100

Amenorrhea
BASIC INFORMATION
DESCRIPTION
Amenorrhea means absence of menstruation.
It is classified as either primary or secondary
depending on whether the patient has had previous menstrual cycles.


Primary amenorrhea is defined as the
absence of menses by age 16 in the presence of secondary sexual characteristics.
However, in the absence of these secondary
sexual features by the age of 14 years, one
should begin the workup for primary amenorrhea.


Secondary amenorrhea is the absence of
menses for more than six months in a patient
who has had previous normal progesterone
withdrawal cycles. The duration of amenorrhea required for the diagnosis of secondary
amenorrhea varies somewhat depending on
the source.
ICD-9CM CODES
626.0 Absence of menstruation
ICD-10CM CODES
N91.2 Amenorrhea, unspecified

EPIDEMIOLOGY &
DEMOGRAPHICS
Incidence of primary amenorrhea and secondary amenorrhea in the U.S. is <1% and
5% to 7%, respectively.
There is no racial or ethnic predilection.
ETIOLOGY
Physiologic amenorrhea
1. Pregnancy
2. Lactation
3. Menopause
Pathologic amenorrhea
A. Primary amenorrhea

1. Hypergonadotropic hypogonadism

a. Turners syndrome

b. Pure gonadal dysgenesis

c. Autoimmune oophoritis

d. 
17,20-desmolase deficiency or
17-hydroxylase deficiency

e. Galactosemia

2. Eugonadism (Table A1-45)

a. Mllerian agenesis

b. Transverse vaginal septum

c. Imperforate hymen

d. 
Androgen insensitivity syndrome
(AIS) (1%)

e. 5-alpha reductase deficiency

f. 
Polycystic ovarian syndrome
(PCOS)

g. 
Adult-onset congenital adrenal
hyperplasia (CAH)

h. Cushings syndrome

i. Hypothyroidism

3. Hypogonadotropic hypogonadism

a. Constitutional delay

b. Hypothalamic disorders

c. Pituitary diseases

d. Other CNS diseases

Secondary amenorrhea
1. Ovarian diseases

a. PCOS

b. Iatrogenic (oophorectomy, S/P radiation,
chemotherapy)
c. 
Primary ovarian insufficiency (previously premature ovarian failure [POF])

d. Ovarian tumors
2. Hypothalamic dysfunction

a. Functional (eating disorders, exercise,
stress)

b. Congenital GnRH deficiency

c. Infiltrative diseases (sarcoidosis, histiocytosis, lymphoma)
3. Pituitary diseases
a. 
Hyperprolactinemia (drug induced,
hypothyroidism, prolactinoma)

b. Craniopharyngiomas

c. Empty sella syndrome

d. Sheehans syndrome

e. S/P radiation

f. Infiltrative diseases
4. Ashermans syndrome
5. Others
Hypothyroidism, Cushings syndrome, adultonset congenital adrenal hyperplasia, drug
induced (Lupron Depot, Depo-Provera, levonorgestrel IUD, Danazol, etc.), chronic illnesses

PHYSICAL FINDINGS & CLINICAL

PRESENTATION
Turners syndrome
1. Usually presents with primary amenorrhea unless mosaic

2. Short stature

3. Epicanthic folds

4. Low-set ears

5. High-arched palate

6. Micrognathia
7. Sensorineural hearing loss

8. Otitis media
9. Webbing of the neck
10. Pigmented nevi
11. Square/shield chest
12. Widely spaced nipples
13. Absent breast development
14. Bicuspid aortic valve
15. Coarctation of aorta
16. Cubit valgus
17. Short fourth metacarpal
18. Hyperconvex nails
19. Leg edema
20. Renal abnormalities
21. Autoimmune disorders including thyroiditis
22. Diabetes mellitus
Pure gonadal dysgenesis
1. Unlike Turners syndrome has no dysmorphic features
Mllerian agenesis
1. Sporadic inheritance
2. Primary amenorrhea
3. Normal breast development
4. Normal pubic and axillary hair
5. Normal female external genitalia
6. Absent uterus and upper part of vagina
7. Ovaries present
8. 
Renal and vertebral anomalies in some
patients; renal agenesis should be evaluated

Transverse vaginal septum and imperforate

hymen
1. Primary amenorrhea
2. 
Progressive cyclic lower abdominal
pain
3. Imperforate hymen or transverse vaginal
septum on pelvic examination
4. Perirectal fullness from hematocolpos
5. 
Imaging with MRI identifies level of
obstruction
Androgen insensitivity syndrome
1. Primary amenorrhea
2. 
X-linked recessive inheritance in some
patients
3. Normal breast development
4. Absent pubic and axillary hair
5. Testis may be present in the groin or inguinal canal
6. Uterus and vagina absent
7. No associated renal or vertebral anomalies
Adult-onset congenital adrenal hyperplasia
1. 
Commonly seen in Ashkenazi Jewish,
Inuit Native American, French Canadian,
Mexican population
2. Mimics the presentation of PCOS
3. Features of hyperandrogenism (virilization,
hirsutism, acne)
4. Hypertension
5-alpha reductase deficiency
1. Primary amenorrhea
2. Undergo striking virilization at puberty
PCOS
1. Usually presents with secondary amenorrhea and oligomenorrhea
2. Features of hyperandrogenism
3. Obesity (60% to 80% of PCOS patients)
4. Infertility
5. Insulin resistance, predisposition to type II
diabetes mellitus
6. Association with the metabolic syndrome


Cushings syndrome (rare disorder, prevalence 1/1,000,000)
1. Secondary amenorrhea
2. Features of hyperandrogenism
3. Abnormal fat distribution (dorsocervical fat
pad [buffalo hump], spider legs, significant
central obesity)
4. Abdominal striae due to weakening of skin
integument
5. Easy bruising
6. Hypertension
7. Proximal muscle weakness
Hypothyroidism

1. Secondary amenorrhea

2. Lethargy

3. Constipation

4. Decreased appetite

5. Weight gain

6. Cold intolerance

7. Hair loss

8. Dry skin

9. Hypotension
10. Bradycardia
Primary ovarian insufficiency (previously premature ovarian failure)
1. Secondary amenorrhea prior to the age of
40
2. History of oophorectomy or pelvic radiation
or chemotherapy

Amenorrhea
TABLE A1-45 Congenital Anatomic Causes of Primary Amenorrhea with Normal Breast Development*
Mllerian Agenesis

Patients with primary amenorrhea

Patients with primary amenorrhea and apparent
obstruction or absence of
vagina
Chromosomes
Gonads
Serum testosterone
Vagina

15%

1%

3%

1%

75%

5%

15%

5%

46,XX
Ovaries
Normal female level
Absent or shallow

46,XY
Testes
Normal male level (high)
Absent or shallow

Axillary/pubic hair

46,XX
Ovaries
Normal female level
Obstructed by thin membrane, which may look
blue from hematocolpos
+

Cyclic pain
Uterus
Mass

Absent or rudimentary

Absent unless AI is incomplete

46,XX
Ovaries
Normal female level
Obstructed by septum which
may be thick or thin, high
or low
+

+
+
+
Can present with acute urinary retention

Introitus bulges with Valsalva

maneuver
Associated anomalies

+
+
+
Can present with acute urinary retention as hematocolpos mass obstructs
urethra

Urinary tract and skeletal

Treatment

Vaginal dilation or surgical

neovagina

Inguinal hernias; gonadal

malignancy in adulthood
Gonadectomy after age
16-18 yr
Vaginal dilation or surgical
neovagina

Fertility

Advanced reproductive technology required; invitro

fertilization surrogate
with uterus to gestate
pregnancy

Major urinary tract abnormalities in 15%

Surgical approach depends
on extent and location of
septum; may be extensive; should be done as
soon as possible
Variable, low septa have a
better prognosis than do
high septa

Possibly some increase in

urinary tract abnormalities
Excision of hymen as soon
as possible; diagnostic
needle aspiration contraindicated because of risk
of infection
Usually fertile

Not fertile

Transverse Vaginal
Septum

Imperforate Hymen

+, Present; , absent; , may be present or absent.

*Cervix not visible on pelvic examination. Short vagina; may be absent or obstructed.
Data from Reindollar RH, Byrd JR, McDonough PG: Delayed sexual development: a study of 252 patients, Am J Obstet Gynecol 140:371, 1981.
Sometimes useful in differentiating Mllerian agenesis from androgen insensitivity.
From Kliegman RM etal: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier.

3. Vasomotor symptoms
4. Dry, thin vaginal mucosa without rugosity
5. 
Associated autoimmune or karyotypic
abnormalities possible
Hyperprolactinemia
1. Usually presents with secondary amenorrhea
2. 
History of use of drugs such as antipsychotics, oral contraceptive (OC) pills,
antidepressants, antihypertensives, H2
blockers, opioids, etc.
3. 
Pituitary adenomas may be associated
with headache, vomiting, vision changes
4. Galactorrhea
Sheehans syndrome
1. History of secondary amenorrhea following postpartum hemorrhage
2. Failure of lactation
3. Other features of hypopituitarism
Ashermans syndrome
1. History of D&C
2. Secondary amenorrhea
3. Recurrent miscarriage/infertility

Functional hypothalamic disorders

1. Usually presents with secondary amenorrhea
2. History of eating disorders, severe exercise or stress
3. Use of street drugs
Kallmanns syndrome
1. Usually presents with anosmia, congenital
defect of development of both the GnRH
neurons and olfactory placode

DIAGNOSIS
First step in the workup of amenorrhea is to rule
out pregnancy by serum/urine pregnancy test.
Diagnostic workup depends on history and
physical.
Physical examination, determining the presence or absence of advanced breast Tanner
stage and presence or absence of uterus
can help guide evaluation (e.g., presence of
breasts but absence of uterus can only be
Mllerian agenesis or androgen insensitivity

syndrome).Primary amenorrhea (Fig. EA1-68

and Box EA1-10):
1. Pelvic ultrasonography or MRI to detect
any anatomic abnormalities of uterus, cervix, ovaries, or vagina. At times examination under anesthesia is needed to assess
the pelvic organs.
2. Karyotyping (46,XX in Mllerian agenesis;
46,XY in AIS; 45,XO in Turners syndrome)
is done when uterus is absent or Turners
syndrome is suspected.
3. Serum FSH, TSH/FT4, prolactin, estradiol:
FSH 40 mIU/ml along with estradiol <20
pg/ml is indicative of primary ovarian
insufficiency.
Prolactin >200 ng/ml is suggestive of
prolactinoma. Lower levels may also
be associated with prolactinoma.
Threshold levels may vary by laboratory, and providers are advised to
become familiar with their institutions
normal range.

Diseases
and Disorders

Diagnosis

Androgen Insensitivity
(AI)

101

102

Amenorrhea
Measure hCG

Present

Absent

Pregnancy

Progesterone
administration

No bleeding

Bleeding

1 or 2 months of
estrogen followed
by progesterone

Has patient
experienced marked
weight loss?

Yes

No

Evaluate for
hyperthyroidism,
adrenal insufficiency
nutritional disorders,
systemic illness

No bleeding

Endometrial lining
disorder

Is patient hirsute or
virilized?

No

Yes

FSH, PRL

FSH, LH, testosterone, DHEAS

FSH

Ovarian
failure

NL or FSH
PRL

LH,
NL or FSH
DHEAS
or testosterone

Pituitaryhypothalamic
disorder

Testosterone
NL DHEAS

Testosterone
and DHEAS

Ovarian
neoplasm

Dexamethasone

Polycystic
ovarian disease

DHEAS
suppresses

DHEAS does
not suppress

Adrenal
hyperplasia

Adrenal
neoplasm

FIGURE A1-69 Evaluation of secondary amenorrhea. DHEAS Dehydroepiandrosterone-sulfate; FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; LH, luteinizing hormone; NL, normal; PRL, prolactin; , increased; , markedly increased; , decreased. (From Andreoli TE [ed]: Cecil essentials of medicine, ed 7,
Philadelphia, 2008, Saunders.)

4. Check serum testosterone (male range in

AIS; female range in Mllerian agenesis)
when uterus is absent or in presence of
features of hyperandrogenism.
5. 
17-alpha hydroxyprogesterone level in
presence of features of hyperandrogenism to rule out CAH. In addition to high
level of 17 alpha hydroxyprogesterone due
to compromised 21-hydroxylase activ-

ity, these patients have elevated level of

serum progesterone and deoxycorticosterone, hypernatremia, and hypokalemia.
6. MRI of head in presence of:
Primary hypogonadotrophic hypogonadism.
1. Hyperprolactinemia.
2. Visual field defects.
3. Headaches.
4. Signs of hypothalamic-pituitary dysfunction.

Secondary amenorrhea (Fig. A1-69):

1. Serum FSH, TSH/FT4, prolactin, estradiol:
Low serum FSH with low estradiol
indicates hypogonadotropic hypogo
nadism.
High serum FSH with low estradiol suggests hypergonadotropic hypogonadism.
Progesterone withdrawal bleeding.

Amenorrhea

TREATMENT
The treatment of amenorrhea depends on the
etiology, as well as the aims of the patient,
such as a desire to treat hirsutism or to
become pregnant.


In the absence of pregnancy, withdrawal
bleeding may be induced in the majority of
patients with amenorrhea using 5 to 10 mg
of medroxyprogesterone for 10 days.
Estrogen replacement along with calcium and
vitamin D should be instituted in essentially
every patient with hypogonadism to avoid
osteoporosis. Women with a uterus require
continuous or intermittent progesterone
administration to protect against endometrial
hyperplasia or cancer. Frequently, it is easiest
to prescribe combination OC pills. For most
patients, continuation until 50 years, the
usual age of menopause, seems reasonable.

Young women in whom secondary sex characteristics have failed to develop fully should
be exposed initially to very low dose estrogen
(0.3 mg of conjugated equine estrogen or
equivalent) given unopposed daily for 6 mo
with incremental dose increases at 6-mo
intervals until the required maintenance dose
is achieved. Cyclic progesterone therapy, 12
to 14 days per month, should be instituted
once vaginal bleeding ensues.
Most patients with anatomic abnormalities
will require surgical correction. Creation of
a new vagina for patients with Mllerian
agenesis is usually delayed until the woman
is emotionally mature and ready to participate in the serial dilation or postoperative
care required to maintain vaginal patency.
However, if adequate correction is impossible, pregnancy will often require a surrogate to carry a gestation. One should not
forget to look for the associated urogenital
anomalies, such as renal agenesis, in these
patients and, when present, treat them
appropriately.
In patients with androgen insensitivity syndrome, the incidence of gonadal malignancy
is 22%. However, it rarely occurs before the
age of 20. Gonadectomy is performed by
laparoscopy following breast development
and the attainment of adult stature. In the
absence of a uterus these individuals only
need estrogen replacement without progesterone.
Women with adult-onset CAH may be treated
with low-dose corticosteroids in addition to
sex steroids to partially block ACTH stimulation of adrenal function and thereby decrease
overproduction of adrenal androgens.
Universal treatment of adult-onset CAH with
corticosteroids is controversial.
Patients with primary ovarian insufficiency
(POI) will need estrogen and progesterone
replacement. These patients will require
invitro fertilization using donor oocytes to
conceive. These patients have an increased
risk of osteoporosis and heart disease. It
can also be associated with autoimmune
disorders such as hypothyroidism, Addisons
disease, and diabetes mellitus. Therefore,
fasting blood glucose, TSH, and, if clinically
appropriate, morning cortisol should be measured. In the presence of a Y chromosome,
removal of gonadal tissue is recommended
at the time of diagnosis to avoid gonadal
tumors.
Hypothyroidism should be treated with thyroid replacement.
Hyperprolactinemia is treated by avoiding
the culprit drugs or by giving dopamine
agonists, such as bromocriptine or cabergoline. Pituitary adenomas rarely require
surgery but surgery may be performed if
secondary deficits such as visual changes
are observed, when they are resistant to
medical therapy, or the lesion is rapidly
growing.


Treatment of hypothalamic amenorrhea
depends on the etiology. Patients with eating disorders or who exercise excessively

will require behavioral modification and

nutritional counseling. Elite athletes may
choose not to alter their exercise regimens
and will therefore require estrogen treatment and prevention of osteoporosis. When
associated with infertility, ovulation induction with clomiphene citrate, exogenous
gonadotropins, or pulsatile GnRH therapy
should be offered.
The primary treatment of PCOS is weight loss
through diet and exercise. Other treatment
options include:
1. Use of OC pills or cyclic progestational agents
to help maintain a normal endometrium.
2. 
Insulin-sensitizing agents such as metformin to reduce insulin resistance and
improve ovulatory function. Recent studies suggest that insulin-sensitizing agents
may not be as effective in improving
ovulatory effort.
3. Oral contraceptives and/or spironolactone
to treat hyperandrogenism.
4. Clomiphene citrate or an aromatase inhibitor such as letrozole to induce ovulation.
In patients with Ashermans syndrome, hysteroscopic lysis of intrauterine adhesions
is followed by administration of long-term
exogenous estrogen to stimulate regrowth of
endometrial tissue.
Geneticist consult is given in patients with
hereditary causes of amenorrhea.
Psychiatrist consult is needed in patients with
major depression, anorexia nervosa, bulimia
nervosa, or other major psychiatric disorders.

COMPLICATIONS
Osteoporosis
Endometrial hyperplasia and uterine cancer
Infertility
PROGNOSIS
Depends on the primary cause of amenorrhea
PATIENT EDUCATION
Patients with amenorrhea should be reassured
that this is, in and of itself, not a concern.
All women with an intact endometrium should
understand the risks of unopposed estrogen
action, whether the estrogen is exogenous
such as through hormone therapy, or endogenous such as PCOS.
Hypoestrogenic women should be counseled
about the importance of estrogen replacement to protect against bone loss.
Potential for future childbearing should be
discussed.
SUGGESTED READINGS
Available at www.expertconsult.com
RELATED CONTENT
Infertility (Related Key Topic)
Pituitary Adenoma (Related Key Topic)
Polycystic Ovary Syndrome (Related Key Topic)
Sheehans Syndrome (Related Key Topic)
Amenorrhea (Patient Information)
AUTHOR: HEMANT K. SATPATHY, M.D.

Diseases
and Disorders

10 mg medroxyprogesterone is given for

10 days.
Withdrawal bleeding suggests euestrogenic anovulation in presence of normal
end organ (outflow tract) and ovarian
function.
Estrogen-progesterone withdrawal bleeding:
In the absence of progesterone withdrawal
bleeding, the patients are exposed to 25
to 35 days of estrogen (0.625 to 2.5 mg
Premarin daily) followed by 10 days of
medroxyprogesterone.
Withdrawal bleeding indicates hypogonadism.
Absence of bleeding suggests defects with
end organ (e.g., Ashermans syndrome).
Serum LH, testosterone and DHEA-S:
When features of hyperandrogenism seen
these tests are ordered.
Serum testosterone >200 ng/ml suggests
androgen-producing adrenal or ovarian tumors (high index of suspicion with
moderate elevation; threshold value not
required in cases of ovarian or adrenal
tumors). This level may be mildly elevated
in patients with PCOS.
DHEA-S >700 mcg/dl suggests adrenal origin over ovarian (high index of suspicion
with moderate elevation; threshold value
not required in cases of ovarian or adrenal
tumors).
LH/FSH ratio >2 may be present in patients
with PCOS, although this is not part
of diagnostic criteria according to the
Rotterdam consensus conference.


Pelvic ultrasound when PCOS or ovarian
tumor suspected.


Abdominal CT when adrenal tumor suspected.
MRI of head when indicated.


HSG, sonohysterography, or diagnostic
hysteroscopy in patients with suspected
Ashermans syndrome.
Karyotyping is indicated when primary ovarian insufficiency occurs before the age of 40.
Other tests which are rarely needed:
Serum transferrin when hemochromatosis is
suspected.
Serum ACE when sarcoidosis is suspected.

103

Amenorrhea
EVIDENCE
Abstract[1]

Context:
In the general population, about 30% of asymptomatic women have
polycystic ovary-like abnormalities (PCO-L), i.e., polycystic ovarian morphology (PCOM) at ultrasound and/or increased anti-Mllerian hormone
(AMH) serum level. PCOM has also been reported in 30%-50% of women
with functional hypothalamic amenorrhea (FHA).
Objective:
The aim of this study was to verify whether both PCOM and excessive
AMH level indicate PCO-L in FHA and to elucidate its significance.
Design:
We conducted a retrospective analysis using a database and comparison
with a control population.
Setting:
Subjects received ambulatory care in an academic hospital.
Patients:
Fifty-eight patients with FHA were compared to 217 control women with
nonendocrine infertility and body mass index of less than 25 kg/m2.
Interventions:
There were no interventions.
Main Outcome Measures:
We measured serum testosterone, androstenedione, FSH, LH, AMH, and
ovarian area values. The antral follicle count (AFC) was used as a binary
variable (i.e., negative or positive) because of the evolution of its sensitivity over the time of this study. The ability of these variables (except AFC)
to detect PCO-L in both populations was tested by cluster analysis.
Results:
One cluster (cluster 2) suggesting PCO-L was detected in the control
population (n = 52; 24%), whereas two such clusters were observed in
the FHA population (n = 22 and n = 6; 38 and 10%; clusters 2 and 3,
respectively). Cluster 2 in FHA had similar features of PCO-L as cluster
2 in controls, with higher prevalence of positive AFC (70%) and PCOM
(70%), higher values of ovarian area and higher serum AMH (P <0.0001
for all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in
FHA was peculiar, with frankly elevated AMH levels. In the whole population (controls + FHA), PCO-L was significantly associated with lower FSH
values (P <0.0001).
Conclusion:
PCO-L in FHA is a frequent and usually incidental finding of unclear significance, as in controls. The association of PCO-L with hypothalamic
amenorrhea should not lead to a mistaken diagnosis of PCOS.
Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age and is associated with androgenization, anovulation, and the metabolic syndrome. Robin etal make a link between
functional hypothalamic amenorrhea (FHA), which is a frequent cause
of anovulation, hypoestrogenism, and negative energy balance from excessive exercise leading to hypoinsulinism (in contrast to insulin resistance in PCOS). In FHA, luteinizing hormone levels tend to be higher than
follicle-stimulating hormone levels as observed in PCOS.
This also results in polycystic ovarian morphology (PCOM), which is observed in 30% to 50% of women with FHA. The presence of PCOM in
women with FHA might lead to the mistaken diagnosis of PCOS. Another
confounding finding in both disorders is that anti-Mllerian hormone
(AMH) might be elevated in both, because AMH is the most common
endocrine abnormality associated with PCOM. PCO-like disorder is also
common in the general population. The authors observed the occurrence
of PCOM in about 70% of women with FHA.
Based on their study, they do not think that the association of PCO-like
disorder with hypothalamic amenorrhea should be mistakenly diagnosed
with PCOS.[1-5]
AW Meikle, MD

103.e1

Evidence-Based References
Scheid JL, De Souza MJ: Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines, Med Sport Sci
55:82102, 2010.
Robin G, Gallo C, Catteau-Jonard S, etal.: Polycystic ovary-like abnormalities
(PCO-L) in women with functional hypothalamic amenorrhea, J Clin Endocrinol
Metab 97:42364243, 2012.
Dumesic DA, Abbott DH, Padmanabhan V: Polycystic ovary syndrome and its
developmental origins, Rev Endocr Metab Disord 8:127141, 2007.
Meczekalski B, Czyzyk A, Podfigurna-Stopa A, etal.: Hypothalamic amenorrhea in a Camurati-Engelmann diseasea case report, Gynecol Endocrinol
29:511514, 2013.
Santoro N: Update in hyper- and hypogonadotropic amenorrhea, J Clin Endocrinol
Metab 96:32813288, 2011.
Caronia LM, Martin C, Welt CK, etal.: A genetic basis for functional hypothalamic
amenorrhea, N Engl J Med 364:215225, 2011.

SUGGESTED READINGS
Gordon CM: Functional hypothalamic amenorrhea, N Engl J Med 363:365371,
2010.
Klein DA, Path MA: Amenorrhea: an approach to diagnosis and management, Am
Fam Physician 87(11):781788, 2013.
Master-Hunter T, Heiman DL: Amenorrhea: evaluation and treatment, Am Fam
Physician 73(8):13741382, 2006.
Practice Committee of the American Society for Reproductive Medicine: Current
evaluation of amenorrhea, Fertil Steril 82(suppl 1):S3339, 2004.

Amenorrhea

103.e2

Normal/decreased

MRI of pituitary gland,

prolactin level

Elevated

Primary gonadal
disease

Elevated

Hypothyroidism
(primary)

Decreased/normal

Hypothyroidism
(secondary)

FSH

Infantile

TSH
Sexual
development

Pelvic
ultrasound

Normal sexual
development

MRI of brain

Serum prolactin
level

Elevated

Serum hCG

Positive
(pregnancy)

MRI of pituitary

FIGURE EA1-68 Evaluation of primary amenorrhea. FSH, Follicle-stimulating hormone; hCG, human chorionic gonadotropin; MRI, magnetic resonance imaging;
TSH, thyroid-stimulating hormone. (From Ferri FF: Ferris best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 2, Philadelphia, 2009,
Mosby.)

BOX EA1-10Primary Amenorrhea

Diagnostic Imaging
Best Test
MRI of pituitary/hypothalamus with gadolinium when hypothalamic/pituitary lesion
is suspected
Ancillary Tests
Pelvic ultrasound

Laboratory Evaluation
Best Tests
FSH
Prolactin
TSH
Ancillary Tests
Serum hCG

FSH, Follicle-stimulating hormone; hCG, human chorionic gonadotropin; MRI, magnetic resonance imaging; TSH,
thyroid-stimulating hormone.
From Ferri F: Ferris best test: a practical guide to clinical laboratory medicine and diagnostic imaging, ed 3,
Philadelphia, 2014, Mosby.