CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 55, Number 3, 635–650
Office Diagnosis and
Management of
Abnormal Uterine
Bleeding
MING C. TSAI, MD and STEVEN R. GOLDSTEIN, MD
Department of Obstetrics and Gynecology, New York University
School of Medicine, New York, New York
Abstract: Abnormal uterine bleeding is one of the most
common presenting complaints encountered in a gyne-
cologist’s office or primary care setting. The availability of
diagnostic tools, such as ultrasound, endometrial sam-
pling, and diagnostic hysteroscopy has made it possible to
promptly diagnose and treat an increasing number of
menstrual disorders in an office setting. The incorpora-
tion of newer medical therapies: antifibrinolytic drugs,
shorter hormone-free interval oral contraceptive pills, and
levonorgestrel inserts along with office minimally invasive
treatments operative hysteroscopy and endometrial abla-
tions have proven to be powerful therapeutic arsenals to
provide short-term relief of abnormal uterine bleeding,
and potentially, avoiding or delaying the hysterectomy.
Key words: abnormal uterine bleeding, conservative
treatment, office diagnosis and management, men-
strual disorder, minimally invasive procedure, heavy
menstrual bleeding
Introduction
Disorders of the menstrual cycle are
a common problem in ambulatory
Correspondence: Ming C. Tsai, MD, Department of Ob-
stetrics and Gynecology, New York University School of
Medicine, New York, NY. E-mail: ming.tsai@nyumc.org
S.R.G. serves as consultant for Cook ObGyn and
Phillips Ultrasound. He is on Gyn Advisory board of
Shionogi, Bayer and Amgen and Speaker Bureau for
Warner Chilcott and Amgen. The other author declares
that he has nothing to disclose.
CLINICAL OBSTETRICS AND GYNECOLOGY
r 2012, Lippincott Williams & Wilkins
medicine, accounting for up to 30% of
outpatient visits to gynecologists. Abnor-
mal uterine bleeding (AUB) describes
bleeding that is excessive or occurs outside
of normal cyclic menstruation and ac-
counts for two thirds of hysterectomies.
Apart from its social inconvenience, in
many cases, AUB can result in anemia,
impaired quality of life, and psychological
distress. The role of the clinician in a
patient who presents with bleeding is
two-fold: first, to exclude endometrial
carcinoma in women older than 35 years
and second, to identify the source of
bleeding so it can be stopped or managed.
Because of its broad range of differential
diagnosis, the diagnosis of AUB can be
quite challenging; despite a detailed his-
tory, various blood tests, and a thorough
pelvic examination, often involving trans-
vaginal ultrasonography (TVS), the cause
of the bleeding is established in only 50%
to 60% of the cases. Deciding on the best
medical therapy for AUB can be difficult
because of the numerous treatment op-
tions available and complicated by a lack
of standardized treatment protocol.
/ VOLUME 55 / NUMBER 3 / SEPTEMBER 2012
www.clinicalobgyn.com | 635
636 Tsai and Goldstein
Definition
AUB is a nonspecific term that describes a
broad range of clinical presentations. It is
best defined as bleeding that is excessive or
occurs outside of normal cyclic menstrua-
tion. It can have a variety of menstrual
patterns, which, by clinical experience, have
yielded empirical definitions (Table 1).
There is an inconsistency in the nomencla-
ture used to describe AUB, and does not
provide necessary information on etiology
of bleeding, coexisting uterine pathology,
or underlying systemic diseases. The Inter-
national Federation of Gynecology and
Obstetrics working group on menstrual
disorders has recently developed a classifi-
cation system (PALM-COEIN) for causes
of AUB in nongravid women of reproduc-
tive age.1 There are 9 main categories,
which are arranged according to the acro-
nym PALM-COEIN: polyp; adenomyosis;
leiomyoma; malignancy and hyperplasia;
coagulopathy; ovulatory dysfunction; endo-
metrial; iatrogenic; and not yet classified.
According to the proposed classification
system, nonspecific term such as dysfunc-
tional uterine bleeding (DUB) should be
abandoned to favor a more specific etiology
such as ovulatory dysfunction. These termi-
nologies are, however, not yet endorsed by
American Congress of Obstetricians and
Gynecologists. It is important to emphasize
that although menstrual blood loss can be
TABLE 1. Definition of Abnormal Uterine
Bleeding
Intermenstrual Bleeding between menstrual
bleeding cycles
Metrorrhagia Irregular bleeding
Menorrhagia Excessive bleeding at
regular intervals
Polymenorrhea Menstrual cycle interval
<21 d
Oligomenorrhea Menstrual cycle interval
>35 d
Menometrorrhagia Excessive bleeding at
irregular interval
Postmenopausal Genital tract bleeding
bleeding occurring >12 months after
the last menstrual period
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objectively measured with an alkaline hem-
atin test, in clinical practice, the diagnosis of
type of menstrual disorder often relies on
patient perception of what represents their
own ‘‘normal’’ or ‘‘abnormal’’ bleeding in
terms of quantity, duration, and frequency,
and more importantly, whether it is affect-
ing the patient’s quality of life.
Pathophysiology Underlying
Abnormal Endometrial
Bleeding
In contrast to normal menstrual cycle,
AUB reflects disruption at any point of
physiological control of hypothalamic-
pituitary-gonadal axis. Impaired endome-
trial hemostasis and vasculature fragility as
the result of aberrant angiogenesis consti-
tute 2 principal causes of abnormal endo-
metrial bleeding.1 Anovulatory bleeding is
one of the most common causes of AUB
especially in early and late reproductive
ages. Unlike the uniform synchronized
sloughing and bleeding that occurs with
cyclic estrogen and progesterone stimula-
tion, endometrial shedding during contin-
uous estrogen stimulation is irregular and
incomplete resulting in the potential for
irregular and prolonged menstrual flow.
The precise mechanism underlying bleed-
ing in leiomyoma and endometrial polyps
remains elusive. The fragile abnormal an-
giogenesis with large-caliber vessels present
in stretched and thin endometrium over
submucosal fibroids can be a cause of
bleeding and denuded endometrium pre-
venting adequate hemostasis. Endometrial
polyps can result in bleeding mainly be-
cause of vascular fragility and endometrial
erosion secondary to friction of the pro-
truding mass.
Differential Diagnosis
One of the most challenging aspects of
diagnosis and treatment of AUB is the
wide array of differential diagnose for the

TABLE 2. Differential Diagnosis of Abnormal Uterine Bleeding According to Age Groups
Neonate
Estrogen withdrawal
Premenarchal
Foreign body
Trauma, sexual abuse
Infection
Urethral prolapse
Ovarian and vaginal tumor
Precocious puberty
Early postmenarchal
Anovulation
Bleeding diathesis
Stress
Pregnancy
Infection
PCOS
PCOS indicates polycystic ovarian syndrome.
same bleeding symptom (Table 2). Ruling
out nongynecologic source of bleeding
such as urethral or rectal bleeding is man-
datory. The likely diagnosis can be sus-
pected by history, thorough physical
examination, the patient’s age, and repro-
ductive status. Although considerable
overlap in etiologies may occur, there
are important differences regarding dif-
ferential diagnosis, evaluation, and man-
agement in each group.
NEONATE AND PREPUBERTAL GIRLS
The high estrogen level during pregnancy
can induce stimulation of intrauterine
endometrial proliferation, resulting in
uterine bleeding in female neonate after
birth. Such bleeding is usually self-limited
and characterized by spotting. When vag-
inal bleeding occurs in prepubertal pa-
tients, 74% of the bleeding originates
from the lower genital tract. Vulvovagi-
nitis is the most common etiology, fol-
lowed by urethral prolapse, trauma, and
foreign body. Malignant lesions in the
lower genital tract, such as adenocarcino-
ma, endodermal sinus tumor of the vagi-
na, and sarcoma botryoides, will usually
bleed early in their development, in
Office Management of Menstrual Disorder 637
Reproductive Year
Anovulation
Pregnancy
Cancer
Polyps, fibroid, adenomyosis
Infection
Endocrine dysfunction (PCOS, thyroid, pituitary adenoma)
Bleeding diasthesis
Medication-related (OCP, antipsychotic)
Perimenopausal
Anovulation
Polyps, fibroid, adenomyosis
Cancer
Menopause
Atrophy
Cancer
Estrogen replacement therapy
contrast to benign lesions that seldom
cause bleeding. Bright red spotting should
alert the health care provider about the
possibility of malignancy as they are usu-
ally not palpable by rectal examination
and not detected by vaginal smear cytol-
ogy. The remaining 26% of prepubertal
bleeding is uterine in origin and attributed
to some form of precocious puberty, with
a hormone producing ovarian tumor is
the underlying cause in majority of the
cases.
ADOLESCENTS
Anovulation should be considered as the
most likely diagnosis of AUB in most
adolescents especially those close to me-
narche. The etiology is related to imma-
turity of hypothalamic-pituitary axis,
which results in unpredictable anovula-
tory cycles. It is estimated that up to 85%
of menstrual cycles are anovulatory in the
first year after menarche and 56% of
menstrual cycles are ovulatory 4 years
after the menarche. In case of oligome-
norrhea or amenorrhea, pregnancy
should be suspected. Although anovula-
tion is the most common cause, practi-
tioners should be alerted that 10% to 47%
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638 Tsai and Goldstein
of adolescents with heavy menstrual
bleeding may have an underlying bleeding
disorder. Von Willebrand disease and
platelet dysfunction account for the
most common hematologic disorders
in this age group. Other bleeding dyscra-
sias include Factor XI deficiency, hemo-
phillia carrier states, and rare factor
deficiencies.
REPRODUCTIVE AGE WOMEN
When a pregnancy event has been ex-
cluded, the most likely cause of bleeding
in reproductive age women is DUB. As
women age, organic pathologies such as
leiomyoma, polyps, adenomyosis, endo-
metrial hyperplasias, and even frank car-
cinoma become more likely. Fibroids,
along with intracavitary lesions, distort-
ing the uterine cavity are the most com-
mon etiology of organic cause of AUB in
this age group. Focal intracavitary lesions
maybe present in up to 56% of premeno-
pausal women presenting with AUB re-
fractory to medical treatment. Chronic
medical problems such as disorders of
liver, kidney, thyroid or adrenal glands,
or other medical problems that can affect
the production and metabolism of estro-
gen, progesterone, and prolactin can re-
sult in abnormal bleeding. Emotional or
physical stress, and significant changes in
body weight, may disrupt the release of
follicle stimulation hormone (FSH) and
luteinizing hormone (LH) and prevent
ovulation.
PERIMENOPAUSAL AND
POSTMENOPAUSAL WOMEN
For those perimenopausal women pre-
senting with menorrhagia and metrorrha-
gia, organic pathology and endometrial
cancer should be mandatorily ruled out.
Eventual worsening of bleeding symp-
toms can sometimes be explained by the
coexistence of anovulatory cycles and or-
ganic pathology.
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Any vaginal bleeding in postmenopausal
patients should be considered abnormal
until proven otherwise. Although an atro-
phic endometrium is the most likely cause
of postmenopausal bleeding, it is imperative
to rule out endometrial cancer. Hormonal
therapy (HT) using combined estrogen and
progesterone therapy given continuously
without break is associated with a variable
incidence of unscheduled spotting and
bleeding, with an incidence estimated to
be approximately 40%. Health care pro-
viders should use their experience and the
degree of patient concern to determine
when and to what extent endometrial eval-
uation is necessary.
Diagnosis and Initial Work-up
Although many authors and experts have
advocated the need to establish protocols
for management of AUB, in our opinion,
such an evaluation should be individual-
ized and will be based on the physician’s
clinical judgment as to the underlying
cause of the bleeding. If AUB is not severe
and does not require emergent interven-
tion, evaluation should begin with a care-
ful medical history and thorough physical
examination. The history should carefully
inquire about the pattern, quantity, and
extent of recent bleeding. To quantify
blood loss, it is useful to ask the patient
how many pads or tampons she uses each
period (<21 would be normal), how often
she has to change pads (every 3 h is usual).
Although quantification of blood loss is
important to establish the diagnosis of
menorrhagia by textbook definition,
nonetheless, in clinical practice, it is often
a woman’s subjective perception of what
is considered as a ‘‘normal menstrual
period’’ that determines the diagnosis of
AUB. The temporal relationship of pa-
tient complaints and other information
from her history may also provide valua-
ble clinical information. A single episode
of AUB in premenopausal women favors
expectant management in contrast to
 Office Management of Menstrual Disorder
persistent abnormal bleeding for several
months, which mandates investigation.
For example, a 30-year-old woman with
oligoamenorrheic cycles found to be
obese and having signs of virilization on
physical examination is suggestive of pol-
ycystic ovarian syndrome (PCOS) in con-
trast, a similar aged athletic woman with
an identical menstrual pattern but low
body mass index the diagnosis would
more likely be hypothalamic amenorrhea.
Sexual history, trauma, and symptoms of
infection or systemic disease should be
explored as possible underlying etiology
for the uterine bleeding. The patient
should be asked about medication usage
both past and present. A thorough bleeding
history may yield important clues about
bleeding disorders. Bleeding symptoms that
are highly predictive of a bleeding disorder
is prolonged bleeding after wounds, easy
bruising, bleeding with minor injury, his-
tory of frequent and/or difficult to control
nose bleeding, bleeding after tooth extrac-
tion, postpartum hemorrhage, and postop-
erative bleeding. As these disorders are
inherited, family history of menorrhagia
or the above symptoms should be elicited
as well. In addition, health care providers
should also be attentive to the clinical signs
of anemia, which can be manifest with:
fatigue, exercise-induced fatigue, shortness
of breath, syncope, inability to perform
daily activity, or congestive heart failure in
severe cases.
The physical examination may also elicit
clues of bleeding etiologies. It should begin
with careful inspection of the lower genital
tract looking for lacerations, vulvar or vag-
inal pathology, and cervical lesions or pol-
yps. The inspection serves the purpose to
confirm the site of bleeding, whether it is
uterine in origin or other nongynecologic
source of bleeding that may prompt referral
to appropriate specialists. Bimanual pelvic
examination helps to detect uterine enlarge-
ment from uterine fibroids, adenomyosis,
or hormone producing ovarian tumors as
possible underlying causes of bleeding.
639
LABORATORY TESTING
Laboratory investigation includes preg-
nancy testing in all patients of reproduc-
tive age. A complete blood count provides
a measure of blood loss and platelet ad-
equacy. Cervical cultures and a Pap smear
are appropriate initial steps to evaluate
for the presence of sexually transmitted
diseases or cervical dysplasia. In patients
presenting with irregular periods, ruling
out systemic diseases such as hypothyr-
oidism and abnormal production of pro-
lactin is mandatory. Ideally, fasting serum
prolactin should be obtained and re-
peated if elevated on first sample. Ele-
vated levels of prolactin, in the absence
of pregnancy, are often idiopathic but
may indicate hypothyroidism or a tumor
of the pituitary gland and cause irregular
or absent ovulation. Evaluation with
FSH, LH, and estradiol level will help to
identify the etiologic dysfunction along
the hypothalamic-pituitary-gonadal axis.
FSH/LH/estradiol can be assessed on day
3 of the menstrual cycle when menses are
regular but any day of the cycle when
menstrual cycles are irregular. Increased
levels of FSH and LH and low serum
estradiol are consistent with low ovarian
reserve or primary ovarian failure. Low
levels of FSH and LH are consistent with
secondary ovarian dysfunction because of
a pituitary or hypothalamic causes. High
levels of FSH and LH with the develop-
ment of secondary sex characteristics at
an unusually young age are an indication
of precocious puberty. LH/FSH ratio
greater than 2:1 or 3:1 may be helpful in
the diagnostic for PCOS. FSH results can
be increased with use of cimetidine, clo-
miphene, digitalis, and levodopa. FSH
results can decrease with oral contracep-
tives, phenothiazines, and HT. If symp-
toms of virilization are not evident in
suspected PCOS patients, androgen ex-
cess can be tested by measuring total and
free testosterone levels or a free androgen
index. An elevated free testosterone level
is a sensitive indicator of androgen excess.
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640 Tsai and Goldstein
If the index of suspicion is high for Von
Willebrand disease, consultation with a
hematologist is recommended.
ENDOMETRIAL SAMPLING
Although the incidence of endometrial
cancer in patients with AUB is relatively
low, the possibility of endometrial hyper-
plasia or malignancy should be consid-
ered in patients presenting with irregular
bleeding. Just which patients should
undergo further assessment of the endo-
metrium is problematic in premenopausal
women. Metrorrhagia, persistent spot-
ting, or bleeding should be more concern-
ing as compared with menorrhagia in the
setting of regular cycle. In fact, the Amer-
ican College of Obstetrician and Gynecol-
ogists Practice Bulletin No. 142 states:
‘‘There is a distinct increase in the inci-
dence of endometrial carcinoma from
ages 30-34 years (2.3/100,000 in 1995) to
ages 35-39 (6.1/100,000 in 1995). There-
fore based on age alone, endometrial as-
sessment to exclude cancer is indicated in
any woman older than 35 years who is
suspected of having anovulatory uterine
bleeding.’’ In addition, women younger
than 35 years who have sufficient risk
factors (eg, morbid obesity, polycystic
ovary syndrome) may also require endo-
metrial sampling. Women with postme-
nopausal bleeding may be evaluated
initially with either TVS or endometrial
biopsy. Biopsy is not recommended in
postmenopausal bleeding with endometrial
thickness of r4 mm as the negative predic-
tive value for endometrial cancer approx-
imates 99%. Women using tamoxifen and
presenting with any abnormal vaginal
bleeding, bloody vaginal discharge, stain-
ing, or spotting should be investigated to
exclude endometrial cancer. In asympto-
matic women using tamoxifen, screening
for endometrial cancer with routine trans-
vaginal ultrasound or endometrial sam-
pling or both, have not been shown to be
effective.
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The accuracy of pipelle biopsy to detect
endometrial malignancy varied widely ac-
cording to different studies. Stovall et al,3
evaluated 40 women with known carcino-
ma, pipelle biopsy performed in the clinic
the week before hysterectomy yielded
cancer in 39. Hence, they reported sensi-
tivity of 97.5%. Subsequent reports to
reproduce Stovall’s study on patients with
known carcinoma demonstrated lower sen-
sitivities ranging as low as 67%,4 83%,5
and 92% being reported.6 In another pro-
spective study by Guido and colleagues,
where pipelle endometrial samplings were
performed before hysterectomy for endo-
metrial cancer staging, the pipelle biopsy
was adequate for analysis in 63 of 65
patients (97%). Malignancy was detected
by biopsy in 54 of 65 patients, for a sensi-
tivity of 83 ± 5% (mean ± SD). Of the 11
patients with false-negative results, 5 had
tumors present in only an endometrial
polyp. Three of the 11 patients had disease
localized to <5% of the surface area of the
endometrium.5 The possible explanation
for the limitation of pipelle endometrial
biopsy is because many endometrial path-
ologies including cancer are focal lesions.
In 1 study, pipelle sampled an average of
4% of the endometrial surface area (range
0% to 12%).7 Recent evidence has sug-
gested saline-infusion sonography (SIS)-
guided endometrial sampling is superior
to blind endometrial biopsy in diagnosing
endometrial pathology in perimenopausal
and postmenopausal women with AUB.8
Pipelle biopsy is excellent for detecting
global process; a negative biopsy in light
of persistent vaginal bleeding should
prompt further endometrial evaluation be-
cause a focal endometrial lesion can be
missed.
OFFICE HYSTEROSCOPY
The availability of small-diameter hys-
teroscopes and small operative instru-
ments has increased the advantages of
this procedure, enabling hysteroscopy to
 Office Management of Menstrual Disorder
be performed in an awake patient in an
office setting. As intracavitary lesions are
common in women with complaints of
AUB, hysteroscopy constitutes an impor-
tant diagnostic tool. Lasmar and col-
leagues, retrospectively examined 4054
patients with AUB who were evaluated
with hysteroscopy, endometrial polyps
were the most frequent hysteroscopic
finding, accounting for 33.9% of the
cases. Normal uterine cavity and cervical
canal were found in 20.1%. Submucous
fibroids were diagnosed in 7.5% of wom-
en. Normal endometrium was the most
frequent histologic diagnosis, accounting
for 46.6% of cases. Endometrial hyper-
plasia was diagnosed in 15.1% and endo-
metrial cancer in 2.6%.9
Outpatient hysteroscopy has been in-
creasingly utilized for treatment at the
time of diagnosis in a ‘‘1-stop’’ approach.
To minimize potential complications, pa-
tients’ eligibility for office hysteroscopy
should be carefully assessed.
For better diagnostic accuracy, ideally,
hysteroscopy should be scheduled in the
follicular phase after the cessation of men-
struation. Irregular proliferative or luteal
phase endometrium may have irregular
topography and can be falsely interpreted
as endometrial polyps. Overinflation of the
uterine cavity with distension media can
cause cavity distortion and partially pro-
truding fibroids to disappear. Both CO2
and saline solution appear to provide equiv-
alent clinical outcomes and patient toler-
ance, although the superiority of the image
clarity is still debatable and is operator
dependent. In patients with AUB, there is
an unresolved controversy about the value
of hysteroscopy for the diagnosis of serious
endometrial disease, such as endometrial
hyperplasia and cancer. Although visual
inspection of the uterine cavity is fairly
sensitive for protruding lesions, adhesions
or asymmetric cavity, the accuracy of his-
tologic prediction of endometrial diseases
based on direct visualization varies. It is
generally high for endometrial cancer, with
641
an overall sensitivity of 86.4% and specific-
ity of 99.6% according to a quantitative
meta-analysis based on 56 studies,10 but
inaccurate for endometrial hyperplasia,
an overall sensitivity, specificity, negative
predicdictive value, and positive predic-
dictive value of 63.7%, 91.7%, 91.3%,
and 64.7%.11 Adding direct biopsy of
suspicious areas appeared to improve
the accuracy of endometrial hyperplasia
detection by hysteroscopy.9,12
TRANSVAGINAL
ULTRASONOGRAPHY AND SALINE-
INFUSION SONOHYSTEROGRAPHY
TVS is an inexpensive, noninvasive, con-
venient way to indirectly visualize the
endometrial cavity. Therefore, it is recom-
mended as a first-line diagnostic instru-
ment for assessing uterine pathology in
reproductive age women presenting with
AUB. The argument for using imaging
study is based on the fact that organic
pathology that may not be obvious on
physical examination may be the under-
lying cause of uterine bleeding. Ultraso-
nographic assessment is often an
extension of the physical examination
and can provide additional information
affecting management decision. Focal in-
tracavitary lesions are common in preme-
nopausal women with AUB refractory to
medical treatment and this number can be
as high as 56%.13
Postmenopausal women have also been
evaluated with TVS to exclude endometrial
cancer when bleeding was present. Accord-
ing to a 2009 American College of Obste-
tricians and Gynecologists Committee
Opinion14 a thin distinct endometrial echo
on TVSr4 mm has a risk of malignancy of
1 in 917, and therefore endometrial biopsy
is not required. In fact, if one does a biopsy
on such patients with a thin distinct endo-
metrial echo on TVS, it is common to not
successfully obtain tissue, or when tissue is
present, it is often so scant that it is insuffi-
cient for evaluation. However, previous
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642 Tsai and Goldstein
surgery, coexisting leiomyomas, axial ori-
entation, marked obesity, and adenomyosis
can limit the clear visualization of an endo-
metrial echo. In those situations, SIS find-
ings may be helpful to triage patient to:
(1) no anatomic pathology (no biopsy nec-
essary); (2) globally thick endometrium
(blind biopsy appropriate); and (3) focal
abnormalities (like polyps or focal thicken-
ing best approached with direct visualiza-
tion of hysteroscopy). The management of
incidental ultrasound finding of a thicken
endometrium in an asymptomatic postme-
nopausal woman remains controversial, the
consensus favors expectant management
because of low incidence of endometrial
malignancy in those cases, mostly inactive
polyps, although individualization might be
considered if patients are at high risk (dia-
betes, hypertension, obesity, etc.).15
When compared with TVS, SIS has
been shown to be superior in detecting
endometrial pathologies such as endome-
trial polyps and fibroids both in preme-
nopausal and postmenopausal women
with AUB. The accuracy of TVS is im-
paired when a small intracavitary lesion is
found. When SIS is not available, the use
of color flow or power Doppler imaging
to identify a feeder vessel is helpful for the
diagnosis of an endometrial polyp, with a
positive predictive value of 81.3%.16 The
diagnostic accuracy of intrauterine le-
sions can also be influenced by the timing
of the ultrasound in cycling premeno-
pausal women. This was supported in a
prospective blinded study by Wolman
et al17 in which there was a false-positive
rate of 27% in SIS performed from day 16
to 28, while there were none when the
procedure was performed before day 10.
In patients with irregular bleeding, an
empiric course of a progesterone such as
medroxyprogesterone acetate 10 mg daily
for 10 to 14 days as a ‘‘medical curettage’’
and then time the ultrasound evaluation
to the withdrawal bleed may be appropri-
ate.18 SIS and office hysteroscopy are
equally accurate in the diagnosis of
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endometrial pathology although hystero-
scopy is the most accurate test for poly-
poid lesions in the postmenopausal
group. SIS induces significantly less dis-
comfort than office hysteroscopy and
should therefore be considered the meth-
od of choice. In office practice, whether
SIS or hysteroscopy should be the next
step of management after an ultrasonog-
raphy suspicious for an intracavitary le-
sion will basically depend on the
availability of resources, health care pro-
viders’ preference but especially, clinical
indication. SIS is extremely useful to char-
acterize the depth of myometrial involve-
ment of leiomyomata, important for
assessing the feasibility and planning of
transcervical resection of submucosal fib-
roids. In case SIS is unavailable or there is
technical difficulty due to multiple fib-
roids, magnetic resonance imaging
(MRI) is an expensive but superior option
to provide accurate information on size,
location, and type of fibroid. In contrast,
hysteroscopy offers the advantage of di-
rect inspection of the uterine cavity, cer-
vical canal, and vagina, allowing the
differentiation of fibroid versus polyps
and direct sampling when a suspicious
lesion is encountered.
Office Management of AUB
After pregnancy and malignancy have
been excluded, treatment goals for AUB
patients include regulation of menstrual
cycles, minimization of blood loss, and
improvement in quality of life. For heavy
menstrual periods, the treatment aims to
prevent further worsening of anemia and
reduce the need for blood transfusion.
Quantitative estimation of actual blood
loss using the alkaline hematin method is
impractical in routine clinical practice.
Thus, therapeutic outcome measurement
relies on a patient’s subjective perception,
which correlates fairly with objective
quantification. A patient’s menstrual cal-
endar is helpful for the monitoring of a
 Office Management of Menstrual Disorder
therapeutic response and allows compar-
ison throughout the course of treatment.
A simple management guideline that is
helpful when dealing with AUB is as
follows. (1) Start always with medical
treatment before considering surgery un-
less you have a strong reason to do so. (2)
Not all uterine bleeding needs treatment,
expectant management can be carried out
after serious pathologies have been ruled
out. (3) Any therapeutic options should
take into consideration a patient’s desire
for future fertility and cultural back-
ground. (4) Empiric treatment should be
initiated, based on index of suspicion, if
pending test result or a definite diagnosis
cannot yet be established. (5) Uterine bleed-
ing may be the tip of iceberg of an under-
lying disease, so treat the patient and not
only the bleeding. (6) Many therapeutic
modalities lead to a similar outcome, so be
sure to discuss the risk, benefits, and alter-
natives of the available options.
Hysterectomy is the definitive treat-
ment for any AUB, but should not be
used as a first-line treatment for heavy
menstrual periods. Office management of
AUB and alternatives to hysterectomy
should be always considered as they may
provide temporary relief of bleeding
symptoms and delay or eliminate the need
for definitive surgical treatment. Older
women are more likely to benefit from
uterine preserving treatment because of
the bridge to menopause and such women
experience greater symptom resolution,
compared with women who were younger
(first treatment at age 40 y or under).
PHARMACOLOGICAL TREATMENT
HT
According to a recent survey conducted
among American Congress of Obstetri-
cians and Gynecologists members, the
most commonly selected first-line choice
for AUB treatment in the United States
was combined oral contraceptives. The
643
levonorgestrel intrauterine device (LNG-
IUD) was the next most frequently
selected option.19 Combined oral contra-
ceptive pill (COCP) can correct menstrual
irregularities resulting from oligoovula-
tion or anovulation and make menstrua-
tion more predictable. They can also
reduce excessive menstrual bleeding in
most affected women and is considered a
reasonable option for initial management
of menorrhagia. COCP is less effective for
the treatment of heavy menstrual periods
in women with organic pathology although
the response can be variable. Menstrual
blood loss is reduced about 50% in women
using COCP, and the reduction is most
apparent during the first 2 days of the
menstrual flow. Extended cycle or contin-
uous COCP with 20 mg ethinyl estradiol/
100 mg levonorgestrel formulation, either
84/7 regimens that shorten the hormone-
free interval and decrease the number of
days of bleeding per year, or the 365 regi-
men designed to eliminate bleeding alto-
gether, is associated with significant
reduced bleeding when compared with cy-
clic use. Shortening of the hormone-free
interval from 7 to 4 days significantly de-
creases the number of withdrawal bleeding
days in each cycle and increases the ame-
norrhea rate. For those women with a
contraindication to estrogen therapy, pro-
gesterone therapy or LNG-IUD can be an
alternative. Because of the levonorgestrel
effect on the endometrium, the duration
and amount of menstrual bleeding is re-
duced. This effect may begin during the
first menstrual cycle after the placement of
device, and bleeding becomes progressively
less over time. Many of the progesterone-
only long acting reversible contraceptive
methods have been used for the treatment
of menorrhagia. Patients should be coun-
seled about the inconvenience of break-
through bleeding observed during the
initial months of treatment. The timing of
complete suppression of the menstrual
cycle is variable depending on the method.
Amenorrhea is approximately 30% to 40%
www.clinicalobgyn.com
644 Tsai and Goldstein
and 20% to 80% in 12 months for single
rod progestin contraceptive implant and
LNG-IUD, respectively.20 Use of depot
medroxyprogesterone acetate (DMPA) re-
sults in relatively high rates of amenorrhea
by the fourth dose (approximately as
high as 90% in some studies) and has tradi-
tionally been used extensively to suppress
menses. In a single randomized controlled
study to compare the efficacy of LNG-IUD
to low-dose COCP for the management of
idiopathic menorrhagia, LNG-IUD was
found to be more effective with statistically
significantly less treatment failure (defined
as requiring medical or surgical treatment)
when compared with COCP, 11% versus
36%, respectively.21 According to a Co-
chrane review, cyclic progestogens adminis-
tered from day 15 or 19 to day 26 of the cycle
offer no advantage over other medical
therapies such as danazol, tranexamic acid
(TA), nonsteroidal anti-inflammatory drugs
(NSAIDs), and the LNG-IUD. Instead,
21-day oral progestogen therapy taken from
cycle day 5 to day 26 should be recom-
mended because it results in a significant
reduction in menstrual blood loss.22
Nonsteroidal Anti-Inflammatory Drugs
NSAIDs reduce prostaglandin synthesis by
inhibiting cyclooxygenase, thus reducing en-
dometrial prostaglandin levels that promote
angiogenesis and may have a role in aberrant
neovascularization leading to DUB. Oral
NSAIDs are an excellent treatment to re-
duce heavy menstrual bleeding. When com-
pared with placebo, they decrease menstrual
cramping and reduce menstrual blood loss
by 33%.23 They are less effective than TA,
danazol, or LNG-IUD but comparable with
oral luteal progestogen, COCP, and etham-
sylate. There is no evidence of a difference
between the individual NSAIDs (nap-
roxen and mefenamic acid) in reducing
heavy menstrual bleeding. Mefenamic acid
500 mg 3 times a day for 5 days and ibupro-
fen 600 mg every 6 hours or 800 mg every
8 hours are commonly prescribed during the
www.clinicalobgyn.com
first 3 days of menstrual cycle to reduce
blood loss and menstrual cramping.
TA
The Food and Drug Administration
(FDA) has recently approved an oral for-
mula of TA for clinical use in the United
States. Its pharmacological mechanism
involves reversibly blocking lysine-bind-
ing sites on plasminogen, preventing plas-
min and fibrin polymer interaction
resulting in fibrin degradation, stabilizing
clots, and reducing bleeding. TA is con-
traindicated in women with increased risk
for thromboembolism. TA has been rou-
tinely used for many years to reduce blood
loss and the need for blood transfusion
during and after surgical procedures. TA
has been used for the treatment of heavy
menstrual bleeding outside the United
States for several decades. TA’s therapeu-
tic effect is superior to placebo, NSAIDs,
ethamsylate, and luteal phase norethister-
one and results in significant reduction in
objective measurement of idiopathic
heavy menstrual bleeding.24 Interestingly,
TA treatment has no effect on the dura-
tion of bleeding when compared with a
control group. TA is also effective as a
treatment for significantly relieving un-
scheduled bleeding and menorrhagia in-
duced by DMPA and intrauterine device,
respectively. In all studies analyzed, only
mild to moderate side effects were re-
ported, mostly gastrointestinal, and there
were no reports of thromboembolic
events with the use of TA.24 Nonetheless,
the effectiveness of TA treatment on heavy
menstrual bleeding secondary to uterine
fibroid remains unknown and further study
is needed. The FDA has approved TA at a
oral dosage of 1300 mg (two 650-mg tab-
lets) 3 times daily for 5 days in each men-
strual cycle.25 The oral bioavailability of
TA is only about 35%, which makes fre-
quent administrations necessary. The dis-
advantages of frequent administrations
include decreased patient compliance and
increased risk of gastrointestinal side
 Office Management of Menstrual Disorder
effects most commonly nausea, vomiting,
and diarrhea. The perspective of using a
single antifibrinolytic medication to relieve
a common and multietiologic gynecologic
condition is exciting, and it is potentially
cost saving by decreasing the utilization of
invasive diagnosis and surgery for treating
heavy menstrual bleeding.
ENDOMETRIAL ABLATION
Endometrial ablation is a minimally in-
vasive alternative for the treatment of
heavy menstrual bleeding and is associ-
ated with high level of patient satisfaction.
It is usually reserved for patients refrac-
tory to medical treatment and who wish to
avoid a definite treatment with hysterec-
tomy. Although endometrial ablation is a
less invasive surgical alternative to
hysterectomy, it does not eliminate surgi-
cal risk and is followed by further surgery
within 4 years in up to 38% of the women
who undergo this treatment.26,27 Endo-
metrial ablation should be considered as
an alternative to hysterectomy especially
in older women who opted to retain their
uterus and not in women with desire of
future fertility. Patient age is an important
predictor of treatment success. Younger
women who undergo endometrial abla-
tion experience higher rates of hysterec-
tomy than older women (40% for women
40 y old vs. 20% for women 45 to 50 y
old), irrespective of the method used.28 In
contrast to the resectoscopic endometrial
ablation, several new ablation devices
offer the advantage of being performed
in an office setting. There are currently 5
FDA-approved nonresectoscopic abla-
tion devices: microwave endometrial
ablation system (MEAS), Novasure,
ThermaChoice, Her Option (cryother-
apy), and Hydrothermo ablator. Patient
satisfaction and amenorrhea rate associ-
ated with endometrial ablation ranges
from 86% to 96% and 13.2% to 55.3%
respectively, depending on the devices
used. The desired treatment outcome is
645
the improvement of a patient’s quality
of life with reduction of blood loss but
not necessarily amenorrhea. The relative
contraindication of using endometrial
ablation device is the size of uterine cavity
and presence of submucosal fibroids.
Most of the manufacturers recommend
maximum uterine length by sounding of
10 cm except MEAS which is 14 cm. Nova-
sure, MEAS, and TermoChoice devices are
licensed for ablation of the uterine cavity
with submuosal fibroids of <3 cm. Abso-
lute contraindications include pregnancy,
uterine perforation, and endometrial malig-
nancy. Although the infection rate is low
with ablation procedures, postablation tu-
bal sterilization syndrome can occur in
patients with prior tubal ligation because
of residual endometrial proliferation form-
ing hematometrea in the cornual area.
Treatment requires hysteroscopic decom-
pression. Serious complications associated
with uterine perforation, thermal injury to
the bowel, and even death have been re-
ported with all 5 FDA-approved endome-
trial ablation devices.29 Thermal injuries to
the vagina and vulva have been described
with Hydrothermo ablator devices that in-
fuse heated fluid into the uterine cavity to
destroy endometrium.
It is currently unknown what constitutes
an appropriate preablation endometrial as-
sessment and postablation surveillance; the
scarred uterine cavity, as a result of endo-
metrial destruction, makes the diagnosis of
malignancy even more difficult, although
diagnosis of cancer through endometrial
sampling has been reported. Careful patient
selection seems to be the key to decrease the
occurrence of endometrial cancer after
ablation. In a recent systematic review
where 22 postablation endometrial cancer
cases were reviewed,30 the time to diagnosis
of endometrial cancer ranges from 2 weeks
to 10 years after endometrial ablation. Most
of the patients had symptoms of persistent
bleeding or pain after the procedure.
Eighty-six percent of the cancer patients
presented with risk factors for endometrial
www.clinicalobgyn.com
646 Tsai and Goldstein
cancer such as obesity, complex atypical
endometrial hyperplasia, diabetes, hyperten-
sion, and postmenopausal status. Thus, en-
dometrial ablation should be restricted to
premenopausal women who have low-risk
factors for endometrial cancer and who have
documented normal endometrial histopa-
thologic features at preablation evaluation.
In a systematic review and meta-anal-
ysis to compare the effect of levonrgestrel
intrauterine system and endometrial abla-
tion in reducing heavy menstrual bleed-
ing, 6 randomized controlled trials that
included 390 women (196 levonorgestrel
intrauterine system, N = 196; endome-
trial ablation, N = 194) were retrieved (3
were first-generation and 3 were second-
generation endometrial ablation devices).
The efficacy of LNG-IUD in the manage-
ment of heavy menstrual bleeding appears
to have similar therapeutic effects to that
of endometrial ablation up to 2 years after
treatment.31 According to the same study,
the rate of hysterectomy or (new or re-
peat) ablation was similar between 2 treat-
ment modalities in the studies included in
the meta-analysis: 11% and 10% for the
LNG-IUD and endometrial ablation, re-
spectively. LNG-IUD, an effective contra-
ceptive method, offered an additional
advantage of being a less expensive and
reversible method as compared with perma-
nent endometrial destruction with ablation
devices. Both LNG-IUD and nonresecto-
scopic endometrial ablation are not suitable
for treating menorrhagia with an enlarged
uterine cavity. LNG-IUS has higher rate of
expulsion and endometrial ablation proce-
dures are more likely to fail.
According to recent reviews, the different
techniques of second-generation endome-
trial ablation appear to be similar in terms
of efficacy. Two of the most commonly used
second-generation office endometrial abla-
tion devices in the United States: Bipolar
radiofrequency ablation device-Novasure
and thermal balloon ablation-Therma-
choice, have comparable 6-month postabla-
tion amenorrhea rates and same efficacy in
www.clinicalobgyn.com
the treatment of heavy menstrual period.32
Because of the shorter treatment cycle, No-
vasure appears to be better tolerated by
patients when performed in an office setting
as compared to Thermachoice where 5% of
the patient could not complete the ablation
due to procedure-related discomfort.
ANOVULATORY BLEEDING
Anovulatory uterine bleeding is a com-
mon occurrence in reproductive age
patients, especially adolescents and peri-
menopausal women. Most of anovulatory
uterine bleeding will respond to medical
treatment. The pattern of anovulatory
bleeding varies and ranges from spotting
and oligomenorrhea to heavy and pro-
longed uterine bleeding. In reproductive
aged women, after excluding pregnancy
and endometrial malignancy, acute treat-
ment to stop bleeding will usually consist
of progesterone therapy to induce com-
plete shedding of the dysfunctional endo-
metrium. Medroxyprogesterone acetate
10 mg is given for 10 to 14 days, and
bleeding usually stops a few days after
the initiation of the medication and a self-
limited withdrawal bleed will take place 2
to 7 days after progesterone is discontin-
ued. After that, monthly cyclic progester-
one or COCP can be used to regulate the
cycle. In adolescent girls with acute and
profuse bleeding, high doses of conju-
gated equine estrogen can be used orally
at 2.5 mg every 6 hours, or intravenously,
25 mg every 4 hours up to 24 hours fol-
lowed by tapering down with COCP. If
estrogen therapy is contraindicated, high
doses of oral medroxyprogesterone acetate
has been shown to be an effective alterna-
tive in managing acute excessive anovula-
tory bleeding when administered at a total
dose of 60 to 120 mg during the first day
and 20 mg/d for the following 10 days.33
For chronic anovulatory bleeding in ado-
lescents, cyclic COCP and progestogens are
equally effective. In treating abnormal
bleeding in patients with PCOS, health care
 Office Management of Menstrual Disorder
providers should be alert to the possibility of
more serious underlying associated comor-
bidities: PCOS is considered to be a risk
factor for the development of metabolic
syndrome due to insulin resistance with or
without obesity. Life style modification
along with diet and exercise are important
in obese patients as weight loss is associated
with return to spontaneous menstrual
cycles. The use of insulin-sensitizing drugs
such as metformin to decrease insulin resist-
ance can help to achieve ovulation and
regulate menstrual periods. Treatment with
cyclic progesterone or COCP is recom-
mended to prevent endometrial hyperplasia
and cancer, which can be long-term sequelae
of unopposed estrogen.
ENDOMETRIAL POLYPS
The prevalence of symptomatic polyps has
been reported to range from 13% to 50%
and is commonly associated with metror-
rhagia, menorrhagia, and metromenorrha-
gia. The causative association between
endometrial polyps and abnormal bleeding
remains elusive because up to 34% of
polyps are found in asymptomatic women.
Although the natural history of endometrial
polyps is unknown, small polyps have been
described to undergo spontaneous regres-
sion in 1 study. COCP use is a known
protective factor for the development of
endometrial polyps and could be used to
treat symptomatic polyps. Expectant man-
agement or treatment with COCP can be a
reasonable alternative to transcervical poly-
pectomy in low-risk premenopausal patient.
The wide spread utilization of ultraso-
nography for routine pelvis organ screening
by gynecologists has greatly increased the
incidental diagnosis of endometrial polyps.
The most common question is whether all
endometrial polyps should be removed be-
cause of malignancy concern? and if not,
which patients warrant polypectomy? The
malignant potential of endometrial polyps
is relatively low ranging from 0.5% to 4.8%
depending on the population studied; the
647
risk is significantly increased with meno-
pause and bleeding.34,35 Current consensus
is any endometrial polyp in postmeno-
pausal women presenting with abnormal
bleeding should be removed, for asympto-
matic women, expectant management is
recommended. In premenopausal women,
because of the low incidence of malignant
polyps, polypectomy is only indicated for
bleeding symptom relief.
UTERINE LEIOMYOMA
The most common symptoms in women
with leiomyoma seeking medical treatment
are pelvic pressure and AUB. The bleeding
symptoms can vary from heavy menstrual
flow to prolonged and persistent bleeding.
Hysterectomy remains the most common
surgical treatment for leiomyoma because it
is the only definitive treatment and elimi-
nates the possibility of recurrence. Medical
therapy and minimal invasive procedures
tend to provide short-term symptom relief
and although many patients require defin-
itive surgical management within a few
years, those alternatives to hysterectomy
can delay or eliminate the need for uterine
extirpation. Increased size, but not the
number or location of fibroids, is associated
with worsening of uterine bleeding, and
nonsubmucosal leiomyomatas are associ-
ated with heavy bleeding to the same extent
as submucosal leiomyomatas. Premeno-
pausal women may experience rapid enlarg-
ing fibroid because of a transient increased
in estrogen levels. It is usually not related to
uterine malignancy and should not be used
as basis for hysterectomy.
For women whose only symptom is
heavy bleeding or prolonged menses,
there are several options including ste-
roidal therapies such as COCP and
the LNG-IUD. Contraceptive patches,
DMPA, and vaginal rings likely work in
a similar manner. Hysteroscopic resection
of type 0 and I submucosal leiomyomas
have been shown to decrease heavy men-
strual bleeding,36 even after an incomplete
www.clinicalobgyn.com
648 Tsai and Goldstein
resection. The significant factors for the
risk of failure of treatment include young-
er age, increasing number of and larger-
sized myomas, intramural extension, and
incomplete resection. Fifty percent of pa-
tients with incomplete resection required
no further treatment.
UTERINE ARTERY EMBOLIZATION
(UAE)
UAE is a procedure performed to deliver
small particles to obstruct the arterial supply
of part or all of the uterus causing ischemic
degeneration of uterine fibroids. Within 2 to
4 months after embolization, a 40% to 60%
reduction of uterine volume may be ex-
pected, however, symptomatic improve-
ment may be achieved without remarkable
change in myoma size. In reviews of pub-
lished data, the clinical success rate meas-
ured by improvement in fibroid-related
symptoms, eg, menstrual loss, was at least
85%.37 UAE is associated with a higher rate
of minor postprocedural complications such
as vaginal discharge, postpuncture hemato-
ma, and postembolization syndrome (pain,
fever, nausea, vomiting), as well as more
unscheduled visits and higher readmission
rates after discharge, compared with
hysterectomy.38 UAE has short-term ad-
vantages over surgery. Mid-term and long-
term benefits were similar, except for a high-
er reintervention rate after UAE. Although
successful pregnancy has been reported after
UAE, patients should be counseled about
the increased risk of uterine rupture and
abnormal placentation in future pregnan-
cies associated with the procedure. Cur-
rently, UAE is not recommended for
women who desire future fertility.
HIGH-INTENSITY FOCUS
ULTRASOUND (HiFus)
HiFus is a noninvasive treatment of leio-
myoma. The high-intensity ultrasound en-
ergy penetrates through the abdominal wall
to target specifically the fibroid. The heat
generated causes protein denaturation and
www.clinicalobgyn.com
coagulative necrosis of fibroid tissue. The
real-time monitoring of thermal spread to
nontargeted tissues is possible using MRI in
the only FDA-approved device (ExAblate
2000/Insightec Corp.). The safety concern
exists regarding inadvertent thermal spread
in case of pelvic adhesion where the bowel
might be situated next to the fibroid. Pa-
tients are usually excluded from HiFus
treatment when there is abdominal scarring,
high T2 signal intensity, pedunculated leio-
myomas, severe adenomyosis, menopause,
leiomyoma >10 cm, 5 or more leiomyomas
>3 cm, contraindications to MRI, weight
>250 lb, or inability of the patient to lie
prone for several hours. HiFus is available
only in few centers in the United States.
Several investigators are studying HiFus
that would potentially be provided by trans-
vaginal ultrasound and thus, performed by
gynecologists. Leiomyoma symptom relief
after HiFus at 1 year postprocedure is as
high as 88%.39 In a prospective 3-year
follow up study on 51 leiomyomata from
40 patients after Hifus treatment, the mean
baseline volume of treated leiomyomata was
336.9 mL. The mean volume decrease
in treated leiomyomata was 32.0% (P<
0.001), and, in the uterus, the volume de-
crease was 27.7% (P<0.001) at 3 years.
Thirty-one percent of women who complete
HiFus elected alternative treatments within
3 years secondary to treatment failure.
There were no long-term complications.
Further studies are needed to validate the
long-term effectiveness and the extended
application of HiFus.
Conclusions
Diagnosis and management of AUB still
poses challenges to most gynecologists in
their office practice. Available evidences
suggest that a significant portion of pa-
tients with AUB can be diagnosed and
managed in the office with currently avail-
able uterine-sparing treatment. These ap-
proaches are likely to result in short-term
improvement of the quality of life of
 Office Management of Menstrual Disorder
women suffering from the bleeding com-
plaints and, many times, delaying a
hysterectomy, which is considered the
definitive treatment for AUB.
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