg daily for 10 daysMedroxyprogesterone acetate 10 mg daily for 10 days

IF withdrawal bleed occurs – Not outflow tract obstructionIF withdrawal bleed occurs – Not outflow tract obstruction

IF no withdrawal bleed occurs – Estrogen/Progestin challenge IF no withdrawal bleed occurs – Estrogen/Progestin challenge testtest

Estrogen/Progestin challenge testEstrogen/Progestin challenge testOral conjugated estrogen 0.625 – 2.5 mg daily for 35 daysOral conjugated estrogen 0.625 – 2.5 mg daily for 35 days

Medroxyprogesterone acetate 10 mg daily for 26-35 daysMedroxyprogesterone acetate 10 mg daily for 26-35 days

IF no withdrawal bleed occurs – Endometrial scarringIF no withdrawal bleed occurs – Endometrial scarringHysterosalpingogram or Hysteroscopy to evaluate endometrial cavityHysterosalpingogram or Hysteroscopy to evaluate endometrial cavity

Secondary Secondary Amenorrhea/Oligomenorrhea: Amenorrhea/Oligomenorrhea:

EvaluationEvaluation

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

Evaluation of hyperandrogenismEvaluation of hyperandrogenismSymptoms: hirsutism, acne, alopecia, masculinization, and virilizationSymptoms: hirsutism, acne, alopecia, masculinization, and virilization

Differential diagnosisDifferential diagnosis::

Adrenal disorders: Atypical congenital adrenal hyperplasia (CAH), Adrenal disorders: Atypical congenital adrenal hyperplasia (CAH), Cushing’s syndrome, Adrenal neoplasmCushing’s syndrome, Adrenal neoplasm

Ovarian disorders: PCOS, Ovarian neoplasmsOvarian disorders: PCOS, Ovarian neoplasms

Lab: Testosterone, DHEA-S, 17α-hydroxyprogesteroneLab: Testosterone, DHEA-S, 17α-hydroxyprogesterone

Secondary Secondary Amenorrhea/Oligomenorrhea: Amenorrhea/Oligomenorrhea:

EvaluationEvaluation

HormoneLevelIndication

Testosterone< 200 ng/dLPCOS

> 200 ng/dLEvaluate for adrenal or ovarian tumor

DHEA-S< 700 ng/dLPCOS

> 700 ng/dLEvaluate for adrenal or ovarian tumor

17α-hydroxyprogesterone> 4 ng/mLConsider ACTH stimulation test to diagnose CAH

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 syndromeEPCT – negativeEPCT – 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 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

Amenorrhea/Oligomenorrhea: Amenorrhea/Oligomenorrhea: ManagementManagement

DiagnosisManagement

Ovarian insufficiencyPremature ovarian failure

Postmenopausal ovarian failure

Hormone replacement therapy (HRT)

*Congenital anatomic lesions Surgical correction

*Presence of Y chromosome (i.e. AIS)Gonadectomy

*Gonadal dysgenesis (i.e. Turner syndrome)Estrogen + progestin, growth hormoneIVF (IF pregnancy desired)

HyperprolactinemiaDopamine agonist (Bromocriptine, Cabergoline)

Functional hypothalamic amenorrhea Increase caloric intake < energy expenditure

Hypothalamic or pituitary dysfunction )non-reversible (

OCP’s, pulsatile GnRH or exogenous gonadotropins

CNS tumor Craniopharyngioma

Prolactinoma

Surgical resectionMicroadenoma (< 10mm) – Dopamine agonist

Macroadenoma (<10mm) – Trans-sphenoidal resection

PCOSOCP’s, weight loss, and metformin

Asherman’s syndromeHysteroscopic lysis of adhesions

Treatment goals of amennorrhea and oligomenorrhea include prevention of complications such as osteoporosis, endometrial hyperplasia and heart disease; preservation of fertility; and in primary amenorrhea, progression of normal pubertal development

Documents

SECONDARY AMENORRHEA Dr Hanaa Alani. AMENORRHEA Is the absence or abnormal cessation of the menses PHYSIOLOGIALAMENORRHEAPATHOLOGIALAMENORRHEA