ABNORMAL UTERINE BLEEDING

Susan Maya, MD
Week 24
Educational Objectives:

1. Develop a framework for the evaluation of AUB (abnormal uterine bleeding) in pre-
menopausal women
2. Medically manage hemodynamically stable patients with persistent AUB
3. Determine need for endometrial sampling based on risk factors
4. Evaluate and manage AUB in post-menopausal women

CASE ONE:

A.L. is a 24-year-old female who presents to clinic with complaints of irregular menses.
Since menarche at age 14, her menses have never been regular, and can come anywhere
from every three to six months. Her menses typically last five to seven days and are
sometimes heavy. She is frustrated by the unpredictable nature of her bleeding which has
negatively impacted her quality of life. She is sexually active with one male partner and
uses condoms sometimes but uses no other birth control as she does not believe she can get
pregnant.

Questions:

1. Define abnormal uterine bleeding (AUB). What additional information about the
patient’s menstrual history is needed in order to characterize this patient’s AUB?
Abnormal uterine bleeding is common and affects up to 30% of women of reproductive
age (Liu, 2007). In 2011, the International Federation of Gynecology and Obstetrics
(FIGO) presented updated terminology for abnormal uterine bleeding which the
American College of Obstetrics and Gynecology subsequently endorsed, in order to
replace earlier, less specific terminology such as menorrhagia and metrorrhagia (ACOG,
2012). Abnormal uterine bleeding encompasses a range of symptoms including changes
in menstrual frequency or regularity, volume, or duration that fall outside the normal
population-based 5th to 95th percentiles.

According to FIGO, normal menses occur every 24-38 days (counting from the first day
of bleeding of one cycle to the next), last 4.5 to 8 days, vary less than 20 days over 12
months and involve 5-80 ml total of blood loss per cycle. Bleeding patterns that fall
outside of these definitions are considered AUB (Wouk, 2019; Fraser, 2011). Thus, it is
important to ask about duration of menses, interval between menses, regularity and inter-
menstrual bleeding. Quantifying blood loss in terms of volume is rarely practical.
However, the severity of blood loss can be determined by asking about passing clots and
whether the patient has to change tampons or pads every hour (keeping in mind that you

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 should clarify whether the pads/tampons are soaked through). It is also important to note
the duration of the patient’s symptoms and whether they have been present since
menarche or represent a change from the patient’s typical bleeding pattern.

2. What etiologies are on the differential for AUB? Which are most likely in this
patient?
The first step in the evaluation of AUB in a woman of reproductive age is to determine
pregnancy status, regardless of the patient’s self-reported sexual activity (or lack thereof).
This can be done with a point of care urine human chorionic gonadotropin (HCG) test
($8-38 according to healthcarebluebook.com) or, if this is not available, with a serum
HCG test ($13-65 according to healthcarebluebook.com).

The next step is to confirm that the bleeding is of uterine or vaginal origin, as
occasionally patients can mistake bleeding from other sources (urethra, rectum,
perineum) as coming from a vaginal or uterine source. This can be done by asking about
blood in the stool or on tissue paper when wiping after a bowel movement or frank blood
with urination. During the physical exam, assess for any external labial or perineal
excoriations, ulcerations, fissures, or bleeding from urethral opening, and consider a
digital rectal exam to assess for occult or overt blood in the stool if uncertainty remains
based on history.

Once you have confirmed the patient’s pregnancy status and that the bleeding is likely of
a uterine or vaginal source, you can employ the PALM COEIN mnemonic to assist in
developing a differential. PALM refers to common structural abnormalities while COEIN
refers to nonstructural etiologies (Munro, 2011).

• Polyps – endometrial polyps are a common source of AUB, often causing

intermenstrual bleeding. Occasionally polyps can be visualized extruding from
the cervix on speculum exam, however, they are often exclusively inside the
endometrial cavity and thus not detectable on routine pelvic exam.
• Adenomyosis – refers to endometrial tissue that is located within the myometrium
and can result in painful and heavy menstrual bleeding
• Leiomyoma (fibroids) – an incredibly common cause of AUB which can also
cause pelvic pressure or pain when particularly bulky. Typically, this can lead to
heavy and prolonged bleeding
• Malignancy and hyperplasia – endometrial hyperplasia and endometrial cancers
should always be on the differential, particularly in women over 45 or those with
a history of increased estrogen exposure, including, nulliparity, obesity and
women with untreated PCOS.
• Coagulopathy – should be considered in women with heavy menses since
menarche and/or other symptoms such as easy bruising or epistaxis, a history of
postpartum hemorrhage, surgery-related bleeding or a family history of
coagulopathy
• Ovulatory dysfunction – this category includes common hormonal conditions
such as Polycystic Ovarian Syndrome (PCOS), thyroid disorders,

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 hyperprolactinemia and ovulatory suppression from stress, intense exercise, or
eating disorders
• Endometrial – includes infection such as acute or chronic endometritis
• Iatrogenic – refers to AUB secondary to medications or procedures. Common
culprit medications include combined hormonal contraceptives which can cause
breakthrough bleeding. TCAs cause dopamine antagonism which leads to
increased prolactin secretion and irregular menses and/or anovulation. Typical
and atypical antipsychotics can also raise prolactin levels and in turn cause AUB.
• Not otherwise classified – refers to all other etiologies not already mentioned
including Cesarean scar defects and AV malformations (Wouk, 2019)

While the PALM COEIN mnemonic is helpful for developing a broad differential, other
categorizations of AUB exist, including one based on bleeding type which can be utilized
in conjunction with PALM COEIN to help identify the most likely cause in a given
patient. This categorization is as follows:

• Cyclical (regular) but heavy bleeding: often caused by adenomyosis, fibroids,

copper IUDs, or coagulation disorders
• Non-cyclical/irregular menses: often from ovulatory dysfunction, most often
PCOS, thyroid disorders, medications, stress, or exercise related anovulation
• Intermenstrual bleeding: commonly from endometrial polyps, endometritis
• Post-coital bleeding or spotting: often due to cervical polyps, cervicitis,
malignancy, or ectropion (Kaunitz, 2019)

For this patient with a history of AUB since menarche, she should be asked about
symptoms of hyperandrogenism including acne and hirsutism, and symptoms of hyper- or
hypothyroidism. Her medications should be reviewed, paying particular attention to any
anticoagulants, antidepressants or antipsychotics that could be a culprit. She should also
be questioned about any history of intense exercise, binging/purging behaviors or other
symptoms suggestive of an eating disorder. She should have a complete physical exam
including a thyroid exam, a thorough HEENT exam to look for dental enamel erosion or
parotid swelling, as well as a pelvic exam. The pelvic exam should include an external
vaginal exam looking for signs of external or perineal trauma or lesions that could be
confused for vaginal bleeding. The internal exam should include a speculum exam to
look for cervical lesions or polyps, as well as bimanual exam to determine any focal
masses, uterine enlargement or asymmetry that could suggest fibroids, and an assessment
for cervical motion tenderness. Though unlikely to explain her persistent AUB since
menarche, given her risk factors, she should be offered gonorrhea/chlamydia testing
while the pelvic exam is being done. She should have a TSH, free T4, CBC and ferritin
checked. A prolactin should be checked if she endorses galactorrhea.

3. What is the role of imaging in the evaluation of a pre-menopausal woman with

AUB?
Indications for imaging, typically with transvaginal ultrasound (TVUS), include palpable
uterine or adnexal abnormalities on bimanual exam, or symptoms that persist despite
conservative treatment. A transvaginal ultrasound costs anywhere from $215 to over

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 $570 according to healthcarebluebook.com. There is no consensus on what defines
“persistent” symptoms but many clinicians use a time point of six months. Saline-infused
sonohysterography (SIS) is more sensitive for detecting intracavitary lesions such as
endometrial polyps and should be considered if TVUS is unrevealing
(Wouk, 2019).

CASE ONE CONTINUED:

On further questioning, A.L. reports a history of thick dark hair growth on her upper lip
and in a line between her pubic symphysis and umbilicus, for which she undergoes
frequent waxing. She also endorses a long history of debilitating acne that has been
medication resistant. Her BMI is 34. On exam she is hemodynamically stable with a BP of
124/72 and HR of 70, Temp 98.0. She is well-appearing and overweight with cystic acne on
her face. Her cardiac and lung exam and abdominal exams are benign. She had a point-of-
care urine pregnancy test on check-in which was negative.

4. You suspect Ms. F has PCOS. How do we diagnose PCOS?

Multiple diagnostic criteria have been proposed for the diagnosis of PCOS. The most
commonly used criteria are the 2003 Rotterdam criteria. Patients must have two of the
following three findings:

• Clinical or biochemical evidence of hyperandrogenism - the Ferriman-Gallwey

score can be used to define the degree of hirsutism. However, substantial variation
is seen among different ethnic and racial groups; in addition, physical exam is not
sufficient to determine the presence of hirsutism as many women undergo
procedures to remove unwanted hair. Thus, a patient should be asked specifically
about the presence of excessive hair in a male-pattern distribution. Most
guidelines recommend testing total serum testosterone to confirm the presence of
hyperandrogenism. Keep in mind that if the patient is currently taking combined
hormonal contraception then the testosterone levels will be suppressed and thus
not helpful.
• Polycystic ovaries - TVUS is the primary imaging modality but is NOT necessary
to make a diagnosis of PCOS in all women if they have sufficient evidence of
hyperandrogenism and anovulation. If done, there is currently disagreement about
the definition of polycystic ovaries. The Rotterdam criteria requires 12 or more
cysts in at least one ovary, measuring 2-9 mm each. However, a small 2010 study
found that 32% of premenopausal women with normal cycles meet this criterion
(and over 50% of study participants under age 30), thus calling into question
whether a higher cutoff should be used. (Johnstone, 2010)
• Oligo- or anovulation - based on clinical history

Confirmation of the diagnosis requires excluding other likely causes of AUB and
hyperandrogenism. In particular, non-classical congenital adrenal hyperplasia (NCCAH)

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 should be ruled out by checking a 17-hydroxyprogesterone (ideally at 8AM). Though less
common, NCCAH is often mistaken for PCOS as features include AUB and
hyperandrogenism. Women with severe or new, rapid onset of hyperandrogenism should
be evaluated for androgen secreting tumors and this would be an indication to check a
DHEAS level in addition to serum testosterone.

Editor’s Note: For more on PCOS, please see Week 17 in the 10th edition, Volume 4,
2020.

CASE TWO:

M.A. is a 47-year-old female with a history of obesity, tobacco use disorder, type 2 diabetes
mellitus, depression, and chronic low back pain. She presents with a complaint of heavy
menses for the past six months that have been occurring approximately every two weeks.
She denies hot flashes or vaginal dryness. Her LMP was two weeks ago and she is still
bleeding. She is not currently sexually active. She is G2P2 (both normal spontaneous
vaginal deliveries). Her physical exam is unremarkable, and her pelvic exam reveals a
normal appearing multiparous cervix without lesions or discharge and on bimanual exam
her uterus has a normal size and contour and she does not have any adnexal tenderness.
She has a small amount of blood in the vaginal vault but no clots. Urine pregnancy testing
is negative.

5. In addition to testing for gonorrhea and chlamydia, what other testing should be
done?
A CBC and ferritin should be checked to look for iron deficiency anemia, which, if
present, should be corrected with oral ferrous sulfate every other day (thought to yield
superior absorption when compared to daily supplementation) if the patient can tolerate.

This patient who has multiple risk factors for endometrial cancer (age > 45, obesity,
DM), should be referred for endometrial sampling to rule out endometrial cancer or
hyperplasia. While all women eventually develop anovulatory cycles and AUB as part of
the menopausal transition, this typically results in lengthened cycles and lighter or missed
periods. This patient’s persistent heavy intermenstrual bleeding, especially in the absence
of vasomotor symptoms to suggest the menopausal transition, is concerning and should
prompt referral to gynecology. ACOG guidelines recommend that any patient over 45
with AUB be referred for endometrial sampling but do not give guidance on whether to
exclude those who are suspected to be in the perimenopausal transition. In clinical
practice, those with AUB that clearly fits a pattern of menopausal transition
(characterized by lengthening cycles and missed cycles), especially if associated with
other systemic symptoms, do not require further evaluation whereas those with AUB
consisting of heavier bleeding or more frequent bleeding episodes should be referred. If
there is any uncertainty over whether the AUB represents the menopausal transition, then
consultation with a gynecologist can be helpful. Any patient with endometrial cancer risk

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 factors and persistent AUB without an identifiable cause should be referred for
endometrial sampling. Common risk factors for endometrial cancer include obesity,
nulliparity, a history of PCOS—all of which increase estrogen exposure—as well as type
2 diabetes mellitus (unclear if related to associated obesity or a separate mechanism) and
atypical glandular cells on cervical cytology (a marker for premalignant disease of the
cervix and endometrium). Relative risks for various risk factors for endometrial cancer
are shown in Table 3 of the primary source (Wouk, 2019). Typically, in-office
endometrial biopsy (EMBx) is the first step ($531 to over $1600 according to
healthcarebluebook.com). If symptoms persist despite a normal or inconclusive biopsy
then hysteroscopy with dilation and curettage may be necessary ($2,293 to more than
$6,500 according to healthcarebluebook.com).

CASE TWO CONTINUED:

M.A. undergoes EMBx which is negative for hyperplasia or malignancy. She continues to
have bothersome AUB and undergoes a TVUS which shows two large fibroids and a 5 mm
endometrial stripe, with normal appearing ovaries.

6. Is the size of the endometrial stripe helpful in this patient?

No, in pre-menopausal and peri-menopausal women the endometrial stripe measurement
is NOT useful as it can vary based on timing within the menstrual cycle.

7. You suspect her AUB is related to fibroids. What treatments are available for
symptomatic fibroids?
There are a variety of treatment options for fibroids depending on the patient’s symptom
severity and whether the patient desires fertility preservation. Management of
symptomatic fibroids typically begins with oral NSAIDs or combined oral contraceptive
pills (COCP), both of which can help reduce menstrual blood loss and decrease pain. One
mechanism by which NSAIDs work is decreasing prostaglandin production leading to
vasoconstriction in the endometrium. With regards to COCPs, keep in mind the absolute
contraindications to use include, age > 35 and smoking >15 cigarettes a day (therefore, in
this patient, we would need to quantify her tobacco use); migraines with aura; early
postpartum period; established CAD or history of stroke; and severe hypertension,
>160/100. (Please see U.S. Medical Eligibility Criteria for Contraceptive Use, available
as an application for smartphones, for further information.) For women with fibroids who
do not desire pregnancy, the levonorgestrel-releasing intrauterine device (Mirena IUD)
results in a 91% reduction in menstrual blood loss compared with 13% reduction with
COCPs (De La Cruz, 2017). IUD placement costs anywhere from $155 to more than
$483, not including the cost of the device (healthcarebluebook.com). A Mirena IUD costs
$1,005 (wwwdrugs.com). Of note, some insurances will pay for the device but not the
insertion or removal.
Tranexamic acid, a non-hormonal anti-fibrinolytic agent that blocks the conversion of
plasminogen to plasmin, can be used during bleeding episodes and is safe in women

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 attempting to conceive but is contraindicated in women at increased risk of thrombosis
(for example, our patient, M.A., who is 47, obese, and a smoker) and is typically only
recommended for short-term use. Other agents including gonadotropin releasing
hormone (GnRH) agonists such as leuprolide and selective progesterone receptor
modulators are sometimes used by gynecologists pre-operatively. A variety of
interventional and surgical procedures are also available including myomectomy
(removal of uterine leiomyomas, often done laparoscopically), which can be fertility
preserving, and uterine artery embolization which may decrease future fertility rates.
Hysterectomy can be offered for symptomatic patients who are treatment-resistant and do
not desire future pregnancies.

8. If M.A. had a normal ultrasound without fibroids, and negative endometrial biopsy
and sonohysterogram, how would you manage her ongoing AUB?
Symptomatic management of persistent AUB without a cause, for which endometrial
cancer has been ruled out, has a variety of treatment options. Medical management with
the Mirena IUD is most effective in decreasing bleeding and results in a blood loss
reduction of 71% to 95% (Matteson, 2013). For women with AUB due to ovulatory
dysfunction or presumed endometrial causes, COCPs (typically with 35 mcg of ethinyl
estradiol) lead to a 35% to 69% reduction in blood loss and may also improve menstrual
regularity. COCPs (typically low dose, i.e., 20 mcg ethinyl estradiol) can be particularly
useful for women who are peri-menopausal and desire menstrual regularity and can be
continued until age 50 or 51 when most women are post-menopausal. Depo-Provera is
another option for women who do not desire pregnancy, with half of women becoming
amenorrhoeic after 12 months of use, however it can often cause irregular bleeding
initially. Lastly, continuous oral progesterone with norethindrone 5 mg daily is also an
option, especially for women who have contraindications to estrogen. After achieving
control of AUB, the dose is typically gradually tapered down and then stopped. There is
no high-quality data on efficacy of cyclic progesterone regimens versus continuous
dosing. The primary care provider may wish to consult with a gynecologist in this case.
Of note, the progestin-only pill, which contains 0.35 mg norethindrone, has not been
studied for treatment of AUB (Wouk, 2019).

CASE THREE:

S. R. is a 62-year-old female with a history of right knee osteoarthritis, osteopenia, and

hyperlipidemia. She presents with one episode of light vaginal bleeding over the past month
and is concerned. Her LMP was 10 years ago.

9. How does the differential differ in a post-menopausal woman? What additional

history would you like to obtain?
Any post-menopausal women who presents with vaginal bleeding should be considered
to have endometrial cancer until proven otherwise.

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
 In post-menopausal women, initial evaluation of first episode post-menopausal vaginal
bleeding can be done with TVUS for women without additional risk factors for
endometrial cancer (see above discussion for list) and not on hormone replacement
therapy. If the endometrial stripe is less than or equal to 4 mm AND the endometrium is
homogenous and is adequately visualized, then endometrial hyperplasia or malignancy
can reasonably be excluded. A thin endometrial stripe has a 99% negative predictive
value for endometrial cancer. Alternatively, the patient can be directly referred for
endometrial biopsy. TVUS can also be done after endometrial sampling if the sample was
insufficient or the patient was unable to tolerate the procedure. Regardless of endometrial
thickness, postmenopausal patients with persistent vaginal bleeding should be referred for
endometrial sampling. Women with additional risk factors for endometrial cancer should
always be directly referred for endometrial sampling (ACOG Committee, 2018).

Once endometrial cancer has been effectively ruled out, alternative diagnoses can be
considered including polyps, fibroids (less prevalent than in pre-menopausal women but
still a possibility), and endometrial or vaginal atrophy.

CASE THREE CONTINUED:

S.R. is referred to gynecology and undergoes endometrial biopsy which shows atrophic
endometrium without hyperplasia and the sample was sufficient for evaluation. She
returns to you for follow-up and denies further bleeding episodes. On further questioning
she denies hot flashes but endorses pain with intercourse and urinary frequency with
frequent UTIs over the past three years. On exam, the patient has a thinned labia with
fusion of the clitoral hood. She has a narrowed vaginal introitus and moderate pain with
insertion of the small size speculum. She has loss of vaginal ruggae and the mucosa appears
pale and easily friable.

10. You suspect her isolated bleeding episode is related to vaginal atrophy and
genitourinary syndrome of menopause. How can you treat her genitourinary
syndrome of menopause?
This patient’s isolated light bleeding may be of vaginal origin related to friable mucosa
which results from the loss of estrogen during menopause. For patients who primarily
have symptoms of vaginal atrophy including dyspareunia, dryness or bleeding, initial
treatment typically involves vaginal lubricants and moisturizers though there is little
evidence on efficacy. Lubricants can be used prior to intercourse whereas moisturizers
are typically used two to three times weekly regardless of sexual activity. A variety of
over the counter formulations are available. For patients with severe symptoms or those
who are unresponsive to initial therapy, vaginal estrogen treatment can be used, provided
the patient has been ruled out for endometrial cancer using the approach explained
above. Topical estrogen comes in a variety of formulations including a gel, ring, and
vaginal suppository. Formulation can be selected based on patient preference, cost and
insurance coverage. The vaginal estrogen gel can cost around $125 for a 90-day supply,

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
compared with about $14 for the vaginal estrogen tablet, but this varies based on
insurance coverage (goodrx.com).

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
Primary Reference:

1. Wouk N, Helton M. Abnormal Uterine Bleeding in Premenopausal Women. Am Fam

Physician. 2019 Apr 1;99(7)435-43. https://www.aafp.org/afp/2019/0401/p435.pdf

Additional References:

1. Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health‐
related quality of life, work impairment, and health‐care costs and utilization in abnormal
uterine bleeding. Value Health. 2007;10:183–94.
2. American College of Obstetricians and Gynecologists Practice Bulletin. Diagnosis of
abnormal uterine bleeding in reproductive-aged women, No.128. Obstet Gynecol.
2012;120(7):197-206.
3. Kaunitz AM. Abnormal uterine bleeding in reproductive age women. JAMA.
2019;321(21:)2126-7.
4. De La Cruz MS, Buchanan EM. Uterine fibroids: Diagnosis and treatment. Am Fam.
Physician. 2017;95(2)100-7.
5. Matteson KA, Rahn DD, Wheeler TL 2nd, Casiano E, Siddiqui NY, Harvie HS, Mamik
MM, Balk EM, Sung VW; Society of Gynecologic Surgeons Systematic Review Group.
Nonsurgical management of heavy menstrual bleeding; a systematic review. Obstet
Gynecol. 2013 Mar;121(3);632-43.
6. ACOG Committee Opinion No. 734: The role of transvaginal ultrasonography in
evaluating the endometrium of women with postmenopausal bleeding. Obstet and
Gynecol. 2018;131(5)e124-9.
7. Johnstone EB, Rosen MP, Neril R, Trevithick D, Sternfeld B, Murphy R, Addauan-
Andersen C, McConnell D, Pera RR, Cedars MI. The polycystic ovary post-rotterdam: a
common, age-dependent finding in ovulatory women without metabolic significance.
J Clin Endocrinol Metab. 2010;95(11):4965-72.
8. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on
terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod
Med. 2011;29(5):389.
9. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-
COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive
age. Int J Gynaecol Obstet. 2011;113(1):3–13.

Susan Maya, MD is an Assistant Professor of General Internal Medicine at Yale. She is a

primary care physician and clinician educator at the West Haven Veteran’s Affairs Hospital
and also works as a designated women’s health provider in the VA Women’s Clinic. Her
clinical interests include women’s health and care of transgender and gender non-conforming
patients. She lives in New Haven with her husband and their pug puppy.

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
Knowledge Questions:

1. A 24-year-old female presents with one year of infrequent and irregular menses.
Menarche was at age 13 and she had normal menses approximately every 30 days
with five to seven days of bleeding until this past year. Her past medical history
includes bipolar disorder, GERD, and migraines. Her medications include
pantoprazole 20 mg daily, risperidone 2 mg BID and amitriptyline 10 mg QHS.
Which medication(s) might be contributing to her AUB?

a. Pantoprazole
b. Risperdal
c. Amitriptyline
d. Risperdal or Amitriptyline

2. Which of the following patients should be referred for endometrial sampling?

a. A 55-year-old obese woman who states her LMP was three years ago and presents
with another “period” last month
b. A 34-year-old woman with obesity, hirsutism, and acne who reports a long-
standing history of irregular menses
c. A 49-year-old woman with a normal BMI and no past medical history who
reports a new change in her menses. Her menses now occur every 45-60 days and
they seem to be lighter than normal

3. A 35-year-old woman with persistent abnormal uterine bleeding and heavy menses
despite normal TVUS and EMBx and hormonal testing wishes for non-surgical
treatment. Which option is most likely to result in the largest decrease in her
bleeding episodes?

a. Naproxen 500 mg BID during bleeding days

b. Mirena IUD
c. Combined hormonal contraceptive pills

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020
Answers:

1. d Both amitriptyline, a TCA, and risperidone, an antipsychotic, can lead to

hyperprolactinemia resulting in anovulation and AUB.
Risperidone is particularly high risk for this effect.
2. a A woman who is post-menopausal for over a year and reports a recent bleeding
episode should be considered to have post-menopausal vaginal bleeding and should
be referred for endometrial sampling, especially if she has other risk factors for
endometrial cancer such as obesity. See above discussion for who might be a
candidate for TVUS as an initial step. B is incorrect because this patient likely has
PCOS and should be evaluated for this first. C is incorrect because the woman has no
other risk factors for endometrial cancer and more likely has changes associated with
perimenopause. However, this example is not clear cut and consultation with a
gynecologist may be advised.
3. b Mirena IUD has been shown to lead to the largest decrease in bleeding amount
compared with COCPs and Depo-Provera injections. NSAIDs such as naproxen have
a modest impact on bleeding.

Abnormal Uterine Bleeding. Yale Office-based Medicine Curriculum, Tenth Edition, Volume 5, 2020