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Amenorrhea Made Easy

By:

Mohammad EmamProf. OB & GYN

Mansoura Faculty of MedicineEGYPT

2015

Definition OfDefinition Of AmenorrheaAmenorrhea

• Is complete absence of Is complete absence of menstruation in the menstruation in the childbearing period.childbearing period.

Definition OfDefinition Of AmenorrheaAmenorrhea

Absence of menstruation.

Background• Understanding normal menstruation.

• Classification of amenorrhea.

• Amenorrhea is a Symptom not a disease, so the final diagnosis should be pathological .

Pre-requisities for normality of menstruation

• Coordinated Neuro endocrine Axis.Coordinated Neuro endocrine Axis.

• Responsive ,patent Utero vaginal canalResponsive ,patent Utero vaginal canal..

• Good general health .Good general health .

CONSTANT VARIABLE

Coordinated pituitary- ovarian –uterine Axis

Classifications Of Amenorrhea Classifications Of Amenorrhea • According to the onset:According to the onset:

– Primary amenorrhea.Primary amenorrhea.– Secondary amenorrhea.Secondary amenorrhea.

• According to the cause:According to the cause: – Physiological. Physiological. – Pathological Pathological

• According to Hidden or apparantAccording to Hidden or apparant:: – False amenorrhea False amenorrhea ((Crypto menorrheaCrypto menorrhea). ). – True amenorrhea.True amenorrhea.

• These are complementary to each otherThese are complementary to each other

Primary & Secondary

PrimaryPrimary Secondary Secondary

pubertal changespubertal changes -- Marshall & TannerMarshall & Tanner

Regular sequence of events between ages of 10-16 yrs in girlsRegular sequence of events between ages of 10-16 yrs in girls

GROWTH SPURT 8 - 14 yrs (9 yrs)6 - 10 cm / yr peak2.5 yrs duration

BREAST GROWTH (Thelarche) 8 - 13 yrs (11 yrs)

PUBIC HAIR (Pubarche) 9 - 13 yrs1st Pubertal Sign in 25%

AXILLARY HAIR (Adrenarche) 9.5 - 15 yrsmay follow menarche

MENSTRUATION (Menarche) 10 - 16 yrs (13 yrs)

Pathological:Pathological: Primary:Primary:

TrueTrue ( ( physiologic & pathologic)physiologic & pathologic)

FalseFalse

Secondary:Secondary:

TrueTrue( physiologic & pathologic)( physiologic & pathologic)

FalseFalse

Physiological.Physiological.•Before puberty. Before puberty. •After menarcheAfter menarche. . •During pregnancyDuring pregnancy..•During lactationDuring lactation . •During menopauseDuring menopause

According to causeAccording to cause

Hidden or true :

Crypto menorrhea =Obstruction of outflow tract below internal OS :Obstruction of outflow tract below internal OS :

• Primary: Primary: » Cervical atresia .Cervical atresia .» Vaginal aplasia. Vaginal aplasia. » Transverse vaginal septumTransverse vaginal septum» Imperforate hymenImperforate hymen

• Secondary:Secondary:» Cervical Cauterization. Cervical Cauterization. » Cervical conization ( Leep Cervical conization ( Leep

diathermy) diathermy) ..

» Vaginal synechiae Vaginal synechiae

Workup FOR DIAGNOSIS•Exclude physiologic causes

•Exclude anatomical.

•Clinical workup

Exclude physiologic causes

Exclude anatomical:

Cryptomenorrhea Ambiguous genitalia

Crypto menorrhea- Intermittent abdominal pain- Possible diff iculty with micturit ion- Possible lower abdominal swell ing- Bulging bluish membrane at the introitus or absent vagina (only dimple)

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Imperforate hymen

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False (crypto menorrhea)

hematometra

hematocolpos

Imperforate hymenHymenotomy or curiciate incision

Clinical workup Four phenotypes (Breast & uterus )

1. Absent breast + presence of uterus

2. Presence breast + absence uterus

3 Absence breast + absence uterus

4 . Presence breast + presence uterus

Breast is absent in cases with

Hypogonadism

Serum FSHSerum FSH

Absent breast + presence of uterus(Hypogonadism)

LOWLOW (less than 5 IU/l.)(less than 5 IU/l.) HIGH HIGH ((more than 20 IU/lmore than 20 IU/l))

GnRH challengeGnRH challenge ..

LOW FSHLOW FSH HIGH FSHHIGH FSH

PITUITARYPITUITARY HYPOTHALAMICHYPOTHALAMIC

History , exam & investigationHistory , exam & investigation

PRIMARY OV. FAILUREPRIMARY OV. FAILURE

Gonadal dysgenesisGonadal dysgenesisKARYOTYPEKARYOTYPEGonadal biopsyGonadal biopsy

Hypothalamo - pituitary

Gonadal dysgenesis (Turner’s syndrome)•• Sexual infanti l ism and short stature.Sexual infanti l ism and short stature.• • Associated abnormalit ies:Associated abnormalit ies:

– webbed neck,webbed neck,– cubitus valguscubitus valgus– coarctation of the aorta,coarctation of the aorta,– high-arched palate,high-arched palate,– broad shield-like chest with widely spaced nipples, broad shield-like chest with widely spaced nipples, – short metacarpal bonesshort metacarpal bones– Renal anomalies.Renal anomalies.

• • Bilateral streaked gonads.Bilateral streaked gonads.• • Karyotype - 80 % 45, X0 Karyotype - 80 % 45, X0 - - 20% mosaic forms (46XX/45X0)20% mosaic forms (46XX/45X0)

• • TreatmentTreatment : HRT : HRT

Gonadal Dysgenesis (Turner’s syndrome)

Mosaic (46-XX / 45-XO) (Classic 45-XO)

Turner’s syndrome

Causes of hypothalmo - pituitary

• CongenitalCongenital

• TraumaticTraumatic

• InflammatoryInflammatory

• NeoplasticNeoplastic

• MiscellaneousMiscellaneous

Hypothalamus & Pituitary (Hypogonadotropic )Hypogonadotropic )

• HypothalamusHypothalamus : :• StressStress• Weight changes :anorexia nervosa ,bulimiaWeight changes :anorexia nervosa ,bulimia• Exercise Exercise • Psuedocyesis Psuedocyesis ( ?!!!) Thanks for sonar( ?!!!) Thanks for sonar• SyndromesSyndromes

• Pituitary :Pituitary :• Craniopharyngioma.Craniopharyngioma.• Adenomas.Adenomas.• syndromessyndromes . e.g. Sheehan's syndrome . e.g. Sheehan's syndrome

Emotional stress

• Emotional Emotional shockshock

• Stress Stress Endorphins Endorphins

Gn RGn Rh h

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Weight changes

• Weight lossWeight loss ( (15% of ideal wt for 15% of ideal wt for

age)age) whether By:whether By:• Diet regimen Diet regimen • Anorexia nervosaAnorexia nervosa

• Excess weight gain :Excess weight gain :• simple overeating simple overeating

• Bulimia nervosaBulimia nervosa. .

Kallmann Syndrome

• Deficient secretion of GnRH Deficient secretion of GnRH ++ anosmia.anosmia.

• Possible co-existing featuresPossible co-existing features include: include: • Bone anomalies. Bone anomalies. • Renal anomalies. Renal anomalies. • Cleft lip and palate.Cleft lip and palate.

• Color blindness.Color blindness. ..

Frolich syndrome

–Primary amenorrhea.Primary amenorrhea.–Hypogonadism.Hypogonadism.–Trunkal obesity.Trunkal obesity.

Laurence-Moon -Biedle syndrome

• As As FrolichFrolich syndrome with: syndrome with: – Polydactyl.Polydactyl.– Syndactly.Syndactly.– Mental retardation. Mental retardation. – Retinitis pigmentosaRetinitis pigmentosa..

Craniopharyngioma

• Arises from remnants of Arises from remnants of Rathke's Rathke's pouchpouch • Compresses the hypothalamusCompresses the hypothalamus

• Suppress Suppress GnRHGnRH secretion . secretion .

• Interrupt portal flow of Interrupt portal flow of GnRH GnRH in the pituitary stalk.in the pituitary stalk.

• Calcifications may be apparent on radiography of Calcifications may be apparent on radiography of the the sella turcica.sella turcica.

• Frequent manifestations include Frequent manifestations include visual field defects visual field defects

and blurring visionand blurring vision..

GalactorrhoeaGalactorrhoea + + amenorrhea.amenorrhea.

• Chiari-Frommel syndrome –It occurs It occurs after deliveryafter delivery: due to : due to

persistent persistent ProlactinProlactin secretion. secretion.

• Delcastello syndrome:• It is not preceded by delivery.It is not preceded by delivery.

Levi- Lorian Syndrome (Pituitary infantilism)

–Amenorrhea.Amenorrhea.

–Hypogonadism.Hypogonadism.

–Short stature (Dwarfism).Short stature (Dwarfism).

Sheehan's syndrome &Simmonds

• Postpartum hge.Postpartum hge.

• Failure of gonadotrphic function + Failure of gonadotrphic function + failure of failure of lactationlactation..

• More extensive damage lead to :More extensive damage lead to :

• Simmonds :Simmonds : (Destruction of the anterior pituitary gland (Destruction of the anterior pituitary gland due to due to septic emboliseptic emboli due to due to puerperal sepsispuerperal sepsis.).)

Pituitary Adenoma• Evaluation of the Evaluation of the sella turcicasella turcica with with (MRI) (MRI) + + radiographyradiography is is

necessary.necessary. • Vary in size.Vary in size.

• Micro adenomasMicro adenomas (less than 10 mm). (less than 10 mm).

• Macro adenomasMacro adenomas (more than 10 mm).(more than 10 mm).

• May be May be associatedassociated with: with: – Visual changes. Visual changes. – Galactorrhoea.Galactorrhoea.– Hypothyroidism.Hypothyroidism.– AmenorrheaAmenorrhea

Work up for : hypothalamic- pituitary

• History • Exam• Investigation…

• Then:• Categorize as primary or secondary

• Categorize cause……..

History in primary amenorrhea

• Developmental milestones (age of growth spurt ,age of thelarche, adrenarche)

• Chronic illness (CRI ,TB, Bl disease).

• Weight changes

• Excessive exercise

• History of anosmia

Examination

• General condition

• Height

• BMI

• 2ndary sex characters

Investigations• Bed –side:

• Visual field in suspected pituitary adenoma• Laboratory:

• BHCG: to exclude pregnancy• Serum prolactin• TSH

• Imaging:– Ultrasound : prove presence or absence of uterus, measure its size– CT– MRI

• Instrumental:– Hysteroscopy: uterine synechia– Laparoscopy

Sexual hair & Karyotype

46-XX

Mullerian Agenesis

(MRKH syndrome)

Andogen Insenitivity

(TSF syndrome)

46-XY

Presence of sexual hair

Absent sexualhair

2. Presence breast + absence uterus

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Utero-vaginal Agenisis Mayer- Rokitansky- Kuster-Hauser syndrome

• Normal breasts.Normal breasts.• N. sexual hair development .N. sexual hair development .• Normal looking external female genitaliaNormal looking external female genitalia• Normal female range testosterone levelNormal female range testosterone level• Absent uterus and upper vagina Absent uterus and upper vagina • Normal ovariesNormal ovaries• Karyotype 46-XXKaryotype 46-XX• 15-30% renal, skeletal and middle ear 15-30% renal, skeletal and middle ear

anomalies.anomalies.

• Treatment :Treatment :

STERILE? Vaginal creation : Dilatation & STERILE? Vaginal creation : Dilatation & VaginoplastyVaginoplasty))

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Testicular feminization syndrome

• Normal breasts but no sexual hairNormal breasts but no sexual hair• Normal looking female external Normal looking female external

genitaliagenitalia• Absent uterus and upper vaginaAbsent uterus and upper vagina• Karyotype 46, XYKaryotype 46, XY• MaleMale range testosterone level range testosterone level

• Treatment Treatment ::– gonadectomy after puberty + HRTgonadectomy after puberty + HRT– ? Vaginal creation ? Vaginal creation (Vaginoplasty )(Vaginoplasty )

Vaginal Agenesis: Comparison of Two Syndromes

Mullerian AgenesisMullerian Agenesis Androgen Androgen Insensitivity Insensitivity Syndrome Syndrome

VaginaVagina absentabsent absentabsent

Pubic hairPubic hair presentpresent absentabsent

BreastsBreasts presentpresent PresentPresent

GonadsGonads ovariesovaries TestesTestes

UterusUterus absentabsent AbsentAbsent

Testestrone levelTestestrone level Female levelFemale level Male levelMale level

KaryotypeKaryotype 46 XX46 XX 46 XY46 XY

3. absence breast + absence uterus

•17, 20 desmolase deficiency

•17 a hydroxylase deficiency•Agonadism

Very rareall are 46 Xy

AGONADISM

•Degeneration of the testes (in utero) after the production of the MIF

PREGESTERONEPREGESTERONE

BLEEDINGBLEEDING NO BLEEDINGNO BLEEDING

CHRONIC ANOVULATIONe.g PCOS

COMBINED OESTROGENCOMBINED OESTROGEN & PROGESTERONE& PROGESTERONE

BLEEDINGBLEEDING NO BLEEDINGNO BLEEDING

OVARIAN FAILURE( Non dysgenetic)

SERUM FSHSERUM FSH

UTERINE FACTOR( Ashermann syndrome)

4. Presence breast + presence uterus (Like secondary amenorrhea)

Summary of Sub-phenotypes Amenorrhea

Breast Breast – – aBsentaBsent

UterUs absent

UterUs Present

17, 20 desmolase deficiency

1. Gonadal failure turner 45X

17 a hydroxylase deficiency 46xy

Gonadal dysgenisis

Agonadism 17 a hydroxylase deficiency with 46XX

2. Hypothalamic failure

3. Pituitary failure

Breast Breast – – PresenPresentt

AIS (T.F.) Hypothalamic, pituitary, ovarian & uterine etiology

Mullerian agenesis

General Principles of management

• Try causative Treatment.

• Do not forget general factors

• Remember stress is common cause in adolescents

• Pregnancy is the commonest cause of secondary amenorrhea

General Principles of management

. HRT: (estrogen and progesterone)

In hypo-estrogenic amenorrheic women (to prevent

osteoporosis)

. Periodic progestogen:In euestrogenic amenorrheic women (to avoid endometrial cancer)

. If Y chromosome is present: gonadectomy is indicated

. Many cases require frequent re-evaluation

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