ASSESSMENT OF A CASE OF ASSESSMENT OF A CASE OF AMENORRHEAAMENORRHEA

Prof. Ashis Kumar MukhopadhyayProf. Ashis Kumar MukhopadhyayProfessor, G & OProfessor, G & O

Medical Superintendent-cum-Vice PrincipalMedical Superintendent-cum-Vice PrincipalCSS College of Obstetrics & Gynaecology, KolkataCSS College of Obstetrics & Gynaecology, Kolkata

National Chairperson, Medical Education Committee of FOGSINational Chairperson, Medical Education Committee of FOGSI

AMENORRHEAAMENORRHEA

Amenorrhea is the absence or abnormal cessation of the Amenorrhea is the absence or abnormal cessation of the menses. A patient is diagnosed with menses. A patient is diagnosed with primary amenorrhea primary amenorrhea if if she has not reached menarche by age 14 without the she has not reached menarche by age 14 without the appearance of secondary sex characterististics and by the age appearance of secondary sex characterististics and by the age 16 with secondary sex characteristics. 16 with secondary sex characteristics.

She meets the criteria for She meets the criteria for secondary amenorrhea secondary amenorrhea if if established menses have ceased for longer than 6 months or established menses have ceased for longer than 6 months or at least 3 of the previous cycle intervals. at least 3 of the previous cycle intervals.

TypesTypes

PhysiologicalPhysiological PathologicalPathological

PrimaryPrimary

----Before Before pubertypuberty

SecondarySecondary

pregnancypregnancy

LactationLactation

MenopauseMenopause

Concealed Concealed (Cryptomenorrhoea)(Cryptomenorrhoea)

CongenitalCongenital AcquiredAcquired

Real (True)Real (True)

PrimaryPrimary SecondarySecondary

Five basic factors for normal menstruationFive basic factors for normal menstruation

Normal female chromosome 46 XXNormal female chromosome 46 XX Co-ordination of H-P-O axisCo-ordination of H-P-O axis Responsive EndometriumResponsive Endometrium Patent outflow tractPatent outflow tract Ancillary glands like Thyroid and AdrenalAncillary glands like Thyroid and Adrenal

CausesDisorders of H-P-O axisDisorders of H-P-O axisHypogonadotropic HypogonadismHypogonadotropic Hypogonadism

Constitutional delayed pubertyConstitutional delayed puberty

Kallman’s syndromeKallman’s syndrome

CNS tomours like craniopharyngiomaCNS tomours like craniopharyngioma

Isolated FSH deficiencyIsolated FSH deficiency

Hypergonadotropic HypogonadismHypergonadotropic Hypogonadism

Primary Ovarian FailurePrimary Ovarian Failure

17-alpha Hydroxylase deficiency17-alpha Hydroxylase deficiency

Gonadal dysgenesisGonadal dysgenesis

Causes Abnormal chromosomal patternAbnormal chromosomal pattern

Turner’s syndrome (45XO)Turner’s syndrome (45XO) Mosaicism 45 X/ 46 XXMosaicism 45 X/ 46 XX Pure Gonadal dysgenesis (46 XX or 46 XY)Pure Gonadal dysgenesis (46 XX or 46 XY) Androgen Insensitivity SyndromeAndrogen Insensitivity Syndrome Partial deletion of X chromosome:-Partial deletion of X chromosome:-

Deletion of long arm (Xq-) Deletion of long arm (Xq-) Streak Gonads but no somatic Streak Gonads but no somatic abnormalities abnormalities

Deletion of short arm (Xp-)Deletion of short arm (Xp-) Somatic features like Turner’s Somatic features like Turner’s

CausesDevelopmental defect of Genital tractDevelopmental defect of Genital tract

Imperforate HymenImperforate Hymen Transverse Vaginal SeptumTransverse Vaginal Septum Atresia of upper 1/3Atresia of upper 1/3rdrd. Of vagina. Of vagina Complete absence of vaginaComplete absence of vagina Absent UterusAbsent Uterus

Dysfunction of Thyroid and Adrenal CortexDysfunction of Thyroid and Adrenal Cortex Adrenogenital syndromeAdrenogenital syndrome CretinismCretinism

CausesMetabolic disorders

Juvenile DMSystemic illness

MalnutritionAnaemiaWt. LossTuberculosis

Unresponsive EndometriumCongenitalSynaechiae (rare)

Etiology of AmenorrheaEtiology of AmenorrheaPrimaryPrimary    

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%)

SecondarySecondary     Chronic anovulation (39%)Chronic anovulation (39%)   Hypothyroidism / hyperprolactinemia(20%) Hypothyroidism / hyperprolactinemia(20%)  Weight loss/anorexia(16%)Weight loss/anorexia(16%)

THE ASSESSMENTTHE ASSESSMENT

Primary amenorrhea

abnormal ovariesabnormal ovaries abnormal hormonal stimulation abnormal hormonal stimulation of normal ovariesof normal ovaries

Chromosome Chromosome AnalysisAnalysis

breasts have breasts have developeddeveloped

FSH LevelFSH Level

no

high low

EstrogenizedEstrogenized

the (MPA) challengethe (MPA) challenge

+ -

vagina

no yes

congenital uterovaginal congenital uterovaginal agenesis imperforate agenesis imperforate hymen complete hymen complete transverse vaginal transverse vaginal septumseptum

Pubic hairnoyes

complete androgen complete androgen insensitivity insensitivity syndrome (CAIS)syndrome (CAIS)

Secondary Amenorrhea Secondary Amenorrhea

Incidence

1% of women of of women of reproductive age.reproductive age.

The most common cause of secondary amenorrhea The most common cause of secondary amenorrhea

in reproductive age women isin reproductive age women is pregnancy and this and this

should always be excluded by physical exam and should always be excluded by physical exam and

laboratory testing for the pregnancy hormone - laboratory testing for the pregnancy hormone -

HCG. 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.

GalactorrhoeaGalactorrhoeaHot flashes, breast atrophy and decreased libidoHot flashes, breast atrophy and decreased libidoCertain medicationsCertain medicationsA large amount of weight loss or gain A large amount of weight loss or gain Anorexia nervosaAnorexia nervosaCushing's disease and hypothyroidismCushing's disease and hypothyroidism Sheehan's syndrome.Sheehan's syndrome.Asherman's syndromeAsherman's syndromeAmenorrhoea following cervical conizationAmenorrhoea following cervical conizationFollowing discontinuation of oral contraception Following discontinuation of oral contraception

HistoryHistory

Psychological dysfunction or emotional stressPsychological dysfunction or emotional stressFamily history of apparent genetic anomaliesFamily history of apparent genetic anomalies

Physical examinationPhysical examination Height, Weight and nutritionHeight, Weight and nutrition Growth and developmentGrowth and development Signs of androgen excessSigns of androgen excess Endocrinal stigmaEndocrinal stigma The breast exam may reveal galactorrhoea The breast exam may reveal galactorrhoea Estrogen deficiency may be suggested on pelvic exam by a Estrogen deficiency may be suggested on pelvic exam by a

smooth vagina that lacks the normal rugae (wrinkles) and a smooth vagina that lacks the normal rugae (wrinkles) and a dry endocervix with no mucous.dry endocervix with no mucous.

Size of pelvic organs.Size of pelvic organs.

What we will do next?

If the history and physical exam are If the history and physical exam are suggestive of a certain etiology :suggestive of a certain etiology :

for the sake of efficiency and cost-effectiveness, the workup can sometimes be more directed.

( in 85% of cases .)

Some patients will not demonstrate any obvious Some patients will not demonstrate any obvious etiology for their amenorrhea on history and etiology for their amenorrhea on history and physical exam. These patients can be worked physical exam. These patients can be worked

up in a logical manner using a stepwise up in a logical manner using a stepwise approach. approach.

The first tests to perform after The first tests to perform after pregnancy is ruled out are :pregnancy is ruled out are :

a progesterone withdrawal test a progesterone withdrawal test

TSH (thyroid stimulating hormone) TSH (thyroid stimulating hormone)

prolactin level. prolactin level.

FSH>30-40FSH>30-402wk2wk

repeatrepeat

PROFPROF

hypoestrogenic hypoestrogenic

+ve.est,progest.c+ve.est,progest.challenge testhallenge test

FSH norm.FSH norm.

Repeat+serum ,est.levelRepeat+serum ,est.level

hypothalamic-pituitary hypothalamic-pituitary failure failure

-VE Preg.test-VE Preg.test

TSH ,PROLACTIN’, TSH ,PROLACTIN’, Prog.challenge testProg.challenge test

withdrawal withdrawal bleeding bleeding

anovulationanovulation

without withdrawal without withdrawal bleeding bleeding

compromised compromised outflow tract. outflow tract.

-ve.est, -ve.est, progest. progest. challenge testchallenge test

Normal FSHNormal FSH

HSG OR hysteroscopyHSG OR hysteroscopy ashermanasherman

-VE Preg.test-VE Preg.test

TSH ,PROLACTIN’, TSH ,PROLACTIN’, Prog.challenge testProg.challenge test

withdrawal withdrawal bleeding bleeding

without withdrawal without withdrawal bleeding bleeding

hypoestrogenic hypoestrogenic compromised compromised outflow tract. outflow tract. +ve.est,progest.c+ve.est,progest.c

hallenge testhallenge test -ve.est,progest-ve.est,progest.challenge test.challenge test

FSH>30-40FSH>30-40Normal FSHNormal FSH

HSG OR hysteroscopyHSG OR hysteroscopy ashermanasherman

2wk2wk

FSH norm.FSH norm.

repeatrepeatRepeat+serum ,est.levelRepeat+serum ,est.level

PROFPROFhypothalamic-pituitary hypothalamic-pituitary failure failure

anovulationanovulation

Ovarian failure (premature menopause)Ovarian failure (premature menopause)

chromosomal chromosomal anomalies anomalies

If the woman is under 30, a If the woman is under 30, a karyotype should be performed karyotype should be performed to rule out any mosaicism to rule out any mosaicism involving a Y chromosome.involving a Y chromosome.

If a Y chromosome is found If a Y chromosome is found the gonads should be the gonads should be surgically excised. surgically excised.

autoimmune autoimmune disease disease

it is prudent to screen for thyroid, parathyroid, and adrenal dysfunction

Laboratory evidence of autoimmune phenomenon is much more prevalent than clinically significant disease

Autoimmune Related Dysfunction Autoimmune Related Dysfunction

The most common association is with thyroid disease, The most common association is with thyroid disease, but the parathyroids and adrenals can also be affected. but the parathyroids and adrenals can also be affected.

Several studies have shown laboratory evidence of Several studies have shown laboratory evidence of immune problems in about 15-40% of women with immune problems in about 15-40% of women with premature ovarian failure. premature ovarian failure.

In general, ovarian biopsy is not indicated in patients In general, ovarian biopsy is not indicated in patients with premature ovarian failure since no clinically useful with premature ovarian failure since no clinically useful information will be obtained. information will be obtained.

Hypothalamic-pituitary failure

Patients who do not bleed after the progestin Patients who do not bleed after the progestin challenge but do after estrogen/progestin and have challenge but do after estrogen/progestin and have normal or low FSH and LH levels normal or low FSH and LH levels

Hypothalamic-pituitary failure Some medications (e.g. phenothiazines) as well as

extremes of weight loss, stress or exercise can cause this type of secondary amenorrhea.

A pituitary or hypothalamic tumor would be a rare finding in these patients who were all screened with prolactin levels at the beginning of the diagnostic evaluation.

However, if there is no cause apparent from the history, it would be prudent to obtain a baseline CT (or MRI) evaluation of the sellar region to rule out a space occupying lesion.

Hypothalamic-pituitary failure Patients with normal prolactin levels and normal Patients with normal prolactin levels and normal

imaging studies have hypothalamic amenorrhea of imaging studies have hypothalamic amenorrhea of uncertain etiology.uncertain etiology.

If the amenorrhea and lack of withdrawal bleeding If the amenorrhea and lack of withdrawal bleeding persists, prolactin levels should be measured persists, prolactin levels should be measured annually since a small microadenoma could be annually since a small microadenoma could be present that is escaping laboratory and radiographic present that is escaping laboratory and radiographic detection.detection.

Hypothalamic-pituitary failure

In this condition, as well as in the other hypothalamic In this condition, as well as in the other hypothalamic amenorrhea situations, the patients can be significantly amenorrhea situations, the patients can be significantly hypo estrogenic (a low estrogen situation similar to hypo estrogenic (a low estrogen situation similar to menopause). If the state is persistent, hormone menopause). If the state is persistent, hormone replacement therapy should be considered for protection replacement therapy should be considered for protection against osteoporosis. One approach is to get an estradiol against osteoporosis. One approach is to get an estradiol level and level and if it is less than 30 pg/ml, counsel the patient counsel the patient that hormonal replacement therapy is indicated that hormonal replacement therapy is indicated