Year 3, 2nd Semester AY 2017-2018 // April 17, 2018

GYNECOLOGY
3.09 – Amenorrhea
Dr. Tongco

OUTLINE II. MENSTRUATION TODAY

I. Menstruation: Myths and Taboos • The presence of menstruation means a normal or intact:
II. Menstruation Today o Hypothalamic-Pituitary-Ovarian connection
IIII. Introduction to Amenorrhea o Outflow tract (uterus, cervix, vagina)
IV. Primary Amenorrhea
A. Turner Syndrome
B. Swyer Syndrome
C. Imperforated Hymen
D. Primary Ovarian Insufficiency
E. Mayer-Rokitansky-Kuster-Hauser Syndrome
V. Secondary Amenorrhea
A. Polycystic Ovarian Syndrome
B. Functional Hypothalamic Amenorrhea
C. Hyperprolactinemia due to Pituitary Adenoma
D. Androgen Insensitivity Syndrome
VI. Causes of Amenorrhea
VII. Tips in Amenorrhea Work-up
VIII: Work-up of Primary Amenorrhea
IX: Work-up of Secondary Amenorrhea
X: Treatment Guidelines of Amenorrhea Figure 1: Hypothalamic-Pituitary-Ovarian Axis. You can see that
the hormones produced in the hypothalamus and the pituitary
XI: Summary
gland would drive the ovary to produce the hormones estrogen
and progesterone, which act on the endometrium to cause
OBJECTIVES proliferation and secretory changes; and eventually, with the
withdrawal of the progesterone, leads to menstruation. That’s why
if menstruation is absent, it means there is something wrong with
At the end of the lecture, the student should be able to:
the HPO axis or the outflow tract of the patient.
1. Define Amenorrhea;
2. Enumerate and define the types of amenorrhea;
 GnRH pattern should be pulsatile to increase FSH and LH in a
3. Enumerate the different causes of amenorrhea and their
clinical features; normal menstrual cycle.
4. Explain the importance of diagnosis and treatment of
amenorrhea; III. INTRODUCTION TO AMENORRHEA
5. Explain the work-up for primary and secondary amenorrhea;
6. Discuss the rationale for the laboratory tests; and
7. Discuss the treatment guidelines. A. Definition

 From book (Book used) • It is the absence of menses

 From old trans (Lecturer) • It could be a sign of abnormality in the:
 Highlighted by lecturer o Hypothalamic-Pituitary-Ovarian connection
o Outflow tract (uterus, cervix, vagina)

I. MENSTRUATION: MYTHS AND TABOOS B. Types of Amenorrhea

 Leviticus 19: “Whenever a woman has her menstrual • Physiologic – seen in pregnancy and lactation, menopause
period, she will be ceremonially unclean for seven days. • Pathologic
Anyone who touches her during that time will be unclean o Primary
until evening.” o Secondary
 In some historic cultures, a menstruating woman was • In this discussion, when we say amenorrhea, we would be
considered sacred and powerful: increased psychic abilities referring to the pathologic type, not the physiologic type, as
and can heal the sick. a shortcut.
 Menstruation triggers psychiatric tendencies.
 Many Asian women believe that the heavier the menses, the C. Primary Amenorrhea
better… to cleanse the body.
 Menstruation becomes an excuse (e.g. not come to work). • Never had menses
• No menarche
• Watch out for in the following cases:

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Subject Trans Heads: MITCH ABAD | JK | NIKKI
 GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)

o 15-years-old, no menses, yet with secondary E. Why Treat Amenorrhea (Pathologic)?

characteristics
o 13-years-old, no menses and no secondary sexual
• Incidence of pathologic amenorrhea in 3-4% of women
characteristics
• May be a sign of a more serious underlying disease
• Failure to treat may lead to a serious medical and surgical
complications
• Results in physical, mental, emotional, social and even legal
consequences

F. Categories of Amenorrhea

• Categorized based on gonadotropin and estrogen levels

Table 3. Categories of Amenorrhea (Dr.Tongco’s PPT 2018)

Types of Primary
Figure 2: Normal Puberty in Girls/Women. Normal puberty follows LH/FSH Estrogen
Hypogonadism Defect
this sequence: Thelarche (breast) →Growth spurt (height)
→Adrenarche (pubic hair) →Menarche (menstruation) Hypergonadotropic High Low Ovary

Table 1. Causes of Primary Amenorrhea (2018A) Hypothalamus/

Hypogonadotropic Low Low
Pituitary

Eugonadotropic Normal Normal Varied

 Hypergonadotropic: high FSH/LH

 Hypogonadism: low estrogen

IV. PRIMARY AMENORRHEA

A. Turner Syndrome (45XO)

• Case 1:
o Linda Hunt, 70 y/o, actress
o Turner syndrome, 45XO
o Infantile secondary sexual characteristics (e.g. little
breasts, no hair, infantile uterus)
o Small
o Could have received growth hormone to improve height

D. Secondary Amenorrhea

• Absent menses in a previously menstruating woman

o >/= 3 months, if with regular cycles
o >/= 6 months, if with irregular cycles

Table 2. Causes of Secondary Amenorrhea (2018A)

Figure 3: Linda Hunt

CLINICAL FEATURES
• 45XO or mosaic – streak gonads, small stature
• Hypergonadotropic Hypogonadism = Low Estrogen
o Due to incomplete development of her ovaries (ovaries
need two X’s to develop)
• History: Lacks pubertal development, normal intelligence

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Subject Trans Heads: MITCH ABAD | JK | NIKKI
 GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)

• PE: less than 5 feet, low set ears, webbed neck, broad o But then she started complaining of cyclic hypogastric
chest, infantile breasts, no axillary nor pubic hair; pain and a mass
reproductive tract is female but uterus is infantile. o Imperforate hymen with hematocolpos and hematometra
• Concerns: appearance, height, fertility; and consequences o Hymenotomy done → Menses came regular, monthly
of low estrogen which would be osteoporosis
• Diagnosis: FSH elevated (estrogen is low thus there is no
negative feedback), estrogen low, karyotyping
• Treatment: hormones to promote secondary sexual
development, growth hormone (to improve height), oocyte
donation and IVF (In-Vitro Fertilization; for fertility; look for a
donor for eggs, have it fertilized in the lab with a husband,
and the resulting embryo could be implanted in her uterus)

Figure 5: Patient IH

 Due to failure of degeneration of the epithelial cells of the

Figure 4: Karyotyping in Turner Syndrome.
B. Swyer Syndrome (45XY)
 Must be differentiated with Turner syndrome since they
present in the same way. They both have short statures and
infantile characteristics. The difference is that in Swyer, the
patient is male (XY)! They also have low-set ears and
webbed neck. Everything else from history to treatment is
the same.
 Differentiated from Turner syndrome through karyotyping
CLINICAL FEATURES
• Pure gonadal dysgenesis
o 45XY or mosaic – streak gonads, small stature
• The Y chromosome does not contain the gene that
determines the development of the testes. So, you
remember in embryology, if there are no testes, there is no
mullerian-inhibiting substance, and what develops is female
line. But because these individuals do not have
ovaries/testes/hormonal production, the female line is
infantile.
• Hypergonadotropic Hypogonadism = Low Estrogen
• History: lacks pubertal development, normal intelligence
• PE: less than 5 feet, infantile breasts, no axillary nor pubic
hair; reproductive tract is female but uterus is infantile.
o They are males with female internal and external
genitalia.
• Concerns: appearance, height, fertility
• Diagnosis: FSH elevated, estrogen low, karyotyping
• Treatment: hormones to promote secondary sexual
development, growth hormone, oocyte donation and IVF
C. Imperforated Hymen
• Case 2:
o IH, 13 y/o, 2nd year HS
o No menarche
o Felt very insecure with friends (since they are already
talking about their menses, but she hasn’t had them yet)
hymen
 Can be seen and resolved at birth. Maybe the pediatrician
did not see the condition, but this could have already
manifested at birth, possibly as an effect of high maternal
estrogen and progesterone which stimulates the secretion of
mucus; and so, at birth, the mucus may have been trapped
causing a bulge but resorbed and so baby becomes
asymptomatic. If you miss the opportunity to fix this, the next
opportunity would already be after puberty when the patient
is already symptomatic and complaining of pain.
CLINICAL FEATURES
• Normal pubertal development
• Cyclic pain +/- mass
• PE: Bulging bluish mass on introitus
• Treatment: hymenotomy
• Complications: infection, endometriosis (because if blood is
not able to flow out, it may flow back into the uterus,
fallopian tube and ovaries), acute abdomen
Figure 6: Imperforate Hymen Before and After Surgery. It’s a
bulging and bluish hymen (sign of an imperforate hymen). After
being perforated, what came out was something like Hershey’s
chocolate syrup – that’s old blood. Then they try to tie the edges
of the hymen to keep it open, to make an open vagina.
D. Androgen Insensitivity Syndrome (46XY)
• Case 3:
o IA, 28 y/o, newly married
o “Not PIA”
o With breasts but no pubic/axillary hair
o No uterus, no vagina
o Androgen insensitivity syndrome
o 46XY, male testosterone levels
o Divorce, gender?

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Figure 7: Patient IA. With breasts but no pubic/axillary hair
 Background: She is a model. Having no menstruation, she
welcomes it since it does not get in the way of her work. She
doesn’t have axillary hair and pubic hair, and she likes that
since she doesn’t have to shave. The problem is when she
got married, the nightmare started. Instead of fireworks, it
was as though nothing happened. Intercourse could not be
consummated. Penile penetration could not happen. Upon
consultation, they found out that she had Androgen
Insensitivity Syndrome (46XY), with ambiguous genitalia, a
large clitoris, no vagina (just a dimple), and a bulge in the
inguinal area (probably the testes). And so, her husband
filed for a divorce.
CLINICAL FEATURES
• X-linked recessive disorder (46XY)
• Defect in androgen receptors, but testes are normal
(inguinal area)
o Testosterone cannot act on the target organs because
the receptors are absent.
• Female phenotype: (+) breasts, no hair, external genitalia
but no vagina and uterus and with enlarged clitoris (>1cm,
clitoromegaly). This is because testosterone can be
converted into estrogen peripherally, in the fat.
• Diagnosis:
o Ultrasound: Absent uterus/vagina and ovaries
o Serum testosterone: normal male level
o Karyotype: 46XY
• Treatment: gonadectomy (in any scenario where there is a
Y chromosome, the treatment is to remove that gonad
because it has a high risk for malignant degeneration, i.e.
gonadoblastoma), gender reversal (if preferred),
neovagina (if she wants to remain a female)
 Genetically male (46XY)
E. Mayer-Rokitansky-Kuster-Hauser Syndrome (46XX)
• Case 4:
o MRKHS, 42y/o, married for 1 year
o Unsatisfactory sex
o 46XX
o No uterus, 1cm vaginal dimple
o Congenital absence of uterus
o Neovaginal reconstruction
Figure 8: Patient MRKHS
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Subject Trans Heads: MITCH ABAD | JK | NIKKI
GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)
 Background: She is actually a late bloomer. She married at
45. She’s not concerned with having children. Even if without
menstruation, she was not concerned. Pregnancy was not in
her dreams. Sex was not satisfying. On examination, she’s
completely female with 46 XX karyotype, with normal
hormones, but she has no uterus and vagina. Her genitalia
are female. She requested for a reconstruction of her vagina
because she longs for companionship. A neovagina was
done, and after, she said that she was never out of cloud
nine.
CLINICAL FEATURES
• Mullerian agenesis or congenital absence of the uterus
• Failure of the Mullerian duct development
• Normal ovaries
• 1 in 5000 females; 15% of primary amenorrhea (2nd most
common cause of primary amenorrhea; the most common
would still be gonadal dysgenesis or Turner syndrome)
• Normal height, thelarche, adrenarche
• PE: (+) breast and pubic hair, female external genitalia, no
vagina, no uterus
• Diagnosis: UTZ (no uterus), karyotype 46XX (female),
normal E2 levels (Since ovaries are normal)
• Treatment: vaginal dilators (if does not prefer a surgery, we
can just distend it), neovagina, surrogacy (if wants to have a
baby; they can get her eggs since she still has normal
ovaries, then fertilize in the lab and implant on a surrogate;
but is not allowed in the Philippines)
• Check: skeletal (especially the spine), kidneys (since
development of the kidneys go with that of the reproductive
tract), hearing loss
 Genetically female (46XX)
Figure 9: MRKHS. Laparoscopic view showing absence of
gonads, fallopian tubes, and uterus. There are also variants.
There can have a small uterus but the vagina is absent; or there
can be two vestiges of the uterus, but still no vagina. At times,
there can be a functional endometrium which can have
menstruation, and blood can’t come out. They present with a
mass, similar to imperforate hymen – cyclic pain, mass. What we
do is we suppress their menses or take this out if they don’t prefer
medications. Is it possible to connect it to an opening (i.e.
neovagina)? Sometimes it’s hard because of the distance – it’s a
very long way to connect from the uterus to the vaginal opening.
V. SECONDARY AMENORRHEA
• Remember, secondary amenorrhea –there is already menses
but, at some point, she missed her menses in those with

regular cycles, it’s ≥3 months; in those with irregular cycles,
it’s ≥6 months.
A. Polycystic Ovarian Syndrome
CASE 5:
34 y/o with infertility
• Irregular menses, acne, and hirsutism, polycystic
ovaries on ultrasound
• Obese
• No treatment → At 36 y/o (after 2 years), became
diabetic, had an episode of MI, and developed
endometrial carcinoma
• Amenorrhea from an underlying condition, having
medical and surgical consequences when left
untreated.
Clinical Features
• 20% of amenorrhea
• State of hyperinsulinemia and insulin resistance which
stimulates androgen production in the ovary
• May also have lifelong health concerns: heart disease, DM,
liver disease, endometrial cancer, infertility, poor pregnancy
outcome
• It seems that PCOS is the first sign of Diabetes, and it is
aggravated by obesity. There are lifelong concerns because
of this.
• Diagnosis based on the criteria: oligomenorrhea,
hyperandrogenism, polycystic ovaries in ultrasound,
Rotterdam Criteria for PCOS; laboratories showing:
2. Testosterone increased (d/t insulin resistance)
3. =/- obesity
4. Check 2hr 75g OGTT, lipids, liver function
• Treatment: prevent endometrial hyperplasia
(COC/progesterone – if patient has amenorrhea, we prevent
continuous exposure to estrogen without progesterone by
giving them progesterone); Then we treat the other medical
complication: prevent metabolic complications (weight
loss/metformin), treat acne and hirsutism with anti-androgens
/ cyproterone acetate, ovulation induction for fertility.
• Concerns: possible progression to endometrial
hyperplasia/cancer, infertility, very poor pregnancy outcomes
(every time she’s pregnant, always lead to abortion)
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Subject Trans Heads: MITCH ABAD | JK | NIKKI
GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)
Figure 10. Clinical Picture of PCOS, and Ultrasound Findings
B. Functional Hypothalamic Amenorrhea
CASE 6:
Karen, died at 32 y/o
• Singer
• Has Anorexia Nervosa
• Hypoestrogenic and amenorrhea: functional
amenorrhea
• Osteoporosis
• Possibly, due to her thinness or her lack of calories, she is
hypoestrogenic and amenorrheic because the brain senses
that if you do not have enough calories in you, the calorie
expenditure of your body would probably be distributed by
the brain to other organs that are vital to your survival, not for
reproduction.
• Absence of organic pathology (no tumors, or other
structural problems in the brain; in our case, it was just her
anorexia nervosa which led to a hormonal problem) and thus
termed functional – because there is a problem in the
function of the hypothalamus or the pituitary.
• Associated with abnormal GnRH pulses / LH pulses
• Causes: sudden and excessive weight loss (anorexia
nervosa / bulimia) or weight gain, excessive exercise, stress,
chronic illness, malnutrition
o You can see this condition in runners who do excessive
exercise, and those under stress (you guys!)
• Check estrogen levels: hypothalamic dysfunction VS
hypothalamic failure
o This is important because if she has low levels, you must
treat her and supplement her with estrogen replacement,
or else she may suffer from symptoms of estrogen
deficiency (e.g. CVD, cognitive decline, osteoporosis)
• Treat if hypoestrogenic– risk of osteoporosis
C. Hyperprolactinemia 2° to Pituitary Adenoma
CASE 7:
PA, 28 y/o
• Irregular and scanty menses
• Milky nipple discharge
• Headache, blurred vision
• Elevated serum prolactin
• CT scan: pituitary tumor
• Bromocriptine (dopamine agonist – inhibit
prolactin) →Decrease in tumor size, regular
menses
Clinical Features:
• Amenorrhea + Galactorrhea = Hyperprolactinemia
o This is a sign of a pituitary problem, since prolactin is
produced by this gland. Once present, ask the patient if
they have headache, seizures, blurring of vision, and
blindness. Eye symptoms appear because the gland is

close to the optic nerve and may impinge the nerve
when enlarged. This disrupts one’s peripheral vision
which may lead to vehicular accidents.
• Causes: pituitary adenoma secreting prolactin; high levels of
prolactin inhibiting GnRH secretion.
• Diagnosis:
o Symptoms: amenorrhea, milky nipple discharge,
headache, blurring of vision
o Laboratory: Prolactin elevated
o CT/MRI scan of pituitary: (+) tumor
• Treatment: microadenomas are treated with
Bromocriptine(an ergot-derived dopamine agonist, which
inhibits prolactin release); bigger tumors need surgery.
D. Primary Ovarian Insufficiency
CASE 7:
POI, 27 y/o, soon to be bride
• Irregular menses for 2 years
• Hot flushes
• Primary Ovarian Insufficiency due to an
autoimmune condition
• Elevated FSH
• Fertility
Clinical Features:
• Premature ovarian failure
• Menopause before age 40 (allowable age to have
menopause)
• Loss of ovarian follicles
• Causes: trauma (surgery), chemotherapy, radiation,
autoimmune oophoritis, or mutations
• Diagnosis: ANA, antithyroid antibodies, TSH; karyotype if <25
y/o
• Concerns: fertility, consequences of estrogen deficiency
(e.g. vasomotor symptoms, genitourinary symptoms,
osteoporosis, heart disease, cognitive decline, colon CA)
o For fertility, she could still get pregnant (be a surrogate
mother) but she would require donor oocytes.
• Treatment of underlying cause: HRT, oocyte donation
Figure 11. Histological Difference of Normal Ovary and Ovary in
POI. In the normal ovaries, you can see those big circles – those
are follicles and there are numerous follicles. On the other hand,
ovaries of a woman with POI consists mostly of fibrous tissue and
only a few follicles are present. The decrease in follicles may be
caused by an underlying medical condition – history of multiple
cystectomy (remove follicles),mutations. If it happens <25 years
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Subject Trans Heads: MITCH ABAD | JK | NIKKI
GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)
old, think of something chromosomal; >25 years old, it could be
because of insults or a medical condition.
VI. CAUSES OF AMENORRHEA
• After seeing all those cases, our conclusion would be
AMENORRHEA NEEDS INVESTIGATION!
• Amenorrhea could be caused by abnormalities in the ff:
o Hypothalamic-Pituitary-Ovarian connection
o Outflow tract (uterus, cervix, vagina)
HPO AXIS
• Trauma
• Drugs
• Chemotherapy
• Radiation
• Surgery
• Anoxia
• Tumors
• Infection
HYPOTHALAMUS
• GnRH Deficiency (Kallman Syndrome)
o Kallman Syndrome – patient’s only problem is
amenorrhea but she doesn’t know that she has a
problem with smell because her olfactory cells and her
GNRH neurons travel along the same tract during the
fetal development so if there is a defect in the tract of
the olfactory cell, GNRH neurons won’t be able to
migrate to the hypothalamus, thus, aside from
anosmia they will also have GNRH deficiency
o Test the patient via: smelling perfume and coffee
• Functional Hypothalamic amenorrhea: weight loss, eating
disorders, excessive exercise, stress, prolonged illness
• Hypothalamic dysfunction, Hypothalamic failure
• Other syndromes: Prader Willi, Lawrence-Moon-Biedl, Leptin
Mutations
HYPOTHALAMIC HYPOTHALAMIC FAILURE
DYSFUNCTION
• Normal estrogen levels • Low estrogen and FSH
• No CNS organic pathology • No CNS organic
• Abnormality in GNRH and pathology
LH pulses • Risk of osteoporosis
• Treatment: cycle • Treatment: hormone
regulation, ovulation replacement therapy
induction agents
It is important to specify if it a dysfunction or a failure. Because
which of them do we treat, dysfunction or failure? Of course, it’s
failure because there is low estrogen which puts them at risk for
CVD, cognitive decline, osteoporosis Alzheimer’s, colon cancer,
etc.
PITUITARY GLAND
In the pituitary, the most common reason would be TUMORS!
• Empty sella syndrome – pituitary resides in the sella turcica.
If this compartment is filled with CSF, and the pituitary cannot
be seen there – this is what you called an empty sella. Where
is it? It may have been pushed or flattened, and so this patient
cannot secrete the hormones that are released by this gland –
FSH, LH, Prolactin, ACTH, Growth Hormone, Oxytocin, etc.
• Genetic causes of hypopituitarism
• Others: hypothyroidism, hyperthyroidism, PCOS, diabetes
• Sheehan’s / Simmonds disease – these are insults to the
pituitary. Sheehan’s is when there is hemorrhage during
pregnancy, patient becomes anoxic and the pituitary suffers.
Simmonds is the same but occurs in nonpregnant patients.
o Presence of profound hypotension secondary to
massive bleeding during delivery
 GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)

o Blood supply to the pituitary decreases as a result of

the hypotension
o Thus, the pituitary gets damaged, further affecting all
the hormones released by the pituitary
o Patient presents with difficulty thriving
▪ Ex: thin, intolerance to cold, inability to breast feed
OVARY

Absent gonads – very rare; no gonads but appear female. Why do

they appear female? Because it‘s the default setting if there are
no gonads.
• Dysgenetic gonads (Turner/Swyer syndrome)
• Enzyme disorders
• Autoimmune disorders
OUTFLOW TRACT
Abnormal • AIS Figure 13: Examples of causes of amenorrhea, proving the cause
Mullerian • MRKH Syndrome of amenorrhea becomes a challenge.
Development • Cervical Agenesis
(Congenital)
VII. TIPS IN AMENORRHEA WORK-UP
Trauma/Infection • Cervical stenosis
• Intrauterine adhesions • #1 Rule out PREGNANCY!
o TB • Determine if Primary or Secondary
o Asherman’s syndrome – • REMEMBER! Primary if patient never had any menarche;
excessive curettage of the while secondary, patient was previously menstruating and
endometrium leads to scarring, there was cessation of menses.
no endometrium develops, no • If PRIMARY, think GENETIC (Chromosomal or enzyme
reaction to estrogen and deficiencies) or ANATOMIC (congenital).
progesterone -> no more • If SECONDARY, think ENDOCRINE or ANATOMIC
menstruation (acquired) disorders.
Congenital • Transverse Vaginal Septum • Identify level of abnormality: Hypothalamus, Pituitary,
Defects of the • Imperforate Hymen Ovarian, Uterine/Outflow tract
Urogenital SInus • Go by frequency of occurrence

Figure 12: Defects of the Urogenital Sinus. In development, the

mullerian duct fuses with the urogenital sinus, grows and
becomes the forerunner of the vagina. Before birth, it must Figure 14: Causes of primary amenorrhea. Almost half of the
canalize. If there is failure of canalization, the individual develops cases will be because of gonadal dysgenesis (Turner or Swyer).
a septum. It presents similarly with an imperforate hymen, but the The next will be mullerian agenesis (MRKH syndrome). Some will
obstruction is anywhere in the vaginal tract. Thus you do not see just have a physiologic delay.
a bulge, rather, upon internal examination, you find that the
vagina is short, and there could also be hematocolpos and
hematometria.

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Subject Trans Heads: MITCH ABAD | JK | NIKKI
 GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)

Figure 15: Causes of secondary amenorrhea. Most common

would be PCOS, and the next would be functional (stress,
exercise, eating disorders). Figure 17: Work-up in cases of Breast (-) and Uterus (+). BOX 1:
Remember Linda Hunt? She has infantile breasts but an intact
• History: signs/symptoms of pregnancy, pubertal uterus. Karyotyping reveals gonadal failure. CT scan may be
development, family history (genetic conditions), illnesses, normal. BOX 2: For Hypothalamic Failure, due to a tumor would
surgery, drug use, chemo/radiotherapy, headache/visual have (+) CT/MRI Findings. For Kallman’s syndrome
changes/seizures (signs of tumor), masses, cyclic hypogastric (amenorrhea + anosmia), individuals would be a giveaway
pain, exercise, stress, weight loss, vasomotor symptoms (hot because they have no sense of smell (anosmia) – because cells
flushes)
of the GnRH and olfactory bulb go together, and so if there is an
• Physical Examination: Height/Weight (BMI),
breast/axillary/pubic hair tanner stage, physical signs, nipple arrest, there would be a problem in olfaction and the
discharge, hirsutism/acne, abdominal masses, pelvic exam: hypothalamus. BOX 3: Also with (+) CT/MRI findings in pituitary
external genitalia, vagina, cervix. such as a tumor, an empty sella, and encephalitis causing
amenorrhea.
VIII. WORK-UP OF PRIMARY AMENORRHEA

Figure 18: Work-up in cases of Breast (+) and Uterus (-). We saw
this in IA and MRKH. How do differentiate? IA has no axillary or
pubic hair, while MRKH has. Other physical findings are similar
e.g. vagina. What would differentiate them is karyotyping and
testosterone levels. AIS has 46XY and high testosterone, but
Figure 16: Algorithm of Primary Amenorrhea Work-up. Pregnancy
MRKH has 46XX and low testosterone.
test is a must! The UTZ will help you determine if the mullerian
system is normal. Then look at the breast and uterus. Why?
Because the breast is an indicator of estrogen secretion,
meaning there is an intact hypothalamic-pituitary-ovarian axis.
The uterus, if present, means the mullerian development is
okay. And then, we classify them to these four.

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Subject Trans Heads: MITCH ABAD | JK | NIKKI

Figure 19: Work-up in cases of Breast (-) and Uterus (-). These
are very rare cases. In fact, she may not even be a female but a
male. These individuals may have no gonads or they cannot
synthesize hormones due to enzyme abnormalities. This is rare,
so forget about it.
Figure 20. Work-up in cases of Breast (+) and Uterus (+)
IX. WORK UP OF SECONDARY AMENORRHEA
Figure 21: Work-up for Secondary Amenorrhea and cases of
Primary Amenorrhea with (+) Breast and (+) Uterus. Remember, if
secondary, think of endocrine problems and acquired anatomical
abnormalities; that’s why the workup is like this, because we are
checking for hormones. Again, rule out pregnancy first! Then
check the outflow tract if it is normal using an UTZ – check for
stenosis, adhesions. Then check the hormone status at each level
of HPO axis (ovary – estrogen; pituitary – prolactin, FSH, TSH;
hypothalamus – influences lower level hormones). (See
appendix for larger image
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Subject Trans Heads: MITCH ABAD | JK | NIKKI
GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)
A. Ways to Determine Estrogen Status
1) ULTRASOUND, midcycle
• Endometrial stripe >4mm = estrogen effect
Figure 22: Ultrasound of uterus. Endometrium is thicker in mid-
cycle. Its growth is dependent on estrogen levels and a thin
endometrium is a sign of low estrogen.
2) PAP SMEAR: Cytohormonal index
• Predominance of superficial cells = estrogen effect
• Predominance of the blue cells = progesterone effect
• Predominance of cells that are very small, and neither blue
or pink = no estrogen effect
Figure 23: Cytohormonal Index. TOP LEFT – superficial
squamous cells -> ESTROGEN STIMULATION; TOP RIGHT –
intermediate cells; BOTTOM LEFT – parabasal cells -> LACK OF
ESTROGEN; and BOTTOM RIGHT – Metaplastic (Basal) Cells
3) PROGESTERONE CHALLENGE TEST
• 10mg of progesterone daily for 5 days
• Simulates the menstrual cycle and, upon cessation, causes
menstruation which will prove estrogen effect. If no bleeding,
no estrogen effect.
• If it does bleed, it means her estrogen is normal and her
ovaries may not be working because of lack of
progesterone, thus there is only a lack in ovulation. But you
still have to check for other causes of anovulation – pituitary
or hypothalamus, adhesions.
4) SERUM ESTRADIOL
• >40pg/mL – normal, <40pg/mL - menopausal
• Positive: bleeding within 14 days from last tablet; (+)
estrogen effect on uterus
• Negative: no bleeding; (-) estrogen or nonresponsive
endometrium
• Simplest but prone to error, since it has a tendency to
fluctuate and you do it randomly.
• Also, it is important to know that you need at least 40pg/mL
of estradiol to menstruate. If >30-40pg/mL, consider either
PCOS or functional hypothyroidism, and so check the UTZ
for abnormalities in the ovary.
• If <30-40pg/mL, check FSH. If high, then it is POI. If low, it
 GYNECOLOGY 3.09: Amenorrhea (Dr.Tongco)

indicates a problem in the hypothalamus or pituitary. And so, o Hormone replacement – to enhance secondary
check CT/MRI for a tumor; if none, then it may be a sexual characteristics, to treat the effects of
hypothalamic pituitary failure. hypoestrogenism (to prevent complications). For
Fertility
EXAMPLE CASES: (refer to algorithm, MEMORIZE
o Ovulation induction agents/gonadotropins
ALGORITHM)
o ART (assisted reproductive technology) – already
1. if estradiol level is low, and the FSH level is high
available in the Philippines
OVARY PROBLEM -> Primary ovarian insufficiency
2. if estrogen is low, FSH is low or normal
XI. Summary
FAILURE OF THE PITUITARY
3. estradiol level is normal, UTS: polycystic ovary
PCOS • Amenorrhea (pathologic) may be primary or secondary.
4. if the ovaries are not polycystic, normal estradiol • Primary amenorrhea (no menarche) is due to genetic or
HYPOTHALAMIC DYSFUNCTION/FAILURE congenital anatomic abnormalities.
• Secondary amenorrhea is due to endocrine disorder or
X. Treatment Guidelines of Amenorrhea acquired anatomic abnormalities.
• Diagnosis and treatment are important because it may be a
sign of a more serious condition and the consequences of
A. Goals of Treatment
amenorrhea may be life-threatening.
• Pregnancy should be ruled out.
• Amenorrhea is just a symptom.
• Diagnostic process is step-wise and logical (minimum of
o Treat the underlying cause, if possible.
tests): involves an investigation of the hypothalamic-pituitary-
o For genetic causes, it is not possible to treat the
ovarian axis and the outflow tract.
underlying cause (such as in the case of IA)
• Goals of treatment: treat underlying cause, enhance fertility,
• Improve fertility
prevent the consequences of the condition
o There is now assisted reproductive technology
• In all individuals with amenorrhea and having a Y
• Menstruation, if desired
chromosome, gonadectomy is recommended to reduce the
o If menstruation is desired give her hormones or pills
risk of gonadoblastoma.
because that is a combination of estrogen and
• The approach to an amenorrheic patient requires a caring
progesterone and it will mimic the normal menstrual
and understanding physician who is able to empathize with
cycle so when you continue that she will just
the patient’s plight and is able to devote time for counseling.
menstruate and prevent all the complications that
can arise from the underlying cause.
o because at times, menstruation is reassuring for a REFERENCES
woman. Even if it is caused by stress, some patients
would still need to see menstruation and so you can 2018 Transes
give them medication that will help them menstruate Dr.Tongco’s Lecture PPT and Recording 2018
(e.g.HRT or progesterone).
• Prevent the complications of the disease GUIDE QUESTIONS

B. Treatment Options From 2018B Trans

• Counseling – this is important but is hard, since there are 1. Which condition will have cryptomenorrhea as a complaint?
instances where patient may actually be male upon A. Mullerian agenesis
investigation, how do you tell that person? Especially when B. Androgen insensitivity syndrome
want to have a family. They would require a lifestyle change. C. Asherman’s syndrome
• Lifestyle change, ideal weight D. Cervical stenosis
o We avoid too much weight or weight loss 2. Which of these conditions will have a positive Progesterone
challenge test?
• Surgery
A. Anovulation
o Gonadal excision: if with Y chromosome (risk of
B. Premature ovarian failure
gonadoblastoma)
C. Cervical atresia
o Vaginal reconstruction for those with problems of
D. Anorexia nervosa
sexual function
3. Which hormonal assay can differentiate mullerian agenesis
o Excision of vaginal septum/hymenotomy for outflow
from androgen insensitivity syndrome?
tract dysfunction
A. LH
• Medical
B. FSH
o Oral contraceptive pills, progesterone for cycle
C. Estradiol
regulation
D. Testosterone
▪ It can accentuate the secondary sexual
characteristics

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4. In which chromosomal complement in a patient with primary non-functional.

amenorrhea is gonadectomy warranted to decrease the risk of
gonadoblastoma?
A. 45XO
B. 46XY
C. 46XX
D. 45XO/46XX
5. In a patient with Asherman’s syndrome, which of these test
results will be correct?
A. Progesterone challenge test: no bleeding
B. Estrogen+Progesterone test: no bleeding
C. Serum FSH = 30 IU/L
D. Serum estradiol = 20 pg/ml
6. Primary amenorrhea in a woman with anosmia is suggestive of
which syndrome?
A. Sheehan’s
B. Kallman’s
C. Swyer’s
D. Rokitansky
7. Which of these findings suggest an adequate estrogen level in
a woman of reproductive age?
A. Thin endometrium on ultrasound
B. Tanner stage 3 breast
C. Parabasal cells on pap smear
D. Copious cervical mucus
8. The finding of a bulging blue membrane on the introital area of
a 12 year old with no menses yet but with cyclic hypogastric pain
is indicative of which condition?
A. Mullerian agenesis
B. Transverse vaginal septum
C. Imperforate hymen
D. Cervical atresia
9. What is the meaning of a positive progesterone challenge test?
A. There is no withdrawal bleeding
B. The patient is anovulatory
C. Something is wrong on the pituitary level
D. Estrogen level is low
10. Which of these conditions will have secondary amenorrhea
due to low GnRH levels?
A. Sheehan’s syndrome
B. Premature ovarian insufficiency
C. PCOS
D. Anorexia nervosa
11. Of the following causes of amenorrhea, which will require
karyotyping for proper diagnosis?
A. Asherman’s syndrome
B. Atrophic endometrium
C. Empty sella syndrome
D. Gonadal dysgenesis
ANSWERS WITH RATIONALE:
1. D – Menstrual blood can’t flow out and will be accumulated in
the uterus over time, causing cryptomenorrhea.
2. A – Progesterone challenge test is an indirect test for
estrogen level, which reflects the ability to ovulate as well.
3. D – Testosterone is high in androgen insensitivity syndrome,
since the patient is genetically a male, but phenotypically a
female due to inability to react to the testosterone.
4. B – The condition is androgen insensitivity syndrome.
Presence of Y chromosome is a risk for gonadoblastoma.
5. B – Asherman’s syndrome is intrauterine adhesion. No matter
how we try to simulate menstruation through giving estrogen
and progesterone, it won’t happen, since the endometrium is
6. B – There is absence of GnRH, hence, no production of FSH
and LH that leads to nonstimulation of follicles and production
of estrogen and progesterone. It is also associated with
anosmia due to absence of olfactory bulb. Swyer’s syndrome
is a pure gonadal dysgenesis with a 46 XY chromosome but
an SRY gene mutation, the patient is externally female with
streak gonads. Mayer-Rokitansky-Kuster-Hauser Syndrome
is due to mullerian dysgenesis that results in underdeveloped
or absent vagina and uterus.
7. D – The other choices are signs of reduced estrogen level.
8. C – Finding of bulging blue membrane
9. B – A positive progesterone challenge test is seen as
withdrawal bleeding, it means that estrogen levels are
adequate, however progesterone levels were low thus
ovulation did not occur (anovulation).
10. D – Sheehan’s syndrome: there is ischemic necrosis of the
pituitary gland, which occurs as a result of excessive
hemorrhage during pregnancy. Low FSH and LH. High
GnRH. Premature ovarian insufficiency: Low estrogen.
HighFSH. HighGnRh. PCOS: amenorrhea due to
hyperandrogenism.
11. D – The rest are secondary causes of amenorrhea, and
genetic testing is not required.
2018 Samplex
90. In which of these patients with amenorrhea is gonadectomy
recommended?
a. Androgen Insensitivity Syndrome
b. Empty Sella syndrome
c. Mullerian Agenesis
d. Turner syndrome
91. What is the best treatment for a 26y/o gymnast w/amenorrhea
of 8 months and a serum estradiol of 20pg/mL?
a. Bromocriptine
b. Estrogen + Progesterone
c. Gonadotropins.
d. Thyroid hormone
92. A 23 y/o had her LMP 9 monthsago. She had no withdrawal
bleeding after a progesterone challenge test. FSH level
iselevated. What is the most likelydiagnosis?
a. Anovulation
b. Craniopharyngioma
c. Pituitary adenoma
d. Primary Ovarian Insufficiency
93. A 14 y/o w/ secondary sexual characteristics complains of
absence of menarche. What is the best test to request at this
point?
a. Estradiol
b. FSH
c. HCG
d. TSH
94. Which test will differentiate Androgen Insensitivity from
Congenital Absence of the uterus?
a. Estradiol
b. FSH
c. Prolactin
d. Testosterone
95. A 30 y/o G1P1 who delivered 10months ago and currently
breastfeeding complains of amenorrhea since her delivery. What
is most likely diagnosis?
a. Hypothalamic dysfunction
b. Hyperprolactinemia
c. Pregnancy
d. Sheehan’s syndrome
96. A 13 y/o w/o menarche complains of cyclic pelvic pain. Breast
and pubic hair are tanner 3. A 10cm cystic hypogastric mass was
palpated. Hymen is intact. What is the most likely diagnosis?

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a. Delayed puberty
b. Ovarian New Growth
c. Pelvic Endometriosis
d. Transverse vaginal septum
97. In which of these syndromes w/ amenorrhea is present?
a. Asherman’s
b. Mayer-Rokitansky-Kuster-Hauser
c. Polycystic Ovarian
d. Swyer
98. A 32-year-old G0 w/ amenorrhea for 1 year has hot flashes
and night sweats. FSH level is elevated. Cytohormonal index
showed predominance of parabasal cells. She wants to
experience monthly periods. What is the best treatment?
a. Estrogen
b. Estrogen and progesterone
c. Recombinant FSH
d. GnRH
99. What is the best treatment for a 31-year-old with milky nipple
discharge, elevated prolactin levels, and a 0.8cm pituitary
adenoma?
a. Dopamine agonist
b. Oral contraceptive pills
c. Surgical extirpation
d. Thyroid hormone
100.What is the most common cause of primary amenorrhea?
a. Delayed puberty
b. Gonadal dysgenesis
c. Mullerian agenesis
d. Outflow tract disorders

ABDCDC DDBAB

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APPENDIX

Work-up for secondary amenorrhea

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