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Amenorrhea
Criseline D. Tolentino, MD, DPOGS, FPSSTD

Step 1

TSH, Prolactin
Prog challenge

TSH

Hypothyroidism

PRIMARY AMENORRHEA

Absence of menses (IN WOMEN) by 16 years of age in the presence of

normal secondary sexual characteristics.
Absence of menses (IN WOMEN) by 14 years of age when there is no visible
secondary sexual characteristics.

SECONDARY AMENORRHEA

Absence of menstruation for three normal menstrual cycles of six months

after menarche.

COMPARTMENTAL SYSTEMS

Compartment Idisorders of the outflow tract

Compartment IIdisorders of the ovary
Compartment IIIdisorders of the anterior pituitary
Compartment IVdisorders of the CNS (hypothalamic factors)

DIAGNOSTIC EVALUATION
History and PE:
Evidence of psychological dysfunction or emotional stress
Family hx of apparent genetic anomalies
Nutritional status
Abnormal G&D
Presence of a normal reproductive tract
Evidence of CNS disease
-

Genital examination: blind or absent vagina with breast development:

mullerian agenesis, transverse vaginal septum or AIS
UTZ: useful to confirm the presence of uterus

+withdrawal
challenge

N prolactin
N TSH

anovulation

Step 2
No withdrawal bleeding
The target organ outflow tract is inoperative or preliminary estrogen
proliferation of the endometrium has not occurred
Treatment: estrogen 2.25mg CEE or 2mg EE ODx21 days + progesterone
10mg OD for the last 5 days (necessary to achieve withdrawal)
If still without withdrawal: end organ problem
Step 3
Designed to determined whether the lack of estrogen is due to a fault in the
follicle (compartment II) or in the CNS (compartment II & IV)
Normal adult female FSH and LH: 5-20 IU/L with the ovulatory midcycle
peak about 2x the base level
Suggested diagram aiding in the evaluation of women with amenorrhea
1. History and PE
FSH (-)
2. R/O pregnancy
Autoimmune defect
3. FSH & PRL
(Mullerian dysgenesis)
FSH, or (-)
Chronic anovulation
(PCD) Functional
Hypothalamic amenorrhea
PRL
Radiographic evaluation (Prolactinoma)
FSH
Gonadal failure (Gonadal dysgenesis?)

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II.

Common causes of primary amenorrhea

Category
Breast development
Mullerian agenesus
Androgen insensitivity
Vaginal septum
Imperforate hymen
Constitutional delay
No breast development: high FSH
46 XX
46 XY
No breast development: low FSH
Constitutional delay
Prolactinomas
Kallman syndrome
Other CNS
Stress, weight loss, anorexia
PCOS
Congenital adrenal hyperplasia
Others

Approximate
frequency (%)
30
10
9
2
1
8
40
15
5
30
10
5
2
3
3
3
3
1

Classification of amenorrhea

Primary Hypogonadism
A. Gonadal karyotype
1. Abnormal karyotype
Turner syndrome 45,X
mosaicism
2. normal karyotype
pure gonadal dysgenesis
i. 46, XX
ii. 46, XY (Swyer syndrome)
B. gonadal digenesis
C. enzymatic deficiency
1. 17a-hydroxylase deficiency
2. 17, 20-lyase deficiency
3. Aromatase deficiency
D. Premature ovarian failure
1. Idiopathic
2. Injury
Chemotherapy
Radiation
Mumps
Oophoritis
3. Resistant ovary (idiopathic)

(Not including disorders of congenital sexual ambiguity)

I.

Anatomic Defects (outflow tract)

A. Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome)
B. Complete androgen resistance (testicular feminization)
C. Intrauterine synechiae (Asherman syndrome)
D. Imperforate hymen
E. Transverse vaginal septum
F. Cervical agenesisisolated
G. Cervical stenosisiatrogenic
H. Vaginal agenesis---isolated
I. Endometrial hypoplasia or aplasiacongenital

III. Hypothalamic causes

A. Dysfunctional
1. Stress
2. Exercise
3. Nutrition-related
Weight loss, diet, malnutrition
Eating disorders (anorexia nervosa, bulimia)
4. Pseudocyesis
B. other disorders
1. isolated gonadotropin deficiency
Kallman syndrome
Idiopathic hypogonadotropic hypogonadism
2. infectionTB

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COMPARTMENT I:
Disorders of the outflow tract or uterus

Mullerian anomalies
Imperforate hymen
Transverse vaginal septum
Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser Syndrome)
Androgen Insensitivity
Asherman syndrome

*Imperforate Hymen

The hymen itself is formed from the proliferation of the sinovaginal bulbs,
becoming perforate before or shortly after birth
Results when this sheet of tissue fails to completely canalize
Translucent thin membrane just inferior to the urethral meatus that
bulges with valsalva maneuver

Karyotype 46, XY
Male range testosterone level
Tx: gonadectomy after puberty + HRT

Difference between Mulalrian Agenesis and AI

Mullerian
Androgen
Agenesis
Insensitivity
Karyotype
46, XX
46, XY
Heredity
Not known
Maternal X-linked
recessive, 25% risk of
affected child, 25%
risk of carrier
Sexual hair
Normal female Absent to sparse
Testosterone
Normal female Normal to slightly
elevated male
Other anomalies
Frequent
Rare
Gonadal neoplasia Normal
5% incidence of
incidence
malignant tumors

*Transverse Vaginal Septum

Horizontal wall of tissue that has formed during embryologic

development and essentially creates a blockage in the vagina
Occurs between the upper one-third and lower two-thirds of the vaginal
canal
Resection of septum

*Mayer-Rokitansky-Kuster-Hauser Syndrome
(Utero-vaginal Agenesis)

15% of primary amenorrhea

Normal secondary development and external female genitalia
Normal female range testosterone level
Absent uterus and upper vagina and normal ovaries
Karyotype: 46, XX
15-30% renal, skeletal, and middle ear anomalies

*Androgen Insensitivity

Normal breasts but no sexual hair

Normal looking female external genitalia
Absent uterus and upper vagina

COMPARTMENT II:
Disorders of the Ovary

Gonadal Dysgenesis
a. Chromosomally abnormal
Classic Turner Syndrome (45XO)
Turner variants (45XO/46XX), (46X-abnormal X)
Mixed Gonadal Dysgenesis (45XO/46XY)
b. Chromosomally normal
46 XX (Pure Gonadal Dysgenesis
46 XY (Swyers Syndrome)

*Typical features of Turner Syndrome

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Multiple cell lines of varying sex chromosome composition

Appear normal, attaining normal stature before premature menopause is
experienced (accelerated atresia)
Patients are short

*Gonadal Agenesis

No c omplicated clinical problems accompany the gonadal failure due to

agenesis
Viral and metabolic influences in early gestation or undiscovered genetic
mutations are suspected
Surgical removal of the gonadal streaks is necessary to avoid the
possibility of neoplasia

*Premature Ovarian Failure

*Gonadal Dysgenesis

Gonadal dysgenesis associated with a normal karyotype is also linked to

neurosensory deafness (Perrault syndrome)
Pure gonadal dysgenesis indicates the presence of bilateral streak
gonads, regardless of karyotype
Mixed gonadal digenesis indicates testicular tissue on one side and a
streak gonad on the other

*XY Gonadal Dysgenesis (Swyers Syndrome)

Female patient with XY karyotype

Palpable mullerian syndrome
Normal female testosterone level
Lack of sexual development

*Mosaicism

Early depletion of ovarian follicles before the age of 40

Etiology: unknown but maybe due to genetic disorder with an increased
rate of follicle disappearance
Most common abnormalities: 45X and 47XXY, followed by mosaicism
Hormonal therapy recommended

*Radiation

Ovarian dose

Sterilization effect

6 rads
150 rads
250-500 rads
500-800 rads
Over 800 rads

No effect
Smoke risk over age 40
Ages 15-40 , 60% srterilized
Ages 15-40, 60-70% sterilized
100% permanently sterilized

*Chemotherapy
Alkylating agentsvery toxic to the gonads
Inverse relationship between the dose required for ovarian failure and
age at the start of therapy

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COMPARTMENT III:
Disorders of the Anterior Pituitary

Diagnostic approach to secondary amenorrhea

Hypogonadism and delayed puberty warrant brain evaluation by MRI

Obtain Beta hCG
Non-functioningadenoma: microadenoma
Pituitary prolactin secreting adenomas
Sheehans syndrome
Positive
Negative
Acute infarction and necrosis of the pituitary gland due to postpartum
hemorrhage and shock
Failure of lactation and loss of pubic and axillary hair
ObtainWeight/height, PRL, FSH and
Pregnancy
if indicated, testosterone or TSH
Hypothalamic amenorrhea (hypogonadotropic hypogonadism)
Deficiency in GnRH pulsatile secretion
Frequently associated with stress
Abnormal
Elevated
Elevated
Elevated
Higher proportion of underweight women and previous menstrual
ht/wt
PRL
FSH
testosterone
irregularity
Displays the endocrine, metabolic and psychological characteristics
suggesting the presence of a subclinical eating disorder
Chronic hypothalamic anovulation
Evaluate
Ovarian
<200
>200
Excessively
Obese
Stress
hypothyroidism,
failure
mg/dl
mg/dl
thin
drugs, renal failure
Increased exercise levels
Anorexia nervosa
Examine for possible
MRI scan of
Estrogen/
Ovarian hyperPelvis
Head trauma
dietary/nutritional
hypothalamus
progestin
androgenism
UTZ and
Space-occupying lesions
manipulations, evaluate
and pituitary
replacement
adrenal

*High serum FSH

Indicates the presence of ovarian failure

This test should be repeated monthly on three occasions to confirm
persistent elevation
A karyotype should be considered in most women of secondary
amenorrhea age 30 years or younger to rule out complete or partial
deletion of the X chromosome, or presence of any Y chromosome
material

for adrenal
hyperandrogenism

CT
Treat with
dopamine agonist

Suppress ovarian
androgen
secretion with OCs

History of D&C
preceding amenorrhea,
normal PRL and FSH

Ashermann
syndrome

Hysteroscopy and
hysterosalpingogram

Trial of
estrogen/progestin to
stimulate withdrawal
bleeding