AMENNORHEA

SALWA NEYAZI
COSULTANT OBSTETRICIAN
GYNECOLOGIST
PEDIATRIC & 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 45XO
Variations of Turner s syndrome
2-Mosaicism XO/XX not always short
They 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
FEATURES
1ry amenorrhea
No breast development
Normal genital organs (external /internal)
Streak gonads (ovaries are replaced by white
nonfunctioning tissue)
Short stature
Webbed neck (Short broad neck) with a low hair
line
Cubitus vulgus
Shield chest / Widely spaced nipples
High arched palate
Short 4th metacarpal
Coarctation of the aorta or VSD
Horse shoe kidney or single kidney

GONADAL DYSGENESIS
4-Pure gonadal dysgenesis 46XX
Mutation in an autosomal gene
Accelerated germ cell loss Streak
gonads
genetalia , normal Mullerian structures
Rarely Turners Stigmata
5- Pure gonadal dysgenesis 46 XY
genitalia
Streak gonads risk of malignancy
N Mullerian structures

GONADAL DYSGENESIS
6- 17- 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 FILURE
8-Isolated GnRH deficiency (Kalmans
Syndrome)
Anosmia & Hypogonadotropic Hypogonadism
X linked ----Mutation in the KAL gene
More 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 FILURE
9-Hypogonadotropic Amenorrhea
CNS tumors GnRH pulses LH & FSH
estradiol
Hypothalamic 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 FILURE
10-Anorexia Nervosa, Malnutrition,
Excessive Exercise & Chronic Illness
Functional GnRH deficiency
May present with or without Breast
development
Physical stress delay menarche
Each year of athelitic training before
menarche delayed menarche 5 M
Osteoporosis 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 ABSENT

1-Testicular feminization/ Androgen
insensitivity
XY Karotype produce MIF Mullerian structures are
absent
Complete/ Partial absence of androgen receptors
X linked recessive or dominant
Female external genitalia with Short blind vagina
Testosterone 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 reductase deficiency
Autosomal recessive
Formation of the external genitalia requiers
5 REDUCTASE
testosterone dihydrotestosterone
Formation of the internal wollfiane structures
respond directly to testosterone
External genitalia with mild musculinization
Absent uterus
At puberty testosterone secretion virilization

C-BREAST PRESENT , UTERUS ABSENT

3-Mulerian Agenesis/ Mayer RokitanskyKuster-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 present
Normal 46XX with normal exrenal genitalia
Pt present with 1ry amenorroea
47% have asociared urinary tract anomalies
12% skeletal anomalies
Rx psychological counseling
surgical - vaginoplasty
- excision of utrine reminant (if it has
fuctioning endometrium)
-vaginal dilators

D-BREAST ABSENT, UTERUS

ABSENT
The least common presentation of 1ry Amen
All Pt are 46 XY
Testosterone or N
FSH/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 HYDROXYLASE DEFICIENCY
Similar to 17-20 desmolase def
Cortisol 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

BREAST ABSENT UTERUS PRESENT-1

FSH

FSH
Kallmans
Syndrome
Wt
Wt
Exercise
Exercise
Stress
Stress

CNS / HP
DISORDER

17 hydroxylase
deficiency

Gonadal
Dysgenesis

Na K
Progestrone

TSH
ProlactinN

TSHN
PROLACTIN /N

XX
Karyotype

Hypothyroidism

CNS
TUMORS

CT / MRI
HEAD
XO

XY
Gonadectomy

TREATMENT
BREAST ABSENT UTERUS PRESENT-1
Hypothyroidism

Thyroxin

Gonadal Dysgenesis

Wt
Exercise
Stress

17OH-Dif
Cortisol

XX

XO
XY

CNS Tmr
Psychiatric
Help
Treat thecause

Kallmans
Syndrome

Gonadectomy

Treat
accordingly
Estrogen
Progestrone
Replacement

Estrogen
Progestrone
Replacement

Breast development / Menses

Improve Bone Min Density

BREAST PRESENT UTERUS PRESENT-2

TSH
TSH
Hypothyroid
Hypothyroid

Prolactin
Prolactin
TSHN
TSHN

Karyotyping

FSH

Prolactin N
TSH N

Ovarian
Failure

Progestron
e
chalange
Out flow
Tract
Obstruction
MRI/CT
R/O
CNS TMR

MRI/CT
Pituitary

FSH

Progestrone+
chalange

Hypoth/ pituit
Failure

Anovulatory
cycle

TREATMENT
BREAST PRESENT UTERUS PRESENT-2
TSH
Hypothyroid

Out flow
Tract
Obstruction

Prolactin
TSHN

Anovulatory
cycle

Ovarian
Failure

Hypoth/ pituit
Failure

Thyroxin
Bromocriptin

Surgery

HRT

Progestin
D16-25

BREAST PRESENT UTERUS ABSENT-3

Testosterone N

Karyotyping

XY
Testicular
Feminization

Testosterone N

Karyotyping

XX
Mullerian Agenesis

Gonadectomy
U/S Pelvis
U/S MRI
Gonads

U/S Pelvis
U/S KIDNEY
IVP

BREAST PRESENT UTERUS ABSENT-3

XX

XY
Testicular
Feminization

Mullerian Agenesis

HRT

Vaginoplasty

Gonadectomy
Vaginal dilators

BREAST ABSENT UTERUS ABSENT-4

All
XY 46

Pysical Exam
U/S
MRI for
Gonads

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
CNS / Hypothalamic
Hypogonadotrpic
Pituitary
Euogonadotrpic
Ovarian
Hperprolactinemia
Outflow Uterine Cx
Anatomic defects
Vaginal

HYPOGONADOTROPIC
AMENORRHEA
CNS / HYPOTHALAMIC
Stress -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 cycles
Anorexia nervosa Pt BMD (0.64) < Normal
controls (0.72)
Anorexia nervosa Pt may have osteoporotic
fractures

HYPOGONADOTROPIC
AMENORRHEA
SHEHANS SYNDROME
Piuitary failure following sever post partum
hemorrhage
Deficiency of all pituitary hormones
FSH & LH Failure of ovarian follicular
development
estrogen Amenorrhea
Rx 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 Wt
Functional HypoGt Amen HRT / ovulation
induction

EUOGONADOTROPIC
AMENORRHEA
PCO
Amenorrhea / anovulatory cycles
Enlarged polycystic ovaries
Infertility
Hyperinsulinemia / Obesity
Hyperandrogenism / hirsutism
LH
Acyclic estrogen production / unopposed by
progesrtrone risk of endometrial hyperplasia/Ca
Inheritable disorder with a complex inheritance pattern

TREATMENT OF PCO
Infertility
Amenorrhea
Irrigular cycles

Hirsutism

Hyperinsulinism
Obesity
Clomid
Gluco
phage

Cyclic
progest

OCP

-Protect
endometrium
Regulate cyclemenorrhagia-

OCP

Wt

hMG

Anti
+ androgens

Ovarian
Androgen
SHBG

Sprinolactone
Cyproterone acetate
Flutamide
Bind androgen receptors
Androgens
5reductase activity

Ovarian
drilling

Ovulation 70%
Pregnancy 40%
Ovulation 92%
Pregnancy 70%

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 follicles
Resistant ovary syndrome
HOW TO MANAGE POF?
R/O other autoimmune diseases RH factor
ANA, Antithyroid Antibodies, Antichromosomal
Antibodies, glucose, cortisol, Ca , Ph, TSH
HRT to prevent osteoprosis
Spontaneous 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
Amenorrhea
Causes
-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 estrogen
TREATMENT
- 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
Pergolide
Side effects of dopamine agonists
-Postural hypotension
-Nausea
-Headache
-Nasal stuffiness
Starting with a low dose & gradually it helps to
avoid
The side effects

ANATOMICAL CAUSES
Uncommon cause of 2ry Amenorrhea
Ashermans Syndrome Hx of D/C for RPOC
after abortion / puerperium or previous uterine
infection
Intrauterine Adhesions
Normal hormones
-ve progestrone chalange test
Dx HSG / HYSTROSCOPY
Rx Hystroscopic resection of the adhesions
followed by estrogen therapy