Abnormal Uterine Bleeding

in Premenopausal Women
Noah Wouk, MD, Piedmont Health Services, Prospect Hill, North Carolina
Margaret Helton, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Abnormal uterine bleeding is a common symptom in women. The acronym PALM-COEIN facilitates classification, with PALM
referring to structural etiologies (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia), and COEIN referring to non-
structural etiologies (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified). Evaluation
involves a detailed history and pelvic examination, as well as laboratory testing that includes a pregnancy test and complete
blood count. Endometrial sampling should be performed in patients 45 years and older, and in younger patients with a sig-
nificant history of unopposed estrogen exposure. Transvaginal ultrasonography is the preferred imaging modality and is
indicated if a structural etiology is suspected or if symptoms persist despite appropriate initial treatment. Medical and surgical
treatment options are available. Emergency interventions for severe bleeding that causes hemodynamic instability include
uterine tamponade, intravenous estrogen, dilation and curettage, and uterine artery embolization. To avoid surgical risks
and preserve fertility, medical management is the preferred initial approach for hemodynamically stable patients. Patients
with severe bleeding can be treated initially with oral estrogen, high-dose estrogen-progestin oral contraceptives, oral pro-
gestins, or intravenous tranexamic acid. The most effective long-term medical treatment for heavy menstrual bleeding is the
levonorgestrel-releasing intrauterine system. Other long-term medical treatment options include estrogen-progestin oral
contraceptives, oral progestins, oral tranexamic acid, nonsteroidal anti-inflammatory drugs, and depot medroxyprogester-
one. Hysterectomy is the definitive treatment. A lower-risk surgical option is endometrial ablation, which performs as well
as the levonorgestrel-releasing intrauterine system. Select patients with chronic uterine bleeding can be treated with myo-
mectomy, polypectomy, or uterine artery embolization. (Am Fam Physician. 2019;99(7):​435-443. Copyright © 2019 American
Academy of Family Physicians.)

Abnormal uterine bleeding is a common condition, Definitions

with a prevalence of 10% to 30% among women of reproduc- Abnormal uterine bleeding is a symptom, not a diagnosis;​
tive age.1 It negatively affects quality of life and is associated the term is used to describe bleeding that falls outside pop-
with financial loss, decreased productivity, poor health, and ulation-based 5th to 95th percentiles for menstrual regular-
increased use of health care resources.2-4 In 2011 the Interna- ity, frequency, duration, and volume (Table 1).7 Abnormal
tional Federation of Gynecology and Obstetrics convened a bleeding is considered chronic when it has occurred for
working group that produced standardized definitions and most of the previous six months, or acute when an episode
classifications for menstrual disorders, which the American of heavy bleeding warrants immediate intervention.5 Inter-
College of Obstetricians and Gynecologists subsequently menstrual bleeding is bleeding that occurs between oth-
endorsed.5,6 The updated terminology pertains only to non- erwise normal menstrual periods.7 Use of imprecise terms
pregnant women of reproductive age, which is the scope of such as menorrhagia, metrorrhagia, and dysfunctional
this review. uterine bleeding is now discouraged.

Differential Diagnosis
Additional content available at https://​w ww.aafp.org/
Although the uterus is often the source, any part of the
afp/2019/0401/p435.html.
female reproductive tract can result in vaginal bleeding.
CME This clinical content conforms to AAFP criteria for con-
tinuing medical education (CME). See CME Quiz on page 418.
Women may also mistake bleeding from nongynecologic
sites (e.g., bladder, urethra, perineum, anus) as vaginal
Author disclosure:​​ No relevant financial affiliations.
bleeding. The prevalence of conditions that cause abnormal
Patient information:​ A handout on this topic is
available at https://​family​doctor.org/condition/
bleeding varies according to age. For example, anovulation is
abnormal-uterine-bleeding/. more common in adolescents and perimenopausal women,
whereas the prevalence of structural lesions and malignancy

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 ABNORMAL UTERINE BLEEDING

increases with age.8 The differential diagnosis of abnormal

WHAT IS NEW ON THIS TOPIC uterine bleeding is presented in Table 2.9-11
The most common causes of abnormal uterine bleeding
Abnormal Uterine Bleeding are described with the acronym PALM-COEIN.5 The eti-
The acronym PALM-COEIN facilitates the classification of ologies in the PALM group (polyp, adenomyosis, leiomy-
abnormal uterine bleeding, with PALM referring to structural oma, malignancy and hyperplasia) are structural and can
etiologies (polyp, adenomyosis, leiomyoma, malignancy and be imaged or biopsied. The etiologies in the COEIN group
hyperplasia), and COEIN referring to nonstructural etiologies
(coagulopathy, ovulatory dysfunction, endometrial, iatro-
(coagulopathy, ovulatory dysfunction, endometrial, iatro-
genic, not otherwise classified). genic, not otherwise classified) are nonstructural. These
etiologies are not mutually exclusive, and patients may have
Among medical therapies, the 20-mcg-per-day formulation more than one cause.
of the levonorgestrel-releasing intrauterine system (Mirena)
is most effective for decreasing heavy menstrual bleeding
(71% to 95% reduction in blood loss) and performs similarly to POLYP
The lifetime prevalence of endometrial polyps ranges
hysterectomy when quality-adjusted life years are considered.
from 8% to 35%, and their incidence increases with age.12
Intermenstrual bleeding is the most
common presenting symptom, but
TABLE 1 many polyps are asymptomatic. Phys-
ical examination findings are typically
Definitions of Normal and Abnormal Menstrual Bleeding unremarkable, except for cases in
Menstrual cycle terms Descriptive terms Definition which the polyps prolapse through the
cervix.13 Although they can develop
Frequency (interval Infrequent > 38 days
between the start of each into malignancy, approximately 95%
menstrual cycle) Normal 24 to 38 days of symptomatic polyps are benign, and
Frequent < 24 days the risk of malignancy is even lower in
premenopausal women.14
Regularity (variation of Regular ± 2 to 20 days over 12 months
menstrual cycle length,
Irregular > 20 days over 12 months ADENOMYOSIS
measured over 12 months)
The presence of endometrial tissue
Duration of menstruation Shortened < 4.5 days in the myometrium is known as ade-
Normal 4.5 to 8 days nomyosis. Its prevalence ranges from
5% to 70%, and its association with
Prolonged > 8 days
abnormal uterine bleeding is unclear.15
Volume (total blood loss Light < 5 mL Many patients are asymptomatic, but
each menstrual cycle)
Normal 5 to 80 mL
those who have symptoms typically
report painful, heavy, or prolonged
Heavy > 80 mL menstrual bleeding. Examination may
Other terms Amenorrhea No bleeding for 90 days reveal a dense, enlarged uterus.
Primary Absent menarche by 15 years LEIOMYOMA
amenorrhea of age
Leiomyomas (also called fibroids) are
Secondary Amenorrhea for 6 months with benign tumors arising from the uter-
amenorrhea previously regular menstrual cycles
ine myometrium. Their prevalence
Menopause Amenorrhea for 12 months with- increases with age;​they are eventually
out other apparent cause found in up to 80% of all women.16
Precocious Menarche before 9 years of age Most leiomyomas are asymptomatic,
menstruation but bleeding is a common presenting
symptom and typically involves heavy
Adapted with permission from Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO rec-
ommendations on terminologies and definitions for normal and abnormal uterine bleeding. or prolonged menses. Larger leiomy-
Semin Reprod Med. 2011;29(5):389. omas are more likely to be associated
with abnormal uterine bleeding.17

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 TABLE 2 TABLE 3

Differential Diagnosis of Abnormal Risk Factors for Endometrial Cancer

Uterine Bleeding Risk factor Relative risk
Coagulopathies
Major
Iatrogenic Long-term use of unopposed estrogen 10 to 20
Anticoagulants
Hereditary nonpolyposis colorectal 6 to 20
Antipsychotics cancer (Lynch syndrome)
Copper intrauterine device
Estrogen-producing tumor >5
Hormonal contraception or other hormone therapy
Tamoxifen Minor
Obesity 2 to 5
Infection
Acute or chronic endometritis Nulliparity 3
Pelvic inflammatory disease Polycystic ovary syndrome 3
Ovulatory dysfunction History of infertility 2 to 3
Hyperprolactinemia
Late menopause 2 to 3
Immature hypothalamic-pituitary-adrenal axis (adolescence)
Intense exercise or stress Tamoxifen use 2 to 3
Ovarian follicle decline (perimenopause)
Type 2 diabetes mellitus, hypertension, 1.3 to 3
Polycystic ovary syndrome gallbladder disease, or thyroid disease
Starvation (including eating disorders)
Information from references 18 and 20.
Thyroid disorders

Pregnancy
Abortion COAGULOPATHY
Abruption or subchorionic hemorrhage Approximately 20% of patients with heavy menstrual
Ectopic pregnancy bleeding have a bleeding disorder, and the prevalence in
adolescent girls who bleed heavily is even higher.21-23 Von
Structural
Willebrand disease and platelet dysfunction are the most
Adenomyosis
common coagulopathies associated with abnormal uterine
Endometriosis
bleeding.24 In addition to heavy menstrual bleeding, ado-
Leiomyoma lescents with bleeding disorders may report irregular men-
Malignancy or hyperplasia strual bleeding.25
Polyp

Information from references 9 through 11. OVULATORY DYSFUNCTION

A variety of endocrine disorders can lead to ovulatory dys-
function (Table 2).9-11 Infrequent or absent ovulation during
Patients may report pelvic pain or pressure, and on exam- the first few years after menarche and during perimeno-
ination the uterus may be enlarged or irregularly contoured. pause is common and not necessarily a sign of underlying
More information on the diagnosis and treatment of leiomy- pathology.26 Menstrual bleeding caused by ovulatory dys-
omas is available in a previous American Family Physician function is often irregular, heavy, or prolonged.
article (https://​w ww.aafp.org/afp/2017/0115/p100.html).
ENDOMETRIAL
MALIGNANCY AND HYPERPLASIA Primary disorders of endometrial hemostasis typically
Abnormal uterine bleeding is the most common symptom occur in the setting of predictable ovulatory cycles and are
of endometrial cancer.18 Although the prevalence of endo- likely due to vasoconstriction disorders, inflammation, or
metrial cancer increases with age, close to one-fourth of infection. Endometrial dysfunction is poorly understood;​
new diagnoses occur in patients younger than 55 years.19 there are no reliable diagnostic methods, and it should be
Long-term unopposed estrogen exposure is the primary considered only after other causes are excluded.5
risk factor (Table 3).18,20 Bleeding patterns in patients with
uterine malignancy are highly variable. More information IATROGENIC
on the diagnosis and management of endometrial cancer A variety of medical treatments can provoke abnormal
is available in a previous American Family Physician article uterine bleeding. Hormonal contraception is the most com-
(https://​w ww.aafp.org/afp/2016/0315/p468.html). mon cause of iatrogenic uterine bleeding (i.e., breakthrough

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 ABNORMAL UTERINE BLEEDING
FIGURE 1

Initial history or physical examination

suggests acute or severe blood loss?

No

  A Structured history and physical examination

Pregnancy test
Complete blood count
Cervical cancer screening (if due)

Additional evaluation if clinically indicated Address the underlying etiology, if apparent

Suspected Age ≥ 45 years Abnormal Infectious cause suspected:

Initial treatment options for severe
coagulopathy?* or elevated risk bimanual exam- test for gonorrhea, chla-
abnormal uterine bleeding in hemo-
of endometrial ination findings mydia, trichomoniasis
dynamically stable women:
carcinoma?† or symptoms that Hormonal cause suspected:
persist despite High-dose estrogen-progestin oral
Review platelet count; evaluate for anovulation,
treatment? contraceptives
check prothrom- thyroid disorder, hyperpro-
bin time and partial Endometrial lactinemia, polycystic High-dose oral progestins
thromboplastin time biopsy ovary syndrome Intravenous tranexamic acid
Transvaginal Endometrial ablation
ultrasonography Long-term medical therapy options:
Abnormal, or coag- Abnormal Positive or abnormal Levonorgestrel-releasing intrauterine
ulopathy strongly system (Mirena)
suspected‡ Abnormal
Estrogen-progestin oral contraceptives
Oral progestins
Oral tranexamic acid (Lysteda)
Nonsteroidal anti-inflammatory drugs
Further evaluation and treatment as indicated
Depot medroxyprogesterone
(Depo-Provera)
Long-term surgical options:
Endometrial ablation
Uterine artery embolization
Hysterectomy

Evaluation and management of abnormal uterine bleeding.

*—The likelihood of a bleeding disorder increases if any of the following historical clues are present: heavy menstrual bleeding since menarche;
history of postpartum hemorrhage, surgical bleeding, or bleeding with dental procedures; or two or more of the following: frequent gum bleeding,
bruising > 5 cm at least monthly, epistaxis at least monthly, or family history of abnormal bleeding. 25

Information from references 6, 18, and 26 through 30.

bleeding).5 Other causative agents include noncontracep- conditions that do not otherwise fit into the classification
tive hormone therapy, drugs that interfere with sex steroid system, such as cesarean scar defects, which can cause post-
hormone function or synthesis (e.g., tamoxifen), anticoagu- menstrual spotting when blood collects in the niche caused
lants, and dopamine antagonists (e.g., tricyclic antidepres- by the scar.
sants, some antipsychotics).
Diagnostic Evaluation
NOT OTHERWISE CLASSIFIED The approach to patients presenting with abnormal uterine
This category contains poorly understood conditions, bleeding includes assessing for hemodynamic instability
rare disorders (e.g., arteriovenous malformations), and and anemia, identifying the source of bleeding, pregnancy

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 total blood loss, but quantitative assessment is impractical
Yes in routine clinical practice. Historical clues such as pass-
ing blood clots or changing pads/tampons at least hourly
Assess hemodynamic stability
suggest heavy menstrual bleeding.31 A history of postcoital
bleeding may indicate cervicitis, ectropion, or, rarely, cervi-
cal cancer, whereas abdominopelvic pain may suggest infec-
Stable Unstable
tion, structural lesions, or endometriosis.
Clinicians may underestimate the prevalence of coagu-
lopathies among patients with abnormal uterine bleeding.32
Continue evaluation Standard resuscitative measures These conditions should be considered in women with a
family history of abnormal bleeding or a personal history
Go to   A Emergency treatment options: of heavy menstrual bleeding since menarche, or symptoms
Intrauterine tamponade such as frequent bruising, bleeding gums, epistaxis, post-
(temporizing measure) partum hemorrhage, or bleeding with surgical and dental
Intravenous conjugated estrogen procedures.27
Dilation and curettage
If severe bleeding persists:
PHYSICAL EXAMINATION
Uterine artery embolization
An examination of the pelvis, including speculum and
Hysterectomy
bimanual examinations, is an important aspect of the evalu-
ation of abnormal uterine bleeding. Care should be taken to
Patient stabilized examine all potential bleeding sites, including the urethra,
perineum, and anus. Cervical cancer screening should be
If necessary, continue evaluation
performed if it is not up to date. Pelvic examination can be
deferred in adolescents if the patient is not sexually active,
neither trauma nor infection is suspected, and the response
Go to   A to initial treatment is adequate.33

LABORATORY TESTING
All patients with abnormal uterine bleeding should be
evaluated for pregnancy with a urine or serum human
chorionic gonadotropin test, and for anemia and thrombo-
cytopenia with a complete blood count.6 Thyroid function
should be evaluated in patients with signs or symptoms of
thyroid disease, or if the initial workup does not reveal a
likely cause.6,28,34 Additional hormonal tests (e.g., prolactin,
androgens, estrogen) are indicated only if history or exam-
†—Risk factors include a history of exposure to unopposed estrogen
ination findings suggest a specific hormonal cause.26,28 The
(Table 3), failed medical management, and persistent bleeding.
‡—Initial screening tests may be normal in the setting of some coagu- platelet count, prothrombin time, and partial thromboplas-
lopathies, with diagnosis requiring further testing and possibly hema- tin time can be initial screening tests when a bleeding disor-
tology consultation.
der is suspected, but results may be normal in women with
von Willebrand disease or other bleeding disorders. Diag-
nosing a bleeding disorder typically requires additional
testing, and determining whether evaluation for endome- testing, often in consultation with a hematologist.27
trial carcinoma is indicated (Figure 1).6,18,26-30 The broad Because older age is an important risk factor for endo-
differential diagnosis necessitates a detailed history and metrial cancer, all patients with abnormal uterine bleeding
physical examination. who are 45 years or older should undergo endometrial sam-
pling.18 Younger women should undergo sampling if they
BLEEDING HISTORY have a history of unopposed estrogen exposure, if medical
A description of the bleeding pattern should be elicited, management fails, or if bleeding symptoms persist.6 Office-
including frequency, duration, regularity, and volume. based endometrial biopsy is the preferred approach, with
Heavy menstrual bleeding is defined as more than 80 mL of hysteroscopic dilation and curettage reserved for instances

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 ABNORMAL UTERINE BLEEDING
TABLE 4

Treatment Options for Medical Management of Abnormal Uterine Bleeding

Drug Suggested dosage Notes

Acute bleeding
Conjugated equine estrogen Hemodynamically unstable:​ Follow treatment with a progestin to provoke withdrawal
25 mg intravenously every 4 to bleeding;​do not use in patients at increased risk of thrombosis
6 hours for up to 24 hours
Hemodynamically stable:​2.5 mg
orally every 6 hours for 21 days

Estrogen-progestin oral 1 monophasic pill containing Other regimens also effective;​do not use in patients at
contraceptives 35 mcg of ethinyl estradiol orally increased risk of thrombosis
3 times daily for 7 days

Progestins Norethindrone, 5 mg orally Other high-dose oral progestins are also effective
3 times daily for 7 days

Tranexamic acid 10 mg per kg intravenously every Faster onset if given intravenously;​do not use in patients at
8 hours or 20 to 25 mg per kg increased risk of thrombosis
orally every 8 hours

Chronic bleeding
Depot medroxyprogesterone 150 mg intramuscularly or Unscheduled bleeding is a common initial adverse effect,
(Depo-Provera) 104 mg subcutaneously every but one-half of patients become amenorrheic after 12 months
13 weeks of use

Estrogen-progestin oral 1 monophasic pill containing Other routes (transdermal patch, intravaginal ring) are likely
contraceptives 35 mcg of ethinyl estradiol daily also effective;​regimens with no or fewer hormone-free inter-
vals may be more effective

Levonorgestrel 52-mg (20-mcg-per-day) intra- Effectiveness data are based primarily on trials involving the
uterine device (Mirena) 20-mcg-per-day device;​effect on bleeding suppression may
wane before contraceptive effectiveness expires

Nonsteroidal anti-inflammatory Naproxen, 500 mg orally 2 times Other oral nonsteroidal anti-inflammatory drugs are also
drugs daily effective;​administer only while patient is bleeding;​do not use
in patients with coagulopathy

Progestins Norethindrone, 2.5 to 5 mg Other oral progestins are also effective;​administration during
orally once daily only the luteal phase is significantly less effective for treating
heavy bleeding

Tranexamic acid (Lysteda) 1,000 to 1,500 mg orally 3 times Faster onset if given intravenously;​do not use in patients at
daily increased risk of thrombosis

Note:​The 2016 U.S. medical eligibility criteria for contraceptive use, published by the Centers for Disease Control and Prevention (https://​w ww.
cdc.gov/mmwr/volumes/65/rr/rr6503a1.htm), can be referenced to guide the use of the hormonal treatments listed in this table.
Information from references 37 through 42.

in which office sampling fails, is inadequate, or cannot be lesions.36 Routine use of magnetic resonance imaging is
performed.35 Blind sampling may miss focal lesions, so hys- discouraged but can be considered if sonographic imaging
teroscopic dilation and curettage should be performed if is inadequate.6
symptoms persist despite normal biopsy results.18
Management
IMAGING Multiple factors should be considered when choosing among
Indications for pelvic imaging include abnormalities pal- treatment options for abnormal uterine bleeding (Table 4),37-42
pated on bimanual examination or symptoms that persist including the cause and acuity of the bleeding, fertility and
despite initial treatment.6 Transvaginal ultrasonography is contraceptive preferences, medical comorbidities, adverse
the first-line approach for most patients, although saline effects, cost, and relative effectiveness. If the underlying
infusion sonohysterography (the infusion of sterile saline cause of bleeding can be identified and treated, symptoms
into the endometrial cavity while transvaginal ultraso- may resolve without the need for additional intervention.
nography is performed) is better at detecting intracavitary Anemia is an indication for treatment, as is bleeding that

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 ABNORMAL UTERINE BLEEDING

negatively affects the patient’s quality

of life. Because exposure to unopposed SORT:​KEY RECOMMENDATIONS FOR PRACTICE
estrogen increases the risk of endome-
trial cancer, treatment of anovulatory Evidence
Clinical recommendation rating References
abnormal uterine bleeding involves
inducing ovulatory cycles or admin- The International Federation of Gynecology and C 5, 6
istering supplemental progesterone Obstetrics classification system should be used to char-
acterize abnormal uterine bleeding.
to antagonize estrogen’s proliferative
effect on the endometrium. All patients with abnormal uterine bleeding should be C 6
tested for pregnancy and anemia.
EMERGENT TREATMENT
Endometrial biopsy should be performed in all patients C 6
Occasionally, abnormal uterine bleed- with abnormal uterine bleeding who are 45 years or
ing is of sufficient quantity or duration older, in younger patients with a significant history of
that emergent attention is required. unopposed estrogen exposure, persistent bleeding, or
in whom medical management is ineffective.
For hemodynamically unstable
patients, uterine tamponade using a Transvaginal ultrasonography is the first-line imaging C 6, 36
Foley catheter or gauze packing can choice for evaluating abnormal uterine bleeding in most
patients.
achieve rapid but temporary control
of blood loss.43 Further emergency The 20-mcg-per-day formulation of the levonorgestrel- A 44, 47
interventions for hemodynamically releasing intrauterine system (Mirena) is more effective
than other medical therapies for reducing heavy men-
unstable patients include intravenous
strual bleeding.
estrogen, dilation and curettage, uter-
ine artery embolization, and, rarely, Hysterectomy is the most effective treatment for reduc- A 44, 47
hysterectomy. Medical therapy (e.g., ing heavy menstrual bleeding.

oral estrogen, combined oral contra- A = consistent, good-quality patient-oriented evidence;​B = inconsistent or limited-quality
ceptives, oral progestins, intravenous patient-oriented evidence;​ C = consensus, disease-oriented evidence, usual practice, expert
opinion, or case series. For information about the SORT evidence rating system, go to https://​
tranexamic acid) is usually adequate www.aafp.org/afpsort.
for treating hemodynamically stable
patients with severe bleeding.
Hysterectomy is the definitive and most effective treat-
NONEMERGENT TREATMENT ment for abnormal uterine bleeding, and it yields a high
A wider range of medical and surgical options are available level of patient satisfaction.44,47,51 A less invasive, lower-risk
for treatment of nonemergent uterine bleeding (Table 4).37-42 surgical option is endometrial ablation, which is as effec-
To avoid surgical risks and preserve fertility, medical man- tive as the levonorgestrel-releasing intrauterine system.47
agement is the first-line approach for most patients.44 Among A variety of ablative techniques are available, and all are
medical therapies, the 20-mcg-per-day formulation of the equivalent in terms of bleeding outcomes and patient satis-
levonorgestrel-releasing intrauterine system (Mirena) is most faction.52 Myomectomy and uterine artery embolization are
effective for decreasing heavy menstrual bleeding (71% to treatment options for leiomyomas, and endometrial polyps
95% reduction in blood loss) and is as effective as hysterec- can be treated with polypectomy. Except for myomectomy
tomy when quality-adjusted life years are considered.39,45-47 and polypectomy, surgical interventions for abnormal uter-
Estrogen-progestin oral contraceptives are effective (35% to ine bleeding are contraindicated in patients who wish to
69% reduction) and can also be used to regulate bleeding in preserve fertility.
patients with ovulatory dysfunction.39,48 Continuous dosing
This article updates previous articles on this topic by Sweet, et
of oral progestins is another effective hormonal treatment al.53;​Albers, et al.54;​and Oriel and Schrager.55
option (87% reduction), but long-term patient satisfaction is
low.39,49 Two effective, well-tolerated, nonhormonal choices Data Sources:​ A PubMed search was completed in Clinical
are oral tranexamic acid (Lysteda; 26% to 54% reduction) and Queries using the key terms abnormal uterine bleeding, heavy
menstrual bleeding, irregular menstrual bleeding, menorrhagia,
nonsteroidal anti-inflammatory drugs (10% to 52% reduc-
metrorrhagia, and dysfunctional uterine bleeding. The search
tion).39,50 Both are taken only when the patient is bleeding, included meta-analyses, randomized controlled trials, clinical
and tranexamic acid has the added benefit of being safe while trials, and reviews. Also searched were the Agency for Health-
the patient is attempting to conceive. care Research and Quality evidence reports, Clinical Evidence,

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 ABNORMAL UTERINE BLEEDING

the Cochrane database, and UpToDate. Search dates:​August 21, 14. Baiocchi G, Manci N, Pazzaglia M, et al. Malignancy in endometrial
2017, and November 10, 2018. polyps:​a 12-year experience. Am J Obstet Gynecol. 2009;​201(5):​
462.e1-462.e4.
15. Taran FA, Stewart EA, Brucker S. Adenomyosis:​epidemiology, risk fac-
The Authors tors, clinical phenotype and surgical and interventional alternatives to
hysterectomy. Geburtshilfe Frauenheilkd. 2013;​73(9):​924-931.
NOAH WOUK, MD, is a family medicine physician at Piedmont
16. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumu-
Health Services, Prospect Hill, N.C., and an adjunct assistant lative incidence of uterine leiomyoma in black and white women:​ultra-
professor in the Department of Family Medicine at the Univer- sound evidence. Am J Obstet Gynecol. 2003;​188(1):​100-107.
sity of North Carolina School of Medicine, Chapel Hill. 17. Wegienka G, Baird DD, Hertz-Picciotto I, et al. Self-reported heavy
bleeding associated with uterine leiomyomata. Obstet Gynecol. 2003;​
MARGARET HELTON, MD, is a professor in the Department 101(3):​431-437.
of Family Medicine at the University of North Carolina School 18. Practice bulletin no. 149:​endometrial cancer. Obstet Gynecol. 2015;​
of Medicine. 125(4):​1006-1026.
19. National Cancer Institute Surveillance, Epidemiology, and End Results
Address correspondence to Noah Wouk, MD, Piedmont Program. Cancer stat facts:​uterine cancer. https://​seer.cancer.gov/
Health Services, 322 Main St., Prospect Hill, NC 27314 (e-mail:​ statfacts/html/corp.html. Accessed November 11, 2017.
woukno@​piedmonthealth.org). Reprints are not available 20. Coulam CB, Annegers JF, Kranz JS. Chronic anovulation syndrome and
from the authors. associated neoplasia. Obstet Gynecol. 1983;​61(4):​403-407.
21. Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Frequency of
inherited bleeding disorders in women with menorrhagia. Lancet. 1998;​
References 351(9101):​485-489.
1. Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evalu- 22. Mikhail S, Varadarajan R, Kouides P. The prevalence of disorders of hae-
ating health-related quality of life, work impairment, and health-care mostasis in adolescents with menorrhagia referred to a haemophilia
costs and utilization in abnormal uterine bleeding. Value Health. 2007;​ treatment centre. Haemophilia. 2007;​1 3(5):​627-632.
10(3):​183-194.
23. Knol HM, Mulder AB, Bogchelman DH, Kluin-Nelemans HC, van der
2. Frick KD, Clark MA, Steinwachs DM, et al.;​STOP-DUB Research Group. Zee AG, Meijer K. The prevalence of underlying bleeding disorders in
Financial and quality-of-life burden of dysfunctional uterine bleeding patients with heavy menstrual bleeding with and without gynecologic
among women agreeing to obtain surgical treatment. Womens Health abnormalities. Am J Obstet Gynecol. 2013;​209(3):​202.e1-202.e7.
Issues. 2009;​19(1):​70-78.
24. Munro MG, Lukes AS;​Abnormal Uterine Bleeding and Underlying

3. Barnard K, Frayne SM, Skinner KM, Sullivan LM. Health status among Hemostatic Disorders Consensus Group. Abnormal uterine bleeding
women with menstrual symptoms. J Womens Health (Larchmt). 2003;​ and underlying hemostatic disorders:​report of a consensus process.
12(9):​911-919. Fertil Steril. 2005;​84(5):​1 335-1337.
4. Côté I, Jacobs P, Cumming DC. Use of health services associated with 25. Vo KT, Grooms L, Klima J, Holland-Hall C, O’Brien SH. Menstrual bleed-
increased menstrual loss in the United States. Am J Obstet Gynecol. ing patterns and prevalence of bleeding disorders in a multidisciplinary
2003;​188(2):​3 43-348. adolescent haematology clinic. Haemophilia. 2013;​19(1):​71-75.
5. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification sys- 26. Committee on Practice Bulletins—Gynecology. Practice bulletin no.

tem (PALM-COEIN) for causes of abnormal uterine bleeding in non- 136:​management of abnormal uterine bleeding associated with ovula-
gravid women of reproductive age. Int J Gynaecol Obstet. 2011;​1 13(1):​ tory dysfunction. Obstet Gynecol. 2013;​1 22(1):​176-185.
3-13.
27. Kouides PA, Conard J, Peyvandi F, Lukes A, Kadir R. Hemostasis and
6. Committee on Practice Bulletins—Gynecology. Practice bulletin no. menstruation:​appropriate investigation for underlying disorders of
128:​diagnosis of abnormal uterine bleeding in reproductive-aged hemostasis in women with excessive menstrual bleeding. Fertil Steril.
women. Obstet Gynecol. 2012;​1 20(1):​197-206. 2005;​84(5):​1 345-1351.
7. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommenda- 28. National Institute for Health and Care Excellence. Heavy menstrual

tions on terminologies and definitions for normal and abnormal uterine bleeding:​assessment and management. Clinical guideline [CG44].
bleeding. Semin Reprod Med. 2011;​29(5):​383-390. Updated August 2016. https://​w ww.nice.org.uk/guidance/cg44.
8. Ahuja SP, Hertweck SP. Overview of bleeding disorders in adoles- Accessed August 31, 2017.
cent females with menorrhagia. J Pediatr Adolesc Gynecol. 2010;​23 29. Zacur HA. Managing an episode of severe or prolonged uterine bleed-
(6 suppl):​S15-S21. ing. UpToDate. August 23, 2016. https://​w ww.uptodate.com/contents/
9. Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, managing-an-episode-of-severe-or-prolonged-uterine-bleeding [sub-
Corton MM. Williams Gynecology. 3rd ed. New York, NY:​McGraw-Hill scription required]. Accessed August 19, 2018.
Education;​ 2016. 30. Marret H, Fauconnier A, Chabbert-Buffet N, et al.;​CNGOF Collège

10. Brenner PF. Differential diagnosis of abnormal uterine bleeding. Am National des Gynécologues et Obstétriciens Français. Clinical practice
J Obstet Gynecol. 1996;​175(3 pt 2):​766-769. guidelines on menorrhagia:​management of abnormal uterine bleed-
1 1. Kaunitz A. Differential diagnosis of genital tract bleeding in women. ing before menopause. Eur J Obstet Gynecol Reprod Biol. 2010;​152(2):​
UpToDate. October 31, 2017. https://​w ww.uptodate.com/contents/ 133-137.
differential-diagnosis-of-genital-tract-bleeding-in-women [subscrip- 31. Warner PE, Critchley HO, Lumsden MA, Campbell-Brown M, Douglas A,
tion required]. Accessed August 19, 2018. Murray GD. Menorrhagia I:​measured blood loss, clinical features, and
1 2. Salim S, Won H, Nesbitt-Hawes E, Campbell N, Abbott J. Diagnosis and outcome in women with heavy periods:​a survey with follow-up data.
management of endometrial polyps:​a critical review of the literature. Am J Obstet Gynecol. 2004;​190(5):​1 216-1223.
J Minim Invasive Gynecol. 2011;​18(5):​569-581. 32. Dilley A, Drews C, Lally C, Austin H, Barnhart E, Evatt B. A survey of
1 3. Lieng M, Istre O, Sandvik L, Qvigstad E. Prevalence, 1-year regression gynecologists concerning menorrhagia:​perceptions of bleeding dis-
rate, and clinical significance of asymptomatic endometrial polyps:​ orders as a possible cause. J Womens Health Gend Based Med. 2002;​
cross-sectional study. J Minim Invasive Gynecol. 2009;​16(4):​465-471. 11(1):​39-44.

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 ABNORMAL UTERINE BLEEDING

33. Braverman PK, Breech L;​Committee on Adolescence. American Acad- 45. Gupta J, Kai J, Middleton L, Pattison H, Gray R, Daniels J;​ECLIPSE Trial
emy of Pediatrics. Clinical report—gynecologic examination for adoles- Collaborative Group. Levonorgestrel intrauterine system versus medi-
cents in the pediatric office setting. Pediatrics. 2010;​1 26(3):​583-590. cal therapy for menorrhagia. N Engl J Med. 2013;​368(2):​1 28-137.
3 4. Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation 46. Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Quality of life and
in hypothyroidism. Clin Endocrinol (Oxf). 1999;​50(5):​655-659. costs of levonorgestrel-releasing intrauterine system or hysterectomy
35. Ronghe R, Gaudoin M. Women with recurrent postmenopausal bleed- in the treatment of menorrhagia:​a 10-year randomized controlled trial.
ing should be re-investigated but are not more likely to have endome- Am J Obstet Gynecol. 2013;​209(6):​535.e1-535.e14.
trial cancer. Menopause Int. 2010;​16(1):​9 -11. 47. Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or pro-
36. Wheeler KC, Goldstein SR. Transvaginal ultrasound for the diagnosis of gestogen-releasing intrauterine systems for heavy menstrual bleeding.
abnormal uterine bleeding. Clin Obstet Gynecol. 2017;​60(1):​1 1-17. Cochrane Database Syst Rev. 2015;​(4):​CD002126.
37. Arias RD, Jain JK, Brucker C, Ross D, Ray A. Changes in bleeding pat- 48. Davis A, Godwin A, Lippman J, Olson W, Kafrissen M. Triphasic norg-
terns with depot medroxyprogesterone acetate subcutaneous injection estimate-ethinyl estradiol for treating dysfunctional uterine bleeding.
104 mg. Contraception. 2006;​74(3):​234-238. Obstet Gynecol. 2000;​96(6):​913-920.
38. Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxy- 49. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkilä A, Walker JJ,
progesterone acetate and combination oral contraceptives for acute Cameron IT. Randomised comparative trial of the levonorgestrel intra-
uterine bleeding:​a randomized controlled trial. Obstet Gynecol. 2006;​ uterine system and norethisterone for treatment of idiopathic menor-
108(4):​924-929. rhagia. Br J Obstet Gynaecol. 1998;​105(6):​592-598.
39. Matteson KA, Rahn DD, Wheeler TL II, et al.;​Society of Gynecologic 50. Hartmann KE, Jerome RN, Lindegren ML, et al.;​Effective Health Care
Surgeons Systematic Review Group. Nonsurgical management of Program;​Agency for Healthcare Research and Quality. Primary care
heavy menstrual bleeding:​a systematic review. Obstet Gynecol. 2013;​ management of abnormal uterine bleeding. Comparative effectiveness
121(3):​632-643. review no. 96. Rockville, Md.:​Agency for Healthcare Research and
Quality;​2013.
40. Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or
extended cycle vs. cyclic use of combined hormonal contraceptives for 51. Cozza G, Pinto A, Giovanale V, et al. Comparative effectiveness and
contraception. Cochrane Database Syst Rev. 2014;​( 7):​CD004695. impact on health-related quality of life of hysterectomy vs. levonorge-
strel intra-uterine system for abnormal uterine bleeding. Eur Rev Med
41. Bradley LD, Gueye NA. The medical management of abnormal uterine
Pharmacol Sci. 2017;​21(9):​2255-2260.
bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016;​
214(1):​31-44. 52. Lethaby A, Penninx J, Hickey M, Garry R, Marjoribanks J. Endome-
trial resection and ablation techniques for heavy menstrual bleeding.
42. ACOG committee opinion no. 557:​management of acute abnormal
Cochrane Database Syst Rev. 2013;​(8):​CD001501.
uterine bleeding in nonpregnant reproductive-aged women. Obstet
Gynecol. 2013;​1 21(4):​891-896. 53. Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP. Evaluation and
management of abnormal uterine bleeding in premenopausal women.
43. James AH, Kouides PA, Abdul-Kadir R, et al. Evaluation and manage-
Am Fam Physician. 2012;​85(1):​35-43.
ment of acute menorrhagia in women with and without underlying
bleeding disorders:​consensus from an international expert panel. Eur 5 4. Albers JR, Hull SK, Wesley RM. Abnormal uterine bleeding. Am Fam Phy-
J Obstet Gynecol Reprod Biol. 2011;​158(2):​1 24-134. sician. 2004;​69(8):​1915-1926.
4 4. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy 55. Oriel KA, Schrager S. Abnormal uterine bleeding. Am Fam Physician.
for heavy menstrual bleeding. Cochrane Database Syst Rev. 2016;​(1):​ 1999;​60(5):​1 371-1380.
CD003855.

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