Version May 2024
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")
●Bleeding in postmenopausal patients (see "Approach to the patient with postmenopausal uterine bleeding")
●Bleeding in pregnant patients (see "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation")
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
•26 to 41 years: cycle length variance >7 days
•42 to 45 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." Patient self-reports, however, can be inaccurate indicators of the quantity of blood loss [4-9]. 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) [10].
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 [9,11,12]. 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 [13,14].
•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 [15].
For research purposes, <5 mL is considered "low volume," a metric that can only be assessed quantitatively with methods like the alkaline hematin assay [11,16].
●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 [17]. This is thought to be associated with the midcycle drop in circulating estradiol levels that occurs just after ovulation [18].
•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 [19-21]. 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 [22]. However, in young healthy patients, vital signs, including postural changes, may be normal early in the course of significant bleeding due to compensatory mechanisms [23].
History
Gynecologic and obstetric history
●Recent or current pregnancy – Pregnancy history is obtained; bleeding is common in pregnancy (all trimesters) and after pregnancy loss or termination. (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)
●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).
•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 (AVM); enhanced myometrial vascularity (EMV) is a distinct entity and occurs in the setting of pregnancy and retained products of conception.
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.)
For patients using anticoagulants, the incidence of AUB differs based on the anticoagulant drug class. In a retrospective study including 645 patients with AUB after initiating therapeutic anticoagulation, those taking single-agent direct oral anticoagulants (DOACs; eg, apixaban, dabigatran, rivaroxaban, edoxaban) compared with a vitamin K antagonist (eg, warfarin) were less likely to have AUB (adjusted odds ratio [aOR] 0.70, 95% CI 0.51-0.97) [25]. AUB rates also trended lower in the low molecular weight heparin (LMWH; eg, enoxaparin, dalteparin) group, but this was not statistically significant (aOR 0.72, 95% CI 0.51-1.02).
●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 [26]. 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) [26-32]. (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 [33,34]. (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 may develop AUB. For example, patients with type 1 diabetes mellitus, celiac disease, chronic kidney disease, or opioid use disorder 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 [35-40]. Similarly, patients with connective tissue disorders (eg, Ehlers-Danlos syndrome) may develop HMB [41]. (See 'Amenorrhea' below and "Epidemiology and causes of secondary amenorrhea", section on 'Systemic illness' and "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Clinical manifestations'.)
Patients with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or coronavirus disease 2019 (COVID-19) vaccination may also report transient changes in their menstrual cycle [42-45].
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) [46-48].
●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 "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation" 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 [49]. (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 (AVM; a rare cause of HMB that should be suspected when an invasive procedure [eg, dilation and curettage in a nonpregnant patient] for unexplained bleeding aggravates the bleeding). AVM represents a distinct entity from enhanced myometrial vascularity (EMV), which is associated with retained products of conception and occurs postpartum or after pregnancy loss/termination [50,51]. (See "Causes of female genital tract bleeding", section on 'Not otherwise classified (AUB-N)'.)
●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 [32]. 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'.)
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 (also known as an isthmocele or niche), and approximately one-third of patients with this condition experience cyclical, postmenstrual bleeding (also termed cesarean scar disorder) [52,53]. This is discussed in detail separately. (See "Causes of female genital tract bleeding", section on 'Not otherwise classified (AUB-N)' and "Cesarean birth: Postoperative care, complications, and long-term sequelae", section on 'Scar complications'.)
●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) [54]. 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 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 [55]) and occurs in the setting of one of the following: a history of unopposed estrogen exposure (eg, obesity, chronic ovulatory dysfunction) [56,57], 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 [58-61]. This age threshold is also consistent with American College of Obstetricians and Gynecologists (ACOG) guidelines [56,62]. (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 [63]. (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 [64]. 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 [65]. 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 [66]. (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 [67,68]. (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 [69], while ultrasound alone has limited sensitivity and specificity for the characterization of these lesions [70,71]. 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 [70,72]. SIS also is able to identify asymmetric or focal endometrial thickening, a potentially important marker of endometrial neoplasia (image 3) [69].
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 [73].
●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)")
PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: von Willebrand disease".)
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.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
