AMENNORHEA

SALWA NEYAZICOSULTANT OBSTETRICIAN

GYNECOLOGISTPEDIATRIC & ADOLESCENT

GYNECOLOGIST

AMENORRHEA

WHAT IS 1RY AMENORRHEA? Lack of the onset of menses by the 16 Y in

a ♀ with 2ry sexual chct or by the age of 14 Y in ♀ without 2ry sexual development

WHAT IS 2RY AMENORRHEA? Cessation of menses for a period of 6

months in a ♀ who previously had initiation of menses

CLASSIFICATION OF 1RY AMENORRHEA

A-BREAST ABSENT UTERUS PRESENT GONADAL DYSGENESIS

1-TURNER SYNDROME 45XOVariations of Turner ‘s syndrome

2-Mosaicism XO/XX not always shortThey will have menses , get pregnant then develop premature menopause

3-Structural abnormalities of the X chromosome Deletion of the short arm of the X chromosome

Short stature Deletion of the long arm normal HT, 2ry

Amen, streak gonads

TURNER SYNDROME

FEATURES1ry amenorrhea No breast development Normal ♀♀ genital organs (external /internal)Streak gonads (ovaries are replaced by white nonfunctioning tissue)Short statureWebbed neck (Short broad neck) with a low hair lineCubitus vulgusShield chest / Widely spaced nipplesHigh arched palateShort 4th metacarpalCoarctation of the aorta or VSDHorse shoe kidney or single kidneyLymphedema

GONADAL DYSGENESIS

4-Pure gonadal dysgenesis 46XX Mutation in an autosomal gene

Accelerated germ cell loss Streak gonads

♀ genetalia , normal Mullerian structures

Rarely Turner’s Stigmata 5- Pure gonadal dysgenesis 46 XY ♀ genitalia

Streak gonads ↑ risk of malignancy

N Mullerian structures

GONADAL DYSGENESIS

6- 17-α hydroxylase deficiency (rare) ovarian synthesis of estrogens 1ry Amen

Sexual immaturity

cortisol ↑ ACTH

↑ Na K ↑ BP

↑ Progestrone as it is not converted to cortisol

7-Galactosaemia (rare) galactosaemia is toxic to oocytes

HYPOTHALAMIC FILURE8-Isolated GnRH deficiency (Kalman’s

Syndrome)

Anosmia & Hypogonadotropic Hypogonadism X linked ----Mutation in the KAL geneMore common in ♂ > ♀

Midline defects Cleft lip & Palate

Somatic defects color blindness, renal agenesis, retinitis pigmentosa, neurosensory

deafness

Lack 2ry sexual chct & the ability to smell

HT & bone age appropriate for age

HYPOTHALAMIC FILURE9-Hypogonadotropic Amenorrhea

CNS tumors GnRH pulses LH & FSH estradiolHypothalamic Lesions Craniopharyngioma

granuloma, aqueduct stenosis , & the sequelae of encephalitis CNS tr interfere with the –ve feedback of

Dopamine on Prolactin ↑ Prolactin Other causes of HypoGonadotropic Amen hypothyroidism

Prader Willi & Laurence Moon Biedl syndromes

HYPOTHALAMIC FILURE10-Anorexia Nervosa, Malnutrition,

Excessive Exercise & Chronic Illness

Functional GnRH deficiency May present with or without Breast developmentPhysical stress delay menarcheEach year of athelitic training before menarche delayed menarche 5 MOsteoporosis could occur with prolonged periods of Amenorrhea, low body Wt

B-BREAST PRESENT , UTERUS PRESENT

1-HYPOTHALAMIC CAUSES CNS lesions (tumors) Stress, Excessive exercise & low body Wt

2-PITUITARY CAUSES Hyperprolactinemia Hypothyroidism ↑ TRH ↑ prolactin

3-OVARIAN CAUSES PCO

4-OUTFLOW TRACT OBSTRUCTION Imperforate hymen Transverse vaginal septum

C-BREAST PRESENT , UTERUS ABSENT1-Testicular feminization/ Androgen

insensitivity

XY Karotype produce MIF Mullerian structures are absentComplete/ Partial absence of androgen receptorsX linked recessive or dominant Female external genitalia with Short blind vaginaTestosterone normal ♂ range

Breast development due to periferal conversion of androgens to estrogens

Sexual hair is absent due to absence of androgen receptors

Gonadectomy after puberty ↑ risk of malignancy (gonadoblastoma, dysgerminoma)

C-BREAST PRESENT , UTERUS ABSENT

2- 5 α reductase deficiency

Autosomal recessive Formation of the ♂ external genitalia requiers

5α REDUCTASE testosterone dihydrotestosterone

Formation of the internal wollfiane structures respond directly to testosterone

External genitalia ♀ with mild musculinizationAbsent uterusAt puberty testosterone secretion virilization

C-BREAST PRESENT , UTERUS ABSENT3-Mulerian Agenesis/ Mayer –Rokitansky-

Kuster-Huser syndrome

Etiology ?Failure of mullerian duct development absence of the upper vagina, cx & uterus (uterine reminants may be found)The ovaries & fallopian tubes are presentNormal 46XX ♀ with normal exrenal genitaliaPt present with 1ry amenorroea47% have asociared urinary tract anomalies12% skeletal anomaliesRx psychological counseling

surgical - vaginoplasty- vaginoplasty - excision of utrine reminant (if it

has fuctioning endometrium) -vaginal dilators

D-BREAST ABSENT, UTERUS ABSENT

The least common presentation of 1ry AmenAll Pt are 46 XYTestosterone or NFSH/LH ↑

A- 17-20 DESMOLASE DEFICIENCY The enzyme required for the synthesis of

Androgens Androgens estrogen The testes produce MIF therefore no Mullerian structures ♀ external genitalia Insufecient estrogens for breast development

D-BREAST ABSENT, UTERUS ABSENT

B- 17 α HYDROXYLASE DEFICIENCYSimilar to 17-20 desmolase defCortisol synthesis also ↑ BP,

hypernatraemia & hypokalaemia

C-AGONADISM

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

INVESTIGATIONS & TREATRMENT

Hx & Physical examination to place the Pt in one of the four

categories

CNS / HPDISORDER

Gonadal Dysgenesis

FSH ↑↑FSH

Karyotype

XY

Gonadectomy

XX

↑Na K↑Progestrone

17α hydroxylasedeficiency

XO

CT / MRIHEADCNS

TUMORS

↑TSH

ProlactinN

Wt ↑Exercise

Stress

1-BREAST ABSENT UTERUS PRESENT

TSHNPROLACTIN ↑ /N

Hypothyroidism

Kallman’sSyndrome

Wt ↑Exercise

Stress

Wt ↑Exercise

Stress

TREATMENT1-BREAST ABSENT UTERUS PRESENT

Gonadal Dysgenesis

XY

XX XO

Gonadectomy

Estrogen Progestrone

Replacement

Breast development / MensesImprove Bone Min Density

17αOH-DifCortisol

Kallman’sSyndrome

Estrogen Progestrone

Replacement

Wt ↑Exercise

Stress

PsychiatricHelp

Treat thecause

Hypothyroidism

Thyroxin

CNS Tmr

Treat accordingly

↑ProlactinTSHN

MRI/CTPituitary

Prolactin NTSH N

+Progestronechalange

Anovulatorycycle

-Progestrone chalange

FSH

Hypoth/ pituit Failure

↑FSHOvarianFailure

MRI/CTR/O

CNS TMR

Karyotyping

↑ TSHHypothyroid

2-BREAST PRESENT UTERUS PRESENT

Out flowTract

Obstruction

↑ TSHHypothyroid

↑ProlactinTSHN

↑ TSHHypothyroid

TREATMENT2-BREAST PRESENT UTERUS PRESENT

Hypoth/ pituit Failure

OvarianFailure

Out flowTract

Obstruction

↑ProlactinTSHN

↑ TSHHypothyroid Anovulatory

cycle

HRT

ProgestinD16-25

Bromocriptin

Surgery

Thyroxin

Testosterone N♀

3-BREAST PRESENT UTERUS ABSENT

↑Testosterone N♂

Karyotyping

XYTesticular

Feminization

Gonadectomy

Karyotyping

XXMullerian Agenesis

U/S PelvisU/S MRI Gonads

U/S PelvisU/S KIDNEY

IVP

3-BREAST PRESENT UTERUS ABSENT

XYTesticular

Feminization

XXMullerian Agenesis

Vaginoplasty

Vaginal dilatorsGonadectomy

HRT

4-BREAST ABSENT UTERUS ABSENT

All46 XY

Pysical ExamU/S

MRI forGonads

Gonadectomy HRT

2RY AMENORRHEA

2RY AMENORRHEA

WHAT IS 2RY AMENORRHEA?Cessation of menses for a period of 6 months or 3

consecutive menstrual cycles in a ♀ who previously had initiation of menses

WHAT IS THE PREVELANCE OF AMENORRHEA?

1.8-3%

WHAT IS THE CLASSIFICATON OF 2RY AMENORRHEA?

Hypergonadotropic

Hypogonadotrpic

Euogonadotrpic

Hperprolactinemia

Anatomic defects

CNS / HypothalamicPituitaryOvarianOutflow Uterine Cx Vaginal

HYPOGONADOTROPIC AMENORRHEA

“CNS / HYPOTHALAMIC ”Stress ↑ β-endorphins GnRH

FSH LH Estrogens

Exercise Excessive streneous exercise Runners & Ballet dancers

Mechanism Similar to stress Wt loss “Anorexia nervosa” More frequent in adolescent & young adults

0.5-1% of women aged 15 –30 years 15% < Ideal body Wt

Functional “Non of the above causes” No LH pulses or Persistant pulse frequency of “luteal phase ”

2ry to neurotransmitter abnormality of the CNS (? ↑ Opioid activity)

HYPOGONADOTROPIC AMENORRHEA

IS IT OF ANY CONCERN IF THESE YOUNG WOMEN BECOME AMENORRHEIC ?HYPOESTROGENISM is the main concern

WHY IS IT MORE WORRYING THAN THE MENOPAUSAL

WOMEN ?During adolescence estrogen plays a critical role in

determining PEAK BONE DENSITY which reached in the 2nd decade of life

HYPOGONADOTROPIC AMENORRHEA

IS THERE ANY EVIDENCE OF ITS EFFECT ON THE BONES?Amenorrheic Athletes Bone Mineral Density (BMD) in lumbar spines, femur, tibia Athletes with menstrual irregularities BMD <

athletes with regular cyclesAnorexia nervosa Pt BMD (0.64) < Normal controls (0.72)Anorexia nervosa Pt may have osteoporotic fractures

HYPOGONADOTROPIC AMENORRHEA

SHEHAN’S SYNDROMEPiuitary failure following sever post partum hemorrhageDeficiency of all pituitary hormonesFSH & LH Failure of ovarian follicular development

estrogen AmenorrheaRx HRT

hMG for ovulation induction

TREATMENT OF HYPOGONADOTROPIC

AMENORRHEA In training intensity to a level where regular menses resume HRT Cyclic estrogen / progestrone

Premarin 1.25 mg continuously Medroxyprogestrone acetate 5 mg /D for 12 D each cycle OCP better compliance

Anorexia nervosa Psychiatric Rx Meanwhile HRT Long term follow up Frequent relapses after

attaining ideal body WtFunctional HypoGt Amen HRT / ovulation induction

EUOGONADOTROPIC AMENORRHEA

PCOAmenorrhea / anovulatory cyclesEnlarged polycystic ovariesInfertilityHyperinsulinemia / ObesityHyperandrogenism / hirsutism↑ LH

Acyclic estrogen production / unopposed by progesrtrone ↑ risk of endometrial hyperplasia/Ca

Inheritable disorder with a complex inheritance pattern

TREATMENT OF PCO

AmenorrheaIrrigular cycles Hirsutism

Infertility

OCP OCPAnti

androgensCyclic

progest

-Protectendometrium

-Regulate cycle-menorrhagia

OvarianAndrogen↑SHBG

SprinolactoneCyproterone acetate

Flutamide

Bind androgen receptorsAndrogens

5αreductase activity

+

Clomid

hMG Ovariandrilling

Ovulation 70%Pregnancy 40%

Ovulation 92% Pregnancy 70%

HyperinsulinismObesity

Glucophage

Wt

Clomid

Ovulation 70%Pregnancy 40%

HYPERGONADOTROPIC AMENORRHEA

WHAT IS PREMATURE OVARIAN FAILURE (POF) ?2ry Amenorrhea ↑ FSH & LH

estrogen

Before the age of 40 Y

WHAT IS THE INCIDENCE OF POF ?

1%

WHAT IS THE CAUSE?

Unknown / autoimmune / genetic factors

Associated autoimmune disease 39%

POF

WHAT ARE THE PATHOLOGICAL CHCT OF POF ?TWO TYPES

Ovarian sclerosis & lack of folliclesResistant ovary syndrome

HOW TO MANAGE POF?R/O other autoimmune diseases RH factor

ANA, Antithyroid Antibodies, Antichromosomal Antibodies, glucose, cortisol, Ca , Ph, TSHHRT to prevent osteoprosisSpontaneous pregnancy can occur in women with

POF on HRT 8%hMG/HCG glucocorticoids have been cliamed to give

better pregnancy rates

HYPERPROLACTINEMIA

The most common pituitary cause of 2ry AmenorrheaCauses

-Pituitary adenoma -Idiopathic -Loss of inhibition by dopamine Hypothalamic or pituitary stalk lesions -Hypothyroidism -PCOS -Medications phenothiazines , haloperidol monoamineoxidase inhibitors, TCA, H2 receptors blockers

HYPERPROLACTINEMIA

Galactorrhea 1/3 of Pt Amenorrhea/ Hyperprolactinemia Pt at risk of

osteoporosis due to estrogenTREATMENT

- Hypothyroidism L-Thyroxin If still amenorrheic after RX Parlodel +

Thuroxin -If no substitute for the medications that

cause hyperprolactinemia HRT -Hypothalamic or pituitary stalk lesions Surgical excision

TREATMENT OF HYPERPROLACTINEMIA

PITUITARY ADENOMA (PROLACTINOMA) *Macroadenoma > 10 mm Respond to

medical Rx Dopamine agonist (bromocriptin) size of the tumor & prolactin level

Pt not responding to medical Rx or

not tolerating it Surgery/ Irradiation

*Microadenoma < 10mm remain stable in size Rx Bromocriptin prolactin level Normalize the menstrual

cycle

TREATMENT OF HYPERPROLACTINEMIA

IDIOPATHIC HYPERPROLACTINEMIA Rx Dopamine agonist Bromocriptin or

PergolideSide effects of dopamine agonists

-Postural hypotension -Nausea -Headache -Nasal stuffinessStarting with a low dose & gradually ↑ it helps to

avoid

The side effects

ANATOMICAL CAUSES

Uncommon cause of 2ry AmenorrheaAsherman’s Syndrome Hx of D/C for RPOC after abortion / puerperium or previous uterine infectionIntrauterine AdhesionsNormal hormones-ve progestrone chalange testDx HSG / HYSTROSCOPYRx Hystroscopic resection of the adhesions followed by estrogen therapy