Abnormal Uterine Bleeding in Nonpregnant Reproductive-Age Patients - Terminology, Evaluation, and Approach To Diagnosis - UpToDate

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Abnormal uterine bleeding in nonpregnant

reproductive-age patients: Terminology, evaluation,
and approach to diagnosis
Author: Andrew M Kaunitz, MD
Section Editors: Robert L Barbieri, MD, Deborah Levine, MD
Deputy Editor: Alana Chakrabarti, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2022. | This topic last updated: May 19, 2022.
INTRODUCTION
Abnormal uterine bleeding (AUB; a term which refers to uterine bleeding of abnormal
quantity, duration, or schedule) is a common gynecologic concern in reproductive-age
females. AUB can be caused by structural uterine pathology (eg, fibroids, endometrial
polyps, adenomyosis, neoplasia) or nonuterine causes (eg, ovulatory dysfunction, disorders
of hemostasis, medications) ( table 1).
The terminology of AUB and evaluation of nonpregnant reproductive-age patients with AUB
will be reviewed here. The terminology of normal menstrual bleeding, an overview of genital
tract bleeding in female patients, and the evaluation of AUB in other patient populations are
reviewed in detail separately.
● Terminology of normal menstrual bleeding (see "Normal menstrual cycle", section on

'Definitions of normal uterine bleeding (menstruation)')
● Causes of genital tract bleeding in female patients (see "Causes of female genital tract
bleeding")
● Bleeding in adolescents (see "Abnormal uterine bleeding in adolescents: Evaluation and

approach to diagnosis")
● Bleeding in perimenopausal patients (see "Clinical manifestations and diagnosis of

menopause")
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● Bleeding in postmenopausal patients (see "Approach to the patient with

postmenopausal uterine bleeding")
● Bleeding in pregnant patients (see "Overview of the etiology and evaluation of vaginal
bleeding in pregnancy")
DEFINITIONS
Standard definitions of normal and abnormal menstrual bleeding are presented in the table
( table 2) [1].
● Abnormalities in frequency ( figure 1)
• Frequent – Frequent menstrual bleeding refers to periods that start at intervals <24
days.
• Infrequent – Infrequent menstrual bleeding refers to periods that start at intervals

>38 days.
• Absent – Absence of menses is either primary (absence of menarche by age 15

years) or secondary (absence of spontaneous menstrual bleeding for six months in
a patient who previously had menstrual bleeding) amenorrhea; these are discussed
in detail separately. (See "Causes of primary amenorrhea" and "Evaluation and
management of primary amenorrhea" and "Epidemiology and causes of secondary
amenorrhea" and "Evaluation and management of secondary amenorrhea".)
● Irregular bleeding ( figure 2) – The definition of irregular bleeding depends on

patient age:
• 18 to 25 years: cycle length variance >9 days

For patients <18 or >45 years, the >9-day definition is also applied, although the
evidence defining normal in these groups is less clear.
● Prolonged menstrual bleeding ( figure 3) is defined as menstrual bleeding

consistently lasting >8 days; this is often, but not always, associated with heavy
menstrual bleeding (HMB).
There is no consensus on the lower limit of normal for the duration of menstrual
bleeding.
● Abnormalities in volume ( figure 4)

• Heavy – For clinical purposes, HMB is defined as a volume that interferes with the
patient's physical, social, emotional, and/or material quality of life [1-3]. It is based
on the patient's perception of increased daily or total monthly volume of menstrual
blood flow, regardless of the duration, frequency, or regularity. It should be noted
that some patients have had HMB "normalized" by family members, friends, or
health care providers, and therefore think their heavy volume is "normal."
Direct measurement of menstrual blood loss, used in the setting of clinical trials,
requires individuals to collect all menstrual products and other blood loss and
submit these for laboratory analysis, usually via the alkaline hematin method, which
is cumbersome and expensive [4-6]. When menstrual blood loss is measured
directly, the definition of HMB is >80 mL menstrual blood loss per cycle. Indirect
assessment of menstrual volume (eg, semiquantitative pictorial blood loss
assessment charts) has been developed [7,8].
• Light – Light menstrual bleeding is uncommon and rarely related to pathology,

although it may be a presenting symptom of cervical stenosis or intrauterine
synechiae. Individuals who express concern about light periods may perceive a
heavy, red bleed as a sign of good health [9].
For research purposes, <5 mL is considered "low volume," a metric that can only be
assessed quantitatively with methods like the alkaline hematin assay [5,10].
● Intermenstrual bleeding ( figure 5) refers to AUB that occurs between well-defined

cyclical menses. The distinction between bleeding and spotting is based on the
patient's need for menstrual product use ( table 3). Intermenstrual bleeding can also
be difficult to distinguish from irregular and/or very frequent menses; thus, care must
be taken before applying this term to patients with these other abnormalities. (See
"Causes of female genital tract bleeding".)
Intermenstrual bleeding can be cyclical or acyclical.
• Cyclical midcycle intermenstrual bleeding – A small amount of bleeding arising

from the endometrium around midcycle occurs in approximately 9 percent of all
reproductive-age females [11]. This is thought to be associated with the midcycle
drop in circulating estradiol levels that occurs just after ovulation [12].
• Acyclical intermenstrual bleeding – Intermenstrual bleeding that is not cyclical or

predictable is typically associated with nonmalignant lesions, such as chronic
cervicitis/endometritis or polyps of the cervix or endometrium or intracavitary
uterine fibroids; postcoital bleeding is a frequent symptom. Less commonly, such
bleeding can be indicative of pathologic process, such as cervical or endometrial

cancer.
Terms not used — There is consensus that some traditional AUB terms should be
abandoned because they are confusing and/or poorly defined [13-15]. These terms include
menorrhagia, metrorrhagia, polymenorrhea, hypermenorrhea, oligomenorrhea, and
dysfunctional uterine bleeding.
ETIOLOGY
The International Federation of Gynecology and Obstetrics (FIGO) classification system

PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy,
ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) is reviewed in detail
separately ( figure 6). (See "Causes of female genital tract bleeding", section on 'Uterine
bleeding'.)
INITIAL EVALUATION OF ALL PATIENTS
In a reproductive-age patient, a single isolated bleeding event that does not result in
hemodynamic instability and occurs in the setting of otherwise normal menstrual cycles may
not require evaluation other than asking the patient to keep a menstrual diary. By contrast,
even a single episode of any postmenopausal bleeding is considered abnormal and requires
evaluation. (See "Approach to the patient with postmenopausal uterine bleeding", section on
'Initial evaluation'.)
Assess hemodynamic stability — Initial triage includes assessment of hemodynamic

stability since hemodynamically unstable patients (eg, tachycardic, hypotensive, orthostatic)
need to be stabilized in the emergency department before proceeding with additional
evaluation of the AUB. (See "Approach to the adult with vaginal bleeding in the emergency
department" and "Managing an episode of acute uterine bleeding", section on 'Managing
hemodynamically unstable patients'.)
Hemodynamically stable patients are typically evaluated in the outpatient setting [16].
However, in young healthy patients, vital signs, including postural changes, may be normal
early in the course of significant bleeding due to compensatory mechanisms [17].
History
Gynecologic and obstetric history
● Menstrual history and bleeding pattern – The following questions can be used to
help elicit the patient's menstrual history and bleeding pattern:
• What was the first day of the last menstrual period and several previous menstrual
periods?
• For how many days does bleeding continue? How many days of full bleeding and
how many days of light bleeding or brown staining does this include?
• Does bleeding occur between menstrual periods?
• If bleeding is irregular, how many bleeding episodes have there been in the past 6
to 12 months? What is the average time from the first day of one bleeding episode
to the next?
• Is the bleeding associated with dysmenorrhea or dyspareunia (ie, suggestive of

endometriosis and/or adenomyosis)?
• How heavy is the bleeding? Questions that help to characterize the volume of
uterine bleeding are shown in the table ( table 4).
A patient may have strong concerns over changes in menstrual blood loss; however,
patient self-reports are, in general, inaccurate indicators of the quantity of blood
lost at menses, and pathologic assessment of the uterus often shows no evidence of
disease, despite patient symptoms [4,18-22]. In one study including over 200
patients reporting heavy periods, only one-third of patients had objectively
documented excessive bleeding (ie, >80 mL blood loss per cycle) [23].
• Is the patient certain that the bleeding is from the vagina?
- Does the patient see the blood in the toilet only during or after either urination
or defecation?
- Does the patient see the bleeding only when wiping with toilet tissue? If so, has
the patient tried to separately dab the urethra, vagina, and anus with toilet
tissue to check the source of the bleeding?
- If the patient uses a pad, on what part of the pad is blood visible? If the patient
uses a tampon, is bleeding visible while a tampon is in the vagina?
In general, if the bleeding occurs solely with urination or defecation and the pattern
of bleeding or findings on physical examination are consistent with a urinary or
gastrointestinal tract source, this should be the focus of further evaluation. Changes
in bladder or bowel function may also suggest a mass effect from an enlarged
fibroid uterus or a neoplasm. Evaluation of hematuria and rectal bleeding is

discussed in detail separately. (See "Etiology and evaluation of hematuria in adults"
and "Approach to minimal bright red blood per rectum in adults".)
• Were there precipitating factors, such as trauma, intercourse, or a procedure?

Bleeding related to trauma or intercourse suggests a vaginal or cervical source of
bleeding (eg, cervical dysplasia, cervicitis, vulvovaginal atrophy, cervical polyp),
while bleeding after a procedure (eg, pregnancy termination, intrauterine device
[IUD] placement) may suggest a uterine source of bleeding. (See "Postcoital
bleeding in females".)
● Sexual history – A sexual history helps to determine whether the patient might be
pregnant, as pregnancy is a common cause of uterine bleeding; however, a pregnancy
test is generally also performed. (See 'Pregnancy test' below.)
A sexual history may also help determine the patient's risk for sexually transmitted
infections (eg, Chlamydia trachomatis, Neisseria gonorrhoeae, trichomonas, herpes
simplex), which can cause cervicitis and present with cervical bleeding. Patients at risk
for sexually transmitted infections should be asked if they have lower abdominal pain,
fever, and/or vaginal discharge, all which suggest pelvic infection (eg, pelvic
inflammatory disease [PID], endometritis). In one series, 15 percent of participants with
upper genital tract infection presented with AUB [24]. (See "Clinical manifestations and
diagnosis of Chlamydia trachomatis infections" and "Clinical manifestations and
diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and "Acute
cervicitis" and "Endometritis unrelated to pregnancy" and "Pelvic inflammatory disease:
Clinical manifestations and diagnosis".)
● History of obstetric or gynecologic surgery – A history of obstetric or gynecologic

surgery may suggest an underlying disorder that can be associated with AUB:
- A prior cesarean birth can result in a cesarean scar defect (particularly if a

patient has had multiple cesarean births)
- Past myomectomy suggests the possibility of recurrent or persistent uterine

fibroids
- Past excisional cervical procedures performed for diagnosis or management of

cervical intraepithelial neoplasia suggest the possibility of recurrent or
persistent cervical neoplasia
- Rarely, uterine surgery can result in an arteriovenous malformation (also

referred to as enhanced myometrial vascularity)
These entities are discussed in more detail below. (See 'Intermenstrual bleeding' below
and 'Heavy menstrual bleeding' below.)
● Contraceptive history – Many contraceptives can cause AUB; the pattern varies
depending on the specific contraceptive. Patients using combined estrogen-progestin
contraceptives or progestin-only contraceptives may develop unscheduled bleeding,
decreased menstrual flow, or amenorrhea. The copper IUD increases menstrual flow
while some types of levonorgestrel IUDs (eg, LNG 52; Mirena, Liletta) are associated
with decreased menstrual flow and amenorrhea. (See 'Secondary evaluation' below and
"Evaluation and management of unscheduled bleeding in individuals using hormonal
contraception".)
● Risk factors for endometrial cancer – Endometrial hyperplasia and carcinoma often
present with AUB ( table 5). (See 'Based on risk factors for endometrial cancer' below
and 'Endometrial sampling: Choice of modality' below.)
Medical history — The review of systems and medical history may reveal a condition or
medication associated with AUB. Patients should be asked about a family history of bleeding
disorders, thyroid disease, and hyperprolactinemia. They also should be asked about
associated symptoms including bruising or petechiae, galactorrhea, heat or cold intolerance,
and about symptoms suggestive of hypothalamic dysfunction (eg, recent illness, stress,
excessive exercise, eating disorder).
● Medications that can cause AUB include anticoagulants, which may result in heavy or
prolonged uterine bleeding, and medications that cause hyperprolactinemia, which can
result in oligomenorrhea or amenorrhea ( table 6). (See 'Secondary evaluation'
below.)
● Bleeding disorders – Bleeding disorders may present at menarche or later during a

patient's reproductive years. The prevalence of von Willebrand disease (an inherited
bleeding disorder), which is approximately 1 percent in the general population, is
substantially higher among patients with chronic heavy uterine bleeding [25]. Other
bleeding disorders associated with heavy menstrual bleeding (HMB) include immune
thrombocytopenia, platelet function defect, or an acquired bleeding diathesis (eg,
hematologic malignancy, liver or renal disease, prescription or nonprescription drugs) (
table 7) [25-31]. (See "Causes of female genital tract bleeding", section on
'Coagulopathy (AUB-C)' and "Approach to the adult with a suspected bleeding
disorder", section on 'Patient history' and "Clinical presentation and diagnosis of von
Willebrand disease", section on 'Changes with aging and pregnancy'.)
Indications for coagulation testing are discussed below. (See 'Heavy menstrual
bleeding' below.)
● Endocrine disorders – Thyroid disease is often associated with oligomenorrhea or

amenorrhea; although traditionally thought to be a common cause of HMB, available
data suggest that it is an uncommon etiology of this bleeding pattern [32,33]. (See
"Clinical manifestations of hypothyroidism", section on 'Reproductive abnormalities'.)
Hyperprolactinemia is also associated with amenorrhea. (See 'Heavy menstrual

bleeding' below and 'Based on bleeding pattern' below.)
● Other – Patients with chronic medical conditions (eg, type 1 diabetes mellitus, celiac
disease, chronic kidney disease [34-37]) may develop secondary amenorrhea when it is
severe enough to result in a decrease in hypothalamic gonadotropin-releasing
hormone (GnRH) secretion and/or when it is associated with nutritional deficiencies.
(See 'Amenorrhea' below and "Epidemiology and causes of secondary amenorrhea",
section on 'Systemic illness'.)
Physical examination — The goal of the physical examination is to look for signs of

systemic illness, such as fever, ecchymoses, an enlarged thyroid gland, or evidence of
hyperandrogenism (eg, hirsutism, acne, clitoromegaly, male pattern balding). Acanthosis
nigricans may be seen in patients with polycystic ovary syndrome (PCOS). Galactorrhea
(bilateral milky nipple discharge unrelated to pregnancy or breastfeeding) suggests the
presence of hyperprolactinemia.
A complete pelvic examination should be performed, with a particular focus on:
● Potential sites of bleeding from the vulva, vagina, cervix, urethra, anus, or perineum (
table 1). Any abnormal finding should be noted (eg, mass, laceration, ulceration,
friable area, vaginal or cervical discharge, foreign body, urethral caruncle, hemorrhoid)
as possible evidence of a nonuterine source of bleeding.
● Current uterine bleeding – The presence and volume of bleeding from the cervical os
and blood or blood clots in the vaginal vault should be noted.
● Size and contour of the uterus – An enlarged uterus may be due to pregnancy, uterine
leiomyomas, adenomyosis, or uterine malignancy. Limited uterine mobility should be
noted, if present; this finding suggests that pelvic adhesions (from prior infection,
surgery, or endometriosis) or a pelvic mass is present. A boggy, globular, tender uterus
may be noted in patients with adenomyosis. Uterine tenderness is often present in
patients with PID but is not consistently found in those with chronic endometritis. (See
"Uterine adenomyosis", section on 'Pelvic examination' and "Endometriosis: Clinical
features, evaluation, and diagnosis", section on 'Physical examination' and
"Endometritis unrelated to pregnancy", section on 'Clinical manifestations and
diagnosis'.)
● Presence of an adnexal mass or tenderness – This may reflect a tubo-ovarian abscess

which may be associated with endometritis. Rarely, an ovarian neoplasm (eg, granulosa
cell tumor) may be hormonally active and cause endometrial neoplasia.
Pregnancy test — Pregnancy should be excluded in all reproductive-age patients with AUB.

Pregnancy testing should be performed even in patients with recent vaginal bleeding since
this may represent bleeding during pregnancy rather than menses. It should also be
performed in patients who report no sexual activity and in those who report use of
contraception.
A urine human chorionic gonadotropin (hCG) test may be performed as an initial test in a
clinic or urgent care setting since these results are available quickly.
● If the urine test is negative but the clinician continues to suspect early pregnancy may
be present, serum hCG should be measured. A serum hCG assay can detect a
pregnancy by one week after conception compared with only 50 percent of urine hCG
tests by 11 days (and 98 percent by 14 days) [38-40].
● If either the urine or serum test is positive, patients should be evaluated for pregnancy-
related causes of bleeding. Serial quantitative serum hCG testing is appropriate if
ectopic pregnancy or spontaneous abortion is suspected. Gestational trophoblastic
disease, which in some cases presents weeks to years after a pregnancy, is also
associated with AUB and a positive pregnancy test. (See "Overview of the etiology and
evaluation of vaginal bleeding in pregnancy" and "Hydatidiform mole: Epidemiology,
clinical features, and diagnosis".)
Diagnosis of pregnancy is discussed in detail separately. (See "Clinical manifestations and

diagnosis of early pregnancy".)
Role of ultrasound — While many patients will ultimately need an ultrasound as part of the
secondary evaluation, we typically avoid routinely ordering it as part of the initial evaluation
in all patients. (See 'Secondary evaluation' below.)
SECONDARY EVALUATION
Additional evaluation is selective and depends on information obtained during the history
and physical examination ( table 8). (See 'History' above and 'Physical examination' above.)
Based on bleeding pattern
Heavy menstrual bleeding — Based on current terminology, heavy menstrual bleeding

(HMB; regular bleeding that is heavy or prolonged) refers only to cyclic (ovulatory) menses
[41]. (See 'Definitions' above.)
Further testing is guided by findings on history and physical examination ( table 9).
Patients with a TCu-380A (ParaGard) intrauterine device (IUD) may have iatrogenic HMB and
not require further evaluation; this is discussed in detail separately. (See "Intrauterine
contraception: Management of side effects and complications", section on 'Continued
bleeding and cramping'.)
● Imaging is typically performed to assess for the following (see 'Imaging: Choice of
modality' below):
• Uterine fibroids (an enlarged uterus or discrete mass may be palpated on

examination); HMB associated with uterine leiomyomas is most likely to occur with
submucosal leiomyomas, but leiomyomas at other sites may also cause AUB. (See
"Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and
natural history".)
• Adenomyosis (a boggy uterus may be palpated on examination or the patient may

report a history of dysmenorrhea). (See "Uterine adenomyosis".)
• Endometrial polyps (in the absence of a prolapsed polyp, physical examination is

usually normal). (See "Endometrial polyps".)
• Uterine arteriovenous malformation (also referred to as congenital or acquired

enhanced myometrial vascularity) is an uncommon cause of HMB but should be
suspected when an invasive procedure (eg, dilation and curettage) for unexplained
bleeding aggravates the bleeding [42-44]. Acquired uterine arteriovenous
malformations typically occur after failed intrauterine pregnancies, medical or
surgical induced abortion, uterine curettage, cesarean delivery, and in patients with
cesarean scar pregnancies [45].
● Laboratory tests – A complete blood count is performed for all patients with HMB to
assess for anemia; assessing a ferritin level can identify patients who, although not
currently anemic, have depleted iron stores. (See "Causes and diagnosis of iron
deficiency and iron deficiency anemia in adults", section on 'Diagnostic evaluation'.)
An elevated white blood cell count may suggest an infection (eg, pelvic inflammatory
disease [PID], acute endometritis after a gynecologic procedure) or, uncommonly,
leukemia as a cause of HMB [31]. By contrast, the white blood cell count is typically
normal in chronic endometritis. (See "Endometritis unrelated to pregnancy" and "Pelvic
inflammatory disease: Clinical manifestations and diagnosis", section on 'Point-of-care
and laboratory tests'.)
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Additional laboratories are typically performed for patients with HMB and concerns for
any of the following:
• Bleeding disorder – Patients with symptoms, risk factors (eg, anticoagulant therapy,
thrombocytopenia, liver or renal disease), or a family history of a bleeding disorder
require further evaluation. This is discussed separately. (See "Approach to the adult
with a suspected bleeding disorder", section on 'Laboratory evaluation'.)
Patients who are taking warfarin should have coagulation parameters (eg,
international normalized ratio [INR]) assessed to see if the effect is within the
therapeutic window. (See "Approach to the adult with a suspected bleeding
disorder", section on 'Medication use'.)
• Thyroid disease – A serum thyroid-stimulating hormone (TSH) level should be

performed if thyroid disease is suspected. (See "Diagnosis of and screening for
hypothyroidism in nonpregnant adults" and "Diagnosis of and screening for
hypothyroidism in nonpregnant adults", section on 'Diagnosis'.)
● Endometrial sampling is typically performed for select patients with HMB with risk
factors, or suspicion, for uterine malignancy ( table 5 and table 10) (see 'Based on
risk factors for endometrial cancer' below and 'Endometrial sampling: Choice of
modality' below). Endometrial hyperplasia or carcinoma or, rarely, uterine sarcoma may
be associated with HMB, but the typical bleeding pattern for these conditions is
postmenopausal bleeding. (See "Endometrial sampling procedures", section on
'Indications'.)
Intermenstrual bleeding — Intermenstrual uterine bleeding may be related to a variety of

etiologies, including abnormalities of the cervix (eg, cervical polyps, cervicitis, ectropion,
cervical cancer), uterus (eg, chronic endometritis, endometrial polyps), or unscheduled
bleeding due to a contraceptive method. These conditions are discussed separately. (See
"Causes of female genital tract bleeding".)
Further testing is guided by findings on history and physical examination ( table 11).
● Imaging is typically performed for patients with intermenstrual bleeding to assess for
the following (see 'Imaging: Choice of modality' below):
• Endometrial polyps (in the absence of a prolapsed polyp, physical examination is

usually normal). (See "Endometrial polyps".)
• Cesarean scar defect. Approximately two-thirds of patients who have had one or (in
particular) multiple cesarean births may have a cesarean scar defect, and
approximately one-third of patients with this condition experience cyclical,
postmenstrual bleeding [46]. The mechanism by which this occurs is discussed in

detail separately.
● Endometrial sampling is typically performed for patients with intermenstrual bleeding

and concerns for uterine malignancy ( table 5 and table 10). (See 'Based on risk
factors for endometrial cancer' below and 'Endometrial sampling: Choice of modality'
below.)
Endometrial sampling may also be performed in patients with intermenstrual bleeding

in whom chronic endometritis is suspected. (See 'History' above.)
● Laboratory tests are generally not required for patients with intermenstrual bleeding.
Irregular bleeding — Irregular uterine bleeding is most commonly associated with

ovulatory dysfunction (AUB-O) ( table 12) and typically occurs at the extremes of
reproductive age (ie, postmenarchal, perimenopausal) (see 'Definitions' above). Patients may
either have anovulation or oligo-ovulation, in which they shift between ovulatory cycles and
anovulation. Bleeding is typically characterized by phases of no bleeding that may last for
two or more months and other phases with either spotting or episodes of heavy bleeding.
Molimina symptoms (eg, breast tenderness, bloating, fatigue) are typically absent.
While further evaluation is not generally required to confirm ovulatory dysfunction, it is

helpful in identifying the cause of bleeding so that it can be treated, and adverse
consequences can be prevented. Further evaluation may include:
● Laboratory tests
• Thyroid function tests – A TSH level should be measured to exclude thyroid disease
as a cause of anovulation. (See 'Heavy menstrual bleeding' above.)
• Prolactin level – A prolactin level should be measured in patients who complain of

anovulatory bleeding, amenorrhea, or galactorrhea, or are taking medications that
can cause hyperprolactinemia ( table 6). (See "Clinical manifestations and
evaluation of hyperprolactinemia".)
• Androgen levels – Serum androgens should be measured in patients with irregular

bleeding and signs of androgen excess. Hirsutism (excessive male-pattern facial and
body hair) is far more common than virilization (deepening of the voice, temporal
balding, breast atrophy, changes toward a male body habitus, and/or clitoromegaly)
[47]. Polycystic ovarian syndrome (PCOS) is the most common cause of hirsutism
and amenorrhea or anovulatory bleeding. However, clinical manifestations of
hyperandrogenism may also be seen in patients with congenital adrenal
hyperplasia. If virilization is present, a more severe androgen excess should be
suspected and the patient should be evaluated for an androgen-secreting tumor of

the adrenal gland or ovary. (See "Pathophysiology and causes of hirsutism".)
• Follicle-stimulating hormone (FSH) or luteinizing hormone (LH) – FSH and LH are

released by the pituitary gland. If premature ovarian insufficiency is suspected, a
serum FSH should be performed. For patients with suspected hypothalamic
dysfunction (due to poor nutrition or intense exercise), FSH, LH, and estradiol
should be assessed. (See "Clinical manifestations and diagnosis of spontaneous
primary ovarian insufficiency (premature ovarian failure)", section on 'Diagnosis'.)
• Estrogen levels – As with FSH, if premature ovarian insufficiency is suspected, a

serum estradiol assessment should be performed. Estrogen excess due to an
estrogen-secreting ovarian tumor is a rare etiology of AUB but should be considered
if an adnexal mass is present and if other etiologies have been excluded. (See "Sex
cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in
adults".)
● Endometrial sampling is typically performed for patients with irregular bleeding that
has been present for six months or more given their increased risk of endometrial
hyperplasia/neoplasia ( table 5 and table 10). This is discussed in more detail
below. (See 'Based on risk factors for endometrial cancer' below and 'Endometrial
sampling: Choice of modality' below.)
● Imaging – Imaging is generally not required for patients with irregular bleeding due to
ovulatory dysfunction. This is discussed in detail separately. (See "Diagnosis of
polycystic ovary syndrome in adults", section on 'Transvaginal ultrasound'.)
Amenorrhea — Amenorrhea refers to absence of bleeding for at least three usual cycle

lengths. Amenorrhea may be primary (ie, menarche is absent) or secondary (ie, menses
cease after menarche). The evaluation of amenorrhea is discussed separately. (See
"Evaluation and management of primary amenorrhea" and "Evaluation and management of
secondary amenorrhea".)
Decreased volume — Patients sometimes report periods that are regular but have become
unusually light or of short duration. Patients using hormonal contraception (including
levonorgestrel IUD) often will experience decreased menstrual blood loss; this is expected
and does not require further evaluation. (See "Combined estrogen-progestin oral
contraceptives: Patient selection, counseling, and use", section on 'Advantages'.)
Causes of decreased menstrual volume that do require further evaluation include partial
cervical stenosis or Asherman syndrome; these are discussed separately. (See "Intrauterine
adhesions: Clinical manifestation and diagnosis".)
Regular menses with increased frequency — During the menopausal transition, patients

may experience a decrease in the interval between menses. Cycle length that has shortened,
but not to less than every 24 days, may be normal during this phase. If the bleeding is also
irregular, heavy, or occurs less often than every 24 days, other etiologies should be
investigated. (See 'Irregular bleeding' above and 'Heavy menstrual bleeding' above.)
Based on risk factors for endometrial cancer — Patients with AUB and obesity or other
risk factors for endometrial cancer ( table 5) should be evaluated with endometrial
sampling.
Indications for endometrial sampling in patients of reproductive age with AUB vary by age
group ( table 10):
● Age 45 years to menopause – Bleeding that is frequent, heavy, prolonged, or occurs

between cycles (ie, intermenstrual bleeding) ( table 2).
● Age <45 years – Bleeding that is persistent (usually defined as six months or more [48])
and occurs in the setting of one of the following: a history of unopposed estrogen
exposure (eg, obesity, chronic ovulatory dysfunction) [49,50], failed medical
management of the bleeding, or in patients at high risk of endometrial cancer (eg,
tamoxifen therapy, Lynch or Cowden syndrome).
Use of 45 years old as the threshold for increased concern regarding endometrial
neoplasia is supported by evidence that the risk of endometrial hyperplasia and
carcinoma increases with advancing age: 0.05, 6, and 19 percent of cases of
endometrial cancer occur in patients ages 15 to 19, 25 to 44, and 45 to 54 years,
respectively [51-54]. This age threshold is also consistent with American College of
Obstetricians and Gynecologists (ACOG) guidelines [49,55]. (See "Endometrial
hyperplasia: Clinical features, diagnosis, and differential diagnosis", section on
'Epidemiology' and "Endometrial carcinoma: Epidemiology, risk factors, and
prevention", section on 'Epidemiology'.)
Patients with obesity and AUB are at an increased risk of endometrial neoplasia regardless
of age. This is because patients with obesity have high levels of endogenous estrogen due to
the conversion of androstenedione to estrone and the aromatization of androgens to
estradiol in adipose tissue, and this becomes a source of endogenous unopposed estrogen
in the setting of ovulatory dysfunction. In one retrospective study including over 900
premenopausal patients with AUB (average age 42 to 44 years), those with a body mass
index ≥30 kg/m2 were fourfold more likely to develop complex endometrial hyperplasia (with
or without atypia) or endometrial carcinoma than other patients [56]. (See "Endometrial
carcinoma: Epidemiology, risk factors, and prevention", section on 'Obesity'.)
SUBSEQUENT EVALUATION FOR SELECT PATIENTS
In patients with AUB in whom the initial and secondary evaluation are normal, hormonal
therapy (eg, combination estrogen-progestin contraceptives, levonorgestrel intrauterine
device [IUD]) is often used as initial empiric treatment. (See "Abnormal uterine bleeding in
nonpregnant reproductive-age patients: Management", section on 'Preferred approach for
most patients'.)
In addition, the possibility of concurrent factors should also be considered. For example,
patients with uterine fibroids or adenomyosis may not present for care until anovulation
associated with perimenopause causes heavy, irregular bleeding; a patient with a fibroid
uterus may also have a defect of hemostasis that is the primary reason for the heavy
bleeding; a patient with a fibroid uterus may experience bleeding from an endometrial or
endocervical malignancy unrelated to the fibroid itself. Therefore, several potential etiologies
often need to be investigated and, if a cause of AUB is determined but bleeding persists
despite treatment, the patient should be evaluated for additional etiologies.
SPECIAL CONSIDERATIONS
Endometrial sampling: Choice of modality — Endometrial sampling is typically performed

as an office biopsy, but dilation and curettage or hysteroscopically-directed biopsy may be
performed if bleeding persists after a normal endometrial biopsy or if there are other
indications for an operative procedure. (See "Endometrial sampling procedures" and
"Overview of the evaluation of the endometrium for malignant or premalignant disease".)
While transvaginal ultrasound can provide useful information regarding structural causes of
AUB (eg, fibroids, adenomyosis, polyps), measurement of endometrial thickness is not used
as an alternative to endometrial sampling for the evaluation of endometrial neoplasia in
reproductive-age patients as major variation in endometrial thickness occurs during the
normal menstrual cycle. (See "Overview of the evaluation of the endometrium for malignant
or premalignant disease", section on 'Premenopausal patients with abnormal bleeding'.)
Imaging: Choice of modality — The choice of pelvic imaging is based on the clinician's

judgment, depending on patient age, history, and symptoms.
● Pelvic ultrasound – Pelvic ultrasound is the first-line imaging study in patients with
AUB. Transvaginal examination should be performed, unless there is a reason to not
perform the vaginal study (eg, patient declines). Transabdominal sonography should
also be performed if transvaginal imaging does not allow adequate assessment of the
uterus or adnexa or if a large pelvic mass is present.
Ultrasound is effective at characterizing anatomic as well as vascular uterine pathology

and adnexal lesions [45]. As noted above, assessment of endometrial thickness is often
not useful in premenopausal patients. (See 'Endometrial sampling: Choice of modality'
above.)
● If intracavitary pathology (lesions that protrude into the uterine cavity [ie, endometrial
polyps, submucosal myomas, intramural myomas with an intracavitary component]) is
suspected based upon the initial ultrasound, the patient may be evaluated with either
saline infusion sonohysterography or hysteroscopy.
• Saline infusion sonography (SIS) – SIS (also called sonohysterography) is a

technique in which sterile saline is instilled into the endometrial cavity and a
transvaginal ultrasound examination is performed [57]. This procedure allows for an
architectural evaluation of the uterine cavity to detect lesions (eg, polyps or small
submucous fibroids) that may be missed or poorly defined by transvaginal
sonography alone ( image 1). SIS is also useful in evaluating AUB associated with
cesarean scar defects [58]. (See "Saline infusion sonohysterography".)
• Hysteroscopy – Hysteroscopy provides direct visualization of the endometrial cavity.

Diagnostic hysteroscopy can be performed in an office setting. In an operative
setting, hysteroscopy allows targeted biopsy or excision of lesions identified during
the procedure [59,60]. (See "Overview of hysteroscopy".)
We suggest SIS for most patients for intracavitary evaluation. Both SIS and
hysteroscopy are effective tests for diagnosing endometrial polyps and submucosal
leiomyoma [61], while ultrasound alone has limited sensitivity and specificity for the
characterization of these lesions [62,63]. Compared with hysteroscopy, the major
advantage of SIS is that it can assess the depth of extension of leiomyomas into the
myometrium or serosal surface ( image 2). Some fibroids appear to be submucosal
at hysteroscopy but are actually intramural with a component that protrudes into the
uterine cavity. This information and the ability to identify fibroids at other sites (
figure 7 and figure 8) can help surgical planning. Some data also suggest that SIS
is less painful than office hysteroscopy [62,64]. SIS also is able to identify asymmetric or
focal endometrial thickening, a potentially important marker of endometrial neoplasia (
image 3) [61].
Advantages of hysteroscopy are that office hysteroscopy may offer patients greater
convenience, particularly if it can be performed at the same visit as the initial
evaluation. Operative hysteroscopy, including resection of endometrial polyps or
submucosal fibroids, is not typically available in an office setting and therefore, in most
settings, is not part of the initial evaluation of AUB in the United States.
Factors such as convenience, availability of equipment and trained personnel, and cost
of SIS and hysteroscopy vary in different clinical settings, and these factors often
influence the choice of study. Of note, the United Kingdom National Institute for Health
and Care Excellence (NICE) guidelines regarding heavy menstrual bleeding (HMB)
suggest that for patients with AUB and suspected submucosal fibroids, polyps or
endometrial pathology outpatient hysteroscopy be performed as initial evaluation [65].
● Other – Magnetic resonance imaging (MRI) should be used for pelvic assessment only
as a follow-up imaging test when additional information (eg, further characterization of
a lesion) that is not available on ultrasound could potentially impact clinical
management.
Computed tomography (CT) has no role in routine pelvic assessment of AUB. (See
"Overview of the evaluation of the endometrium for malignant or premalignant
disease", section on 'Other'.)
WHEN TO REFER
Referral to a gynecologist is appropriate for patients who have heavy bleeding, severe
anemia, persistent bleeding despite treatment, if there is suspicion of malignancy, or if
surgery is required. Referral to a gynecologist is also appropriate if the primary care clinician
is not comfortable performing endometrial sampling or placing an intrauterine device (IUD;
for treatment of AUB).
If gynecologic malignancy is suspected, or if a patient with AUB would like to conceive,

referral to a gynecologic oncologist or a reproductive endocrinologist and infertility
specialist may be appropriate. In addition, if saline infusion sonography (SIS) or
hysteroscopy is indicated and the initial clinician lacks the experience or resources to
perform these procedures, referral to a gynecologist with the needed experience and
equipment is appropriate.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Abnormal uterine
bleeding" and "Society guideline links: Hemophilia A and B".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Heavy periods (The Basics)")
● Beyond the Basics topics (see "Patient education: Abnormal uterine bleeding (Beyond
the Basics)" and "Patient education: Heavy or prolonged menstrual bleeding
(menorrhagia) (Beyond the Basics)" and "Patient education: Absent or irregular periods
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Definitions and etiology
• Standard definitions of abnormal menstrual bleeding (AUB) are presented in the

table ( table 2). (See 'Definitions' above.)
• Causes of AUB include structural uterine pathology (eg, fibroids, endometrial

polyps, adenomyosis, neoplasia), infections (eg, endometritis), or nonuterine causes
(eg, ovulatory dysfunction, disorders of hemostasis, medications) ( table 1 and
figure 6). (See 'Etiology' above and "Causes of female genital tract bleeding",
section on 'Uterine bleeding'.)
● Initial evaluation of all patients – All patients with AUB should have a complete
history and physical examination. Information should be obtained on the frequency,
duration, and volume of AUB, as well as the presence of associated symptoms and
precipitating factors. Pregnancy should be excluded in all patients. Patients with acute
bleeding should be evaluated in the emergency department. (See 'Initial evaluation of
all patients' above.)
● Secondary evaluation – Further evaluation is determined by the pattern, severity, and

etiology of the bleeding ( table 8). (See 'Secondary evaluation' above.)
• HMB – Patients with heavy menstrual bleeding (HMB) often undergo pelvic imaging
to assess for structural lesions (eg, uterine fibroid, adenomyosis, endometrial
polyp), a complete blood count (to assess for anemia, thrombocytopenia), and
measurement of ferritin level (to assess iron stores). Additional laboratories are
ordered if a bleeding disorder (eg, von Willebrand disease) or endocrine disorder
(eg, hypothyroidism) is suspected. Endometrial sampling is performed for patients
with obesity or other risk factors for endometrial hyperplasia or carcinoma. (See
'Heavy menstrual bleeding' above.)
• Intermenstrual bleeding – Patients with intermenstrual bleeding also often

undergo pelvic imaging (to assess for an endometrial polyp or cesarean scar defect)
and endometrial sampling (to assess for malignancy or endometritis). (See
'Intermenstrual bleeding' above.)
• Irregular bleeding – Patients with irregular bleeding often have ovulatory

dysfunction. Laboratories may be ordered to evaluate for thyroid disease,
hyperprolactinemia, or premature ovarian insufficiency. Endometrial sampling
should be performed for persistent symptoms (six months or more) given the
increased risk of endometrial hyperplasia/neoplasia. (See 'Irregular bleeding'
above.)
• Indications for endometrial sampling – Endometrial sampling should be

performed in nonpregnant patients with any bleeding pattern if obesity or other
risk factors for endometrial hyperplasia or cancer are present. Indications for
endometrial sampling vary by age group ( table 5 and table 10). (See 'Based on
risk factors for endometrial cancer' above.)
● Causes of iatrogenic bleeding – Many contraceptives (eg, combined oral

contraceptives, intrauterine device [IUD; both hormonal and nonhormonal types]) can
cause iatrogenic AUB, which in this setting may not require further evaluation. (See
'History' above.)
● Imaging – Pelvic ultrasound (typically transvaginal) is the first-line imaging study in

most patients. Ultrasound may be combined with either saline infusion sonography
(SIS) or hysteroscopy to provide information about lesions that protrude into the
endometrial cavity (eg, endometrial polyps, submucosal myomas, intramural myomas
with an intracavitary component). (See 'Imaging: Choice of modality' above.)
ACKNOWLEDGMENT
The UpToDate editorial staff acknowledges Annekathryn Goodman, MD, MPH, MS, who
contributed to earlier versions of this topic review.
Use of UpToDate is subject to the Terms of Use.
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Topic 3263 Version 50.0
GRAPHICS
Causes of abnormal genital tract bleeding in females
Genital tract disorders Trauma
Uterus Sexual intercourse
Benign conditions: Sexual abuse
Endometrial polyps Foreign bodies (including intrauterine

device)
Endometrial hyperplasia
Pelvic trauma (eg, motor vehicle accident)
Adenomyosis
Straddle injuries
Leiomyomas (fibroids)
Cesarean scar defect (prior cesarean
Arteriovenous malformation (also
delivery)
referred to as enhanced myometrial
vascularity) Drugs
Cancer: Contraception:
Endometrial adenocarcinoma Hormonal contraceptives
Sarcoma Intrauterine devices
Infection: Postmenopausal hormone therapy
Pelvic inflammatory disease Anticoagulants
Endometritis Tamoxifen
Ovulatory dysfunction Corticosteroids
Cervix Chemotherapy
Benign conditions: Phenytoin
Cervical polyps Antipsychotic drugs
Ectropion Antibiotics (eg, due to toxic epidermal

necrolysis or Stevens-Johnson syndrome)
Endometriosis
Systemic disease
Cancer:
Invasive carcinoma Diseases involving the vulva:
Crohn disease
Metastatic (uterus, choriocarcinoma)
Infection: Behçet syndrome
Cervicitis Pemphigoid
Pemphigus
Vulva
Erosive lichen planus
Benign conditions:
Lymphoma
Skin tags
Bleeding disorders:
Sebaceous cysts
von Willebrand disease
Condylomata Thrombocytopenia or platelet

dysfunction
Angiokeratoma
Acute leukemia
Cancer
Some coagulation factor deficiencies
Vagina
Advanced liver disease
Benign conditions:
Thyroid disease
Gartner duct cysts
Polycystic ovary syndrome
Polyps
Cushing syndrome
Adenosis (aberrant glandular tissue)
Hormone-secreting adrenal and ovarian
Cancer
tumors
Vaginitis/infection:
Renal disease
Bacterial vaginosis
Emotional or physical stress
Sexually transmitted infections
Smoking
Atrophic vaginitis
Excessive exercise
Upper genital tract disease
Diseases not affecting the genital
Pelvic inflammatory disease tract
Fallopian tube cancer Urethritis
Ovarian cancer Bladder cancer
Pregnancy complications Urinary tract infection
Colorectal cancer
Inflammatory bowel disease
Hemorrhoids
Other
Endometriosis
Graphic 74527 Version 13.0
Normal menstruation parameters
Parameter Normal Abnormal
Frequency ≥24 and ≤38 days Absent (no bleeding):

amenorrhea
Frequent (<24 days)
Infrequent (>38 days)
Duration ≤8 days Prolonged (>8 days)
Regularity Regular: shortest to longest Irregular: shortest to longest

cycle variation: ≤7 to 9 days* cycle variation: ≥10 days
Flow volume (patient Patient considers normal Patient considers light

determined)
Patient considers heavy
Intermenstrual bleeding None Random

(bleeding between cyclically
Cyclic (predictable):
regular onset of menses)
Early cycle
Mid cycle
Late cycle
Unscheduled bleeding on Not applicable for patients not Present

progestin±estrogen gonadal on gonadal steroid medication
steroids (contraceptive pills,
rings, patches, IUDs, or None (for patients on gonadal
injections) steroid medication)
IUDs: intrauterine contraceptive devices.
* Normal variation depends on age; these data are calculated excluding short and long outliers.
Data from:
1. Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead to international agreement on
terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007; 87:466.
2. Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international agreement on terminologies and
definitions used to describe abnormalities of menstrual bleeding? Hum Reprod 2007; 22:635.
3. Fraser IS, Munro MG, Broder M, Critchley HO. International recommendations on terminologies and definitions
for normal and abnormal uterine bleeding. Semin Reprod Med 2011.
Frequency of menses
The normal frequency of onset of menstrual periods is from 24 to 38 days, based on large databases
and using the 5th to the 95th percentiles.
(A) The top panel demonstrates an individual with a 27-day cycle that is "normal."
(B) The middle panel is a cycle length of 44 days, outside the normal range (infrequent).
(C) The bottom panel depicts a cycle length of 22 days and is, therefore, defined as being "frequent."
Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.
Regularity of menses
Regular and irregular frequency of menses. "Regular" means "cyclically predictable" and
generally reflects the presence of consistently predictable ovulation, typically about 14 days prior
to the onset of menses.
(A) The top panel depicts a 65-day interval where the first cycle length is 29 days and the second
is 31 days, with each menstrual period lasting 5 days and day 2 having the heaviest volume. This
variation of 2 days is well within the definition of regularity: cycle length from first day of one
period to the next is fairly consistent, with each cycle length within 4 days of the others.
(B) The bottom panel demonstrates an irregular cycle, with the first cycle a length of 13 days and
a second cycle of 39 days. This variation in cycle length is outside the normal range for any age
and suggests that the patient is not ovulating regularly or not ovulating at all. Note the
variable duration and flow of the menses, also consistent with some ovulatory disorders, but not
necessary for defining "irregular" onset of menses.
Duration of menses
The panel above demonstrates the two definitions of duration of menses. When a menstrual
period is present and lasts up to 8 days, it is considered "normal." If it is in excess of 8 days,
regardless of volume, as depicted in the center and right cluster, it is deemed "prolonged."
Volume of menses
The volume of a menstrual period comprises the total amount of red cells, serum, transudate, and
tissue discharged from the uterus. The menstrual volume can be quantified with research
laboratory techniques, but for clinical purposes, the patient's perception of volume is of primary
importance. Each of the clusters in the above panel represents a menstrual period. The first
cluster would likely reflect the patient's perception of "normal" volume with a normal period
length of 7 days. The second cluster reflects increased volume, primarily because of prolongation
of the duration of the period: there is no increase in flow rate per day. The third cluster depicts
increased volume, but with a period of normal duration with increase in daily flow rate responsible
for the increased volume. The fourth cluster demonstrates a period with both increased duration
and increased flow rate contributing to the increase in perceived volume.
Intermenstrual bleeding
This depicts an individual with intermenstrual bleeding. She has three periods in this interval
– the first period starts day 1, the next period starts 29 days later, and the next 30 days after
that. The lighter intermenstrual bleeding is depicted as being on day 13 of the first cycle, and
on day 25 of the second. This type of random bleeding is typically seen with a focal lesion or
inflammation, including: cervicitis, cervical or endometrial polyp, or cervical cancer.
Uterine bleeding patterns
Bleeding pattern Definition
Bleeding Any bloody vaginal discharge that requires the use of such
protection as pads or tampons
Spotting Any bloody vaginal discharge that is not large enough to require
sanitary protection
Bleeding/spotting episode One or more consecutive days on which bleeding or spotting

has been entered on the diary card
Bleeding/spotting-free One or more consecutive days on which no bleeding or spotting

interval has been entered on the diary card
Bleeding/spotting segment One bleeding/spotting episode and the immediately following

bleeding/spotting-free interval
Reference period The number of consecutive days upon which the analysis is
based (usually taken as 90 days for women using long-acting
hormonal systems, and 28 or 30 days for women using once-a-
month systems, including combined oral contraception)
Different types of analysis, Number of bleeding/spotting days

which can be undertaken Number of bleeding/spotting episodes
on bleeding patterns within Mean, range of lengths of bleeding/spotting episodes (or
a reference period medians and centiles for box-whisker plot analysis)
Mean, range (medians and centiles) of lengths of
bleeding/spotting-free intervals
Number of spotting days and spotting-only episodes
Data from: Fraser IS. Bleeding arising from the use of exogenous steroids. Baillieres Best Pract Res Clin Obstet Gynaecol
1999; 13:203.
PALM-COEIN classification system for abnormal uterine

bleeding in nongravid reproductive-age women
Basic classification system. The basic system comprises four categories that
are defined by visually objective structural criteria (PALM: polyp,
adenomyosis, leiomyoma, and malignancy and hyperplasia), four that are
unrelated to structural anomalies (COEI: coagulopathy, ovulatory
dysfunction, endometrial, iatrogenic), and one reserved for entities that are
not otherwise classified (N). The leiomyoma category (L) is subdivided into
patients with at least one submucous myoma (LSM) and those with
myomas that do not impact the endometrial cavity (LO). In the 2018
version, the words "submucosal" and "other" do not appear and the phrase
"not yet classified" has been changed to "not otherwise classified."
Reproduced from: Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on
Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine
bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011; 113:3.
Illustration used with the permission of Elsevier Inc. All rights reserved.
Legend updated from: Munro MG, Critchley HO, Fraser IS for the FIGO Menstrual Disorders
Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and
classification of causes of abnormal uterine bleeding in the reproductive years: 2018
revisions. Int J Gynaecol Obstet 2018; 145:393.
Questions to ask to help quantify blood loss during menses
How often do you change your sanitary pad/tampon during peak flow days?
How many pads/tampons do you use over a single menstrual period?
Do you need to change the pad/tampon during the night?
How large are any clots that are passed?
Has a medical provider told you that you are anemic?
Women with a normal volume of menstrual blood loss tend to:
Change pads/tampons at ≥3 hour intervals
Use fewer than 21 pads/tampons per cycle
Seldom need to change the pad/tampon during the night
Have clots less than 1 inch in diameter
Not be anemic
Adapted from: Warner PE, Critchley HD, Lumsden MA, et al. Menorrhagia I: Measured blood loss, clinical features, and
outcome in women with heavy periods: A survey with follow-up data. Am J Obstet Gynecol 2004; 190:1216.
Risk factors for endometrial cancer
Relative risk (RR)
Risk factor
(other statistics are noted when used)
Increasing age 1 to 2% cumulative incidence of endometrial

cancer in females age 50 to 70 years
Unopposed estrogen therapy 2 to 10
Tamoxifen therapy 2
Early menarche NA
Late menopause (after age 55) 2
Nulliparity 2
Polycystic ovary syndrome (chronic 3

anovulation)
Obesity For type I endometrial cancer: OR 1.5 for

overweight (BMI 25.0 to <30 kg/m2 ), 2.5 for
class 1 obesity (30.0 to <35 kg/m2 ), 4.5 for class
2 obesity (35.0 to 39.9 kg/m2 ), and 7.1 for class
3 obesity (≥40.0 kg/m2 ).
For type II: OR 1.2 for overweight (BMI 25.0 to

<30 kg/m2 ), 1.7 for class 1 obesity (30.0 to <35
kg/m2 ), 2.2 for class 2 obesity (35.0 to 39.9
kg/m2 ), and 3.1 for class 3 obesity (≥40.0
kg/m2 ).
Diabetes mellitus 2
Estrogen-secreting tumor NA
Lynch syndrome (hereditary nonpolyposis 13 to 71% lifetime risk

colorectal cancer)
Cowden syndrome 13 to 28% lifetime risk
Family history of endometrial, ovarian, breast, NA

or colon cancer
NA: RR not available; OR: odds ratio; BMI: body mass index.
Data from:
1. Heald B, Mester J, Rybicki L, et al. Frequent gastrointestinal polyps and colorectal adenocarcinomas in a
prospective series of PTEN mutation carriers. Gastroenterology 2010; 139:1927.
2. Pilarski R, Stephens JA, Noss R, et al. Predicting PTEN mutations: an evaluation of Cowden syndrome and
Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet 2011; 48:505.
3. Ramsoekh D, Wagner A, van Leerdam ME, et al. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different
risk profiles may influence clinical management. Hered Cancer Clin Pract 2009; 7:17.
4. Riegert-Johnson DL, Gleeson FC, Roberts M, et al. Cancer and Lhermitte-Duclos disease are common in Cowden
syndrome patients. Hered Cancer Clin Pract 2010; 8:6.
5. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors? J Clin
Oncol 2013; 31:2607.
6. Smith RA, von Eschenbach AC, Wender R, et al. American Cancer Society guidelines for the early detection of
cancer: Update of early detection guidelines for prostate, colorectal, and endometrial cancers. CA Cancer J Clin
2001; 51:38.
7. Tan MH, Mester JL, Ngeow J, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer
Res 2012; 18:400.
8. Ten Broeke SW, van der Klift HM, Tops CMJ, et al. Cancer risks for PMS2-associated Lynch syndrome. J Clin Oncol
2018; 36:2961.
Medications that cause hyperprolactinemia
Frequency of prolactin
Medication class Mechanism
elevation*
Antipsychotics, first generation
Chlorpromazine Moderate Dopamine D2 receptor

blockade within hypothalamic
Fluphenazine High
tuberoinfundibular system.
Haloperidol High
Loxapine Moderate
Perphenazine Moderate
Pimozide Moderate
Thiothixene Moderate
Trifluoperazine Moderate
Antipsychotics, second generation
Aripiprazole None or low Dopamine D2 receptor

blockade.
Asenapine Moderate
Clozapine None or low
Iloperidone None or low
Lurasidone None or low
Olanzapine Low
Paliperidone High
Quetiapine None or low
Risperidone High
Ziprasidone Low
Antidepressants, cyclic
Amitriptyline Low Not well understood. Possibly

by GABA stimulation and
Desipramine Low
indirect modulation of
Clomipramine High prolactin release by serotonin.
Nortriptyline None
Antidepressants, SSRI
Citalopram, fluoxetine, None or low (rare reports) Same as for cyclic

fluvoxamine, paroxetine, antidepressants.
sertraline
Antidepressants, other
Bupropion, venlafaxine, None Not applicable.

mirtazapine, nefazodone,
trazodone
Antiemetic and gastrointestinal
Metoclopramide High Dopamine D2 receptor

blockade.
Domperidone (not available High
in United States)
Prochlorperazine Low
Antihypertensives
Verapamil Low Not well understood. Specific

to verapamil. May involve
calcium influx inhibition within
tuberoinfundibular
dopaminergic neurons.
Methyldopa Moderate Decreased conversion of L-

dopa to dopamine;
suppression of dopamine
synthesis.
Most other None Not applicable.

antihypertensives
(including other calcium
channel blockers)
Opioid analgesics
Methadone, morphine, Transient increase for several Potentially an indirect effect of

others hours following dose mu opiate receptor activation.
Medication-induced hyperprolactinemia can cause decreased libido and erectile dysfunction in

males and galactorrhea and amenorrhea in females.
GABA: gamma-aminobutyric acid; SSRI: selective serotonin reuptake inhibitor.
* Frequency of increase to abnormal prolactin levels with chronic use: high: >50%; moderate: 25
to 50%; low: <25%; none or low: case reports. Effect may be dose dependent.
Data from:
1. Molitch ME. Drugs and prolactin. Pituitary 2008; 11:209.
2. Molitch ME. Medication induced hyperprolactinemia. Mayo Clin Proc 2005; 80:1050.
3. Coker F, Taylor D. Antidepressant-induced hyperprolactinaemia: incidence, mechanisms and management. CNS
Drugs 2010; 24:563.
4. Drugs for psychiatric disorders. Treat Guidel Med Lett 2013; 11:53.
Screening for bleeding disorders in women with heavy menstrual

bleeding
Initial screening for an underlying disorder of hemostasis in patients with

excessive menstrual bleeding should be structured by medical history (positive
screen comprises any of the following):*
Heavy menstrual bleeding since menarche
One of the following:
Postpartum hemorrhage
Surgery-related bleeding
Bleeding associated with dental work
Two or more of the following symptoms:
Bruising one to two times per month
Epistaxis one to two times per month
Frequent gum bleeding
Family history of bleeding symptoms
* Patients with a positive screen should be considered for further evaluation, including
consultation with a hematologist and testing of von Willebrand factor and ristocetin cofactor.
Original figure modified for this publication. Kouides PA, Conard J, Peyvandi F, et al. Hemostasis and menstruation:
appropriate investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil
Steril 2005; 84:1345. Table used with the permission of Elsevier Inc. All rights reserved.
Evaluation and differential diagnosis of abnormal uterine bleeding (AUB)

in nonpregnant reproductive-age women
Other Differential diagnosis

Bleeding associated
Evaluation
pattern clinical Common Less common
features etiologies etiologies
Regular menses Enlarged uterus Uterine leiomyoma - Pelvic

that are heavy on examination, ultrasound
or prolonged discrete masses
- Saline infusion
may be noted
sonography or
hysteroscopy (if
intracavitary
pathology is
suspected)
- Dysmenorrhea Adenomyosis Pelvic

ultrasound
- Enlarged,
boggy uterus on
examination
- Family history Bleeding disorder Testing for

of bleeding bleeding
disorder disorder
- Symptoms of
bleeding
diathesis
- Anticoagulant
therapy
Risk factors for Endometrial Endometrial

uterine carcinoma or sampling
malignancy uterine sarcoma
Regular menses Endometrial polyp - Pelvic

with ultrasound
intermenstrual
- Saline infusion
bleeding
sonography or
hysteroscopy (if
available)

Recent history of Chronic Endometrial

uterine or endometritis sampling
cervical
procedure or
childbirth,
particularly if
infection was
present
Irregular Ovulatory
bleeding, may dysfunction:
be more or less
Hirsutism, acne, PCOS Total
frequent than
and/or obesity testosterone
normal menses
and/or other
and volume and
androgens (may
duration may
not be increased
vary
in all women
with PCOS)
Galactorrhea Hyperprolactinemia Prolactin
- Recent weight Thyroid disease Thyroid function

gain or loss tests
- Heat or cold
intolerance
- Family history
of thyroid
dysfunction

Secondary History of Ovulatory Refer to

amenorrhea irregular dysfunction ovulatory
bleeding dysfunction
above
Poor nutrition or Hypothalamic - Follicle-

intense exercise amenorrhea stimulating
hormone
- Luteinizing
hormone
- Estradiol
Hot flushes Premature ovarian Follicle-

insufficiency stimulating
hormone
Recent history of Cervical stenosis On pelvic

uterine or examination,
cervical instrument
procedure or cannot be
childbirth, passed through
particularly if
infection was internal cervical

present (menses os
may present,
Intrauterine Hysteroscopy
but abnormally
adhesions
light or brief)
(Asherman
syndrome)
Irregular or Iatrogenic AUB

heavy bleeding
in a
patient using
hormonal
contraceptives
or with an
intrauterine
device
Other uncommon etiologies of AUB include a uterine arteriovenous malformation or

endometriosis.
PCOS: polycystic ovarian syndrome.
Causes of heavy or prolonged menses
Coagulopathy Structural lesion

von Willebrand disease Uterine leiomyomas (fibroids)
Thrombocytopenia (due to idiopathic Adenomyosis

thrombocytopenic purpura, hypersplenism,
Endometrial polyps
chronic renal failure)
Other
Acute leukemia
Anticoagulants Endometritis
Advanced liver disease Hypothyroidism
Intrauterine device
Neoplasm
Hyperestrogenism
Endometrial hyperplasia or carcinoma
Endometriosis
Uterine sarcoma
Patients who should undergo evaluation for endometrial hyperplasia or

endometrial cancer
Abnormal uterine bleeding
Postmenopausal patients – Any uterine bleeding, regardless of volume (including spotting

or staining). Pelvic ultrasound to evaluate endometrial thickness is an alternative to
endometrial sampling in appropriately selected patients. A thickened endometrium should
be further evaluated with endometrial sampling.
Age 45 years to menopause – In any patient, bleeding that is frequent (interval between the
onset of bleeding episodes is <21 days), heavy, or prolonged (>8 days). In patients who are
ovulatory, this includes intermenstrual bleeding.
Younger than 45 years – Any abnormal uterine bleeding in patients with BMI ≥30 kg/m2 . In
patients with BMI <30 kg/m2 , abnormal uterine bleeding that is persistent and occurs in the
setting of one of the following: chronic ovulatory dysfunction, other exposure to estrogen
unopposed by progesterone, failed medical management of the bleeding, or patients at
high risk of endometrial cancer (eg, Lynch syndrome, Cowden syndrome).
In addition, endometrial neoplasia should be suspected in premenopausal patients who are

anovulatory and have prolonged periods of amenorrhea (six or more months).
Cervical cytology results
Presence of AGC-endometrial.
Presence of AGC-all subcategories other than endometrial – If ≥35 years of age or at risk
for endometrial cancer (risk factors or symptoms).
Presence of benign-appearing endometrial cells in patients ≥40 years of age who also have
abnormal uterine bleeding or risk factors for endometrial cancer.
Other indications
Monitoring of patients with endometrial pathology (eg, endometrial hyperplasia).
Screening in patients at high risk of endometrial cancer (eg, Lynch syndrome).
These recommendations are based on an average age of menopause of 51 years. Evaluation of

patients who undergo menopause earlier should be individualized based on gynecologic history
and risk of endometrial neoplasia.
BMI: body mass index; AGC: atypical glandular cells.
Causes of intermenstrual bleeding
Drugs
Oral contraceptives
Infection
Cervicitis*
Endometritis
Sexually transmitted ulcerations*
Vaginitis
Benign growths
Cervical polyps*
Endometrial polyps
Ectropion*
Uterine fibroids
Vulvar skin tags, sebaceous cysts, condylomata
Vaginal Gartner's duct cysts, polyps, adenosis
Cancer
Uterine
Cervical*
Vaginal
Vulvar
Rarely ovarian or fallopian tube
Trauma
Previous cesarean delivery (ie, cesarean scar defect)
* Often cause postcoital bleeding.
Causes of ovulatory dysfunction
Primary hypothalamic-pituitary dysfunction

Immaturity at onset of menarche or perimenopausal decline
Intense exercise
Eating disorders
Stress
Idiopathic hypogonadotropic hypogonadism
Hyperprolactinemia
Lactational amenorrhea
Pituitary adenoma or other pituitary tumors
Kallman syndrome
Tumors, trauma, or radiation of the hypothalamic or pituitary area
Sheehan's syndrome
Empty sella syndrome
Lymphocytic hypophysitis (autoimmune diseases)
Other disorders
Polycystic ovary syndrome
Hyperthyroidism or hypothyroidism
Hormone-producing tumors (adrenal, ovarian)
Chronic liver or renal disease
Cushing's disease
Congenital adrenal hyperplasia
Premature ovarian failure, which may be autoimmune, genetic, surgical idiopathic, or related
to drugs or radiation
Turner syndrome
Androgen insensitivity syndrome
Medications
Estrogen-progestin contraceptives
Progestins
Antidepressant and antipsychotic drugs
Corticosteroids
Chemotherapeutic agents
Sonohysterogram of endometrial polyp
Sonohysterograms of two patients, both with an endometrial polyp; Doppler shows flow to the polyp via
Courtesy of Andrew M Kaunitz, MD.
Saline infusion sonohysterogram of a submucous

myoma
A posterior mid-segment submucous myoma measuring 1.6 x 1.9

cm is identified after infusion of saline. The distance from the back
of the myoma to the serosal surface measures 1.2 cm (calipers). The
endometrium surrounding the fluid is thin, compatible with early
proliferative phase.
Courtesy of Steven Goldstein, MD.
Fibroid locations in the uterus
These figures depict the various types and locations of fibroids. An individual may have one or
more types of fibroids.
PALM-COEIN subclassification system for leiomyomas
FIGO leiomyoma subclassification system. System 2 classification system including the FIGO leiomyoma
subclassification system. The system that includes the tertiary classification of leiomyomas categorizes t
submucous group according to the original Wamsteker et al system[1] and adds categorizations for intra
subserosal, and transmural lesions. Intracavitary lesions are attached to the endometrium by a narrow s
(≤10% or the mean of three diameters of the leiomyoma) and are classified as Type 0, whereas Types 1 a
require a portion of the lesion to be intramural: with Type 1 being less than 50% of the mean diameter a
at least 50%. Type 3 lesions are totally intramural but also about the endometrium. Type 3 are formally
distinguished from Type 2 with hysteroscopy using the lowest possible intrauterine pressure necessary t
visualization. Type 4 lesions are intramural leiomyomas that are entirely within the myometrium, with no
extension to the endometrial surface or to the serosa. Subserous (Types 5, 6, and 7) leiomyomas represe
mirror image of the submucous leiomyomas: with Type 5 being at least 50% intramural, Type 6 being les
50% intramural, and Type 7 being attached to the serosa by a stalk that is also ≤10% or the mean of thre
diameters of the leiomyoma. Classification of lesions that are transmural are categorized by their relatio
both the endometrial and the serosal surfaces. The endometrial relationship is noted first, with the seros
relationship second (eg, Type 2-5). An additional category, Type 8, is reserved for leiomyomas that do no
to the myometrium at all, and would include cervical lesions (demonstrated), those that exist in the roun
broad ligaments without direct attachment to the uterus, and other so-called "parasitic" lesions.
FIGO: International Federation of Gynecology and Obstetrics.
Reference:
1. Wamsteker K, Emanuel MH, de Kruif JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine
Results regarding the degree of intramural extension. Obstet Gynecol 1993; 82:736.

From: Munro MG. Abnormal Uterine Bleeding. Cambridge: Cambridge University Press, 2010. Copyright © 2010 M. Munro. Repri
the permission of Cambridge University Press.
Updated with information from: Munro MG, Critchley HOD, Fraser IS, FIGO Menstrual Disorders Committee. The two FIGO system
normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive y
revisions. In J Gynaecol Obstet 2018; 143:393.
Saline infusion sonography of a patient with

uterine bleeding
Saline infusion sonography of a patient with uterine bleeding

reveals fluffy endometrial tissue occupying the right lateral half of
the endometrial cavity while the left side is thin.
Courtesy of Steven Goldstein, MD.
Contributor Disclosures
Andrew M Kaunitz, MD Grant/Research/Clinical Trial Support: AbbVie [Polycystic ovary
syndrome];Bayer[Treatment of menopausal symptoms];Exeltis[Oral contraception];Medicines360
[Heavy menstrual bleeding];Merck [Contraceptive implant];Mithra[Treatment of menopausal
symptoms].
All of the relevant financial relationships listed have been mitigated. Robert L Barbieri,
MD No relevant financial relationship(s) with ineligible companies to disclose. Deborah Levine, MD No
relevant financial relationship(s) with ineligible companies to disclose. Alana Chakrabarti, MD No
relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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Abnormal uterine bleeding in nonpregnant

● Terminology of normal menstrual bleeding (see "Normal menstrual cycle", section on

● Bleeding in adolescents (see "Abnormal uterine bleeding in adolescents: Evaluation and

● Bleeding in perimenopausal patients (see "Clinical manifestations and diagnosis of

● Bleeding in postmenopausal patients (see "Approach to the patient with

● Abnormalities in frequency ( figure 1)

• Infrequent – Infrequent menstrual bleeding refers to periods that start at intervals

• Absent – Absence of menses is either primary (absence of menarche by age 15

● Irregular bleeding ( figure 2) – The definition of irregular bleeding depends on

• 18 to 25 years: cycle length variance >9 days

● Prolonged menstrual bleeding ( figure 3) is defined as menstrual bleeding

● Abnormalities in volume ( figure 4)

• Light – Light menstrual bleeding is uncommon and rarely related to pathology,

● Intermenstrual bleeding ( figure 5) refers to AUB that occurs between well-defined

Intermenstrual bleeding can be cyclical or acyclical.

• Cyclical midcycle intermenstrual bleeding – A small amount of bleeding arising

• Acyclical intermenstrual bleeding – Intermenstrual bleeding that is not cyclical or

bleeding can be indicative of pathologic process, such as cervical or endometrial

The International Federation of Gynecology and Obstetrics (FIGO) classification system

INITIAL EVALUATION OF ALL PATIENTS

Assess hemodynamic stability — Initial triage includes assessment of hemodynamic

Gynecologic and obstetric history

• Does bleeding occur between menstrual periods?

• Is the bleeding associated with dysmenorrhea or dyspareunia (ie, suggestive of

• Is the patient certain that the bleeding is from the vagina?

fibroid uterus or a neoplasm. Evaluation of hematuria and rectal bleeding is

• Were there precipitating factors, such as trauma, intercourse, or a procedure?

● History of obstetric or gynecologic surgery – A history of obstetric or gynecologic

- A prior cesarean birth can result in a cesarean scar defect (particularly if a

- Past myomectomy suggests the possibility of recurrent or persistent uterine

- Past excisional cervical procedures performed for diagnosis or management of

- Rarely, uterine surgery can result in an arteriovenous malformation (also

● Bleeding disorders – Bleeding disorders may present at menarche or later during a

● Endocrine disorders – Thyroid disease is often associated with oligomenorrhea or

Hyperprolactinemia is also associated with amenorrhea. (See 'Heavy menstrual

Physical examination — The goal of the physical examination is to look for signs of

A complete pelvic examination should be performed, with a particular focus on:

● Presence of an adnexal mass or tenderness – This may reflect a tubo-ovarian abscess

Pregnancy test — Pregnancy should be excluded in all reproductive-age patients with AUB.

Diagnosis of pregnancy is discussed in detail separately. (See "Clinical manifestations and

Based on bleeding pattern

Heavy menstrual bleeding — Based on current terminology, heavy menstrual bleeding

[41]. (See 'Definitions' above.)

• Uterine fibroids (an enlarged uterus or discrete mass may be palpated on

• Adenomyosis (a boggy uterus may be palpated on examination or the patient may

• Endometrial polyps (in the absence of a prolapsed polyp, physical examination is

• Uterine arteriovenous malformation (also referred to as congenital or acquired

• Thyroid disease – A serum thyroid-stimulating hormone (TSH) level should be

Intermenstrual bleeding — Intermenstrual uterine bleeding may be related to a variety of

• Endometrial polyps (in the absence of a prolapsed polyp, physical examination is

postmenstrual bleeding [46]. The mechanism by which this occurs is discussed in

● Endometrial sampling is typically performed for patients with intermenstrual bleeding

Endometrial sampling may also be performed in patients with intermenstrual bleeding

Irregular bleeding — Irregular uterine bleeding is most commonly associated with

While further evaluation is not generally required to confirm ovulatory dysfunction, it is

• Prolactin level – A prolactin level should be measured in patients who complain of

• Androgen levels – Serum androgens should be measured in patients with irregular

suspected and the patient should be evaluated for an androgen-secreting tumor of

• Follicle-stimulating hormone (FSH) or luteinizing hormone (LH) – FSH and LH are

• Estrogen levels – As with FSH, if premature ovarian insufficiency is suspected, a

Amenorrhea — Amenorrhea refers to absence of bleeding for at least three usual cycle