ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis

Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis
Literature review current through: May 2024.
This topic last updated: May 03, 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 cramping or pain during sexual relations with deep penetration (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 in adults and adolescents" 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, weight loss, eating disorder).

Medications that can cause AUB include anticoagulants, which may result in heavy or prolonged uterine bleeding, medications that cause hyperprolactinemia, which can result in oligomenorrhea or amenorrhea (table 6), and other medications (eg, tamoxifen, chemotherapy, corticosteroids) (table 1). (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 often 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 [42-46].

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, distal 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) [47-49].

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 — Many patients will ultimately need an ultrasound as part of their evaluation. This may be done as part of the initial evaluation or during the secondary evaluation. The timing of ultrasound evaluation is often based on the patient's bleeding pattern and the clinician's concern for a structural cause (eg, uterine fibroid, endometrial polyp) of bleeding. (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 [50]. (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 all patients with a TCu-380A 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 dysmenorrhea or chronic pelvic pain). (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 [51,52]. (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 "Office-based 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 spotting or bleeding (also termed cesarean scar disorder) [53,54]. 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 'Uterine and abdominal 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 with 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) [55]. 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 [56]) and occurs in the setting of one of the following: a history of unopposed estrogen exposure (eg, obesity, chronic ovulatory dysfunction) [57,58], 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 [59-62]. This age threshold is also consistent with American College of Obstetricians and Gynecologists (ACOG) guidelines [57,63]. (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 by 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 [64]. (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, oral progestins, 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 "Office-based 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 because they have not engaged in penetrative sexual intercourse). 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 [65]. 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 [66]. 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 [67]. (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 [68,69]. (See "Hysteroscopy: Instruments and procedure".)

We suggest SIS for most patients for intracavitary evaluation. Both SIS and hysteroscopy are effective tests for diagnosing endometrial polyps and submucosal leiomyoma [70], while ultrasound alone has limited sensitivity and specificity for the characterization of these lesions [71,72]. 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 [71,73]. SIS also is able to identify asymmetric or focal endometrial thickening, a potentially important marker of endometrial neoplasia (image 3) [70].

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 [74].

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 periods (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.

  1. Munro MG, Critchley HOD, Fraser IS, 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; 143:393.
  2. NICE Guideline. Heavy menstrual bleeding (NG44). https://www.rcog.org.uk/en/guidelines-research-services/guidelines/heavy-menstrual-bleeding-nice-clinical-guideline-44/.
  3. Practice Bulletin No. 168 Summary: Cervical Cancer Screening and Prevention. Obstet Gynecol 2016; 128:923.
  4. Greenberg M. The meaning of menorrhagia: an investigation into the association between the complaint of menorrhagia and depression. J Psychosom Res 1983; 27:209.
  5. Hurskainen R, Aalto AM, Teperi J, et al. Psychosocial and other characteristics of women complaining of menorrhagia, with and without actual increased menstrual blood loss. BJOG 2001; 108:281.
  6. Wright B, Gannon MJ, Greenberg M, et al. Psychiatric morbidity following endometrial ablation and its association with genuine menorrhagia. BJOG 2003; 110:358.
  7. Grant C, Gallier L, Fahey T, et al. Management of menorrhagia in primary care-impact on referral and hysterectomy: data from the Somerset Morbidity Project. J Epidemiol Community Health 2000; 54:709.
  8. Clarke A, Black N, Rowe P, et al. Indications for and outcome of total abdominal hysterectomy for benign disease: a prospective cohort study. Br J Obstet Gynaecol 1995; 102:611.
  9. Hallberg L, Högdahl AM, Nilsson L, Rybo G. Menstrual blood loss--a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand 1966; 45:320.
  10. Warner PE, Critchley HO, 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.
  11. HALLBERG L, NILSSON L. DETERMINATION OF MENSTRUAL BLOOD LOSS. Scand J Clin Lab Invest 1964; 16:244.
  12. Cole SK, Thomson AM, Billewicz WZ, Black AE. Haematological characteristics and menstrual blood losses. J Obstet Gynaecol Br Commonw 1972; 79:994.
  13. Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97:734.
  14. Magnay JL, Nevatte TM, Dhingra V, O'Brien S. Menstrual blood loss measurement: validation of the alkaline hematin technique for feminine hygiene products containing superabsorbent polymers. Fertil Steril 2010; 94:2742.
  15. Haththotuwa R, Goonewardene M, Desai S, et al. Management of abnormal uterine bleeding in low- and high-resource settings: consideration of cultural issues. Semin Reprod Med 2011; 29:446.
  16. Newton JR, Barnard G, Collins W. A rapid method for measuring blood loss using automatic extraction. Contraception 1977; 16:269.
  17. Papanicolaou GN. Sexual cycle in the human female. Am J Anat 1933; 52:519.
  18. Hilgers TW, Daly KD, Prebil AM, Hilgers SK. Natural family planning III. Intermenstrual symptoms and estimated time of ovulation. Obstet Gynecol 1981; 58:152.
  19. Fraser IS, Critchley HO, Munro MG, et al. A process designed to lead to international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril 2007; 87:466.
  20. 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.
  21. Woolcock JG, Critchley HO, Munro MG, et al. Review of the confusion in current and historical terminology and definitions for disturbances of menstrual bleeding. Fertil Steril 2008; 90:2269.
  22. Pacagnella RC, Souza JP, Durocher J, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS One 2013; 8:e57594.
  23. Parks JK, Elliott AC, Gentilello LM, Shafi S. Systemic hypotension is a late marker of shock after trauma: a validation study of Advanced Trauma Life Support principles in a large national sample. Am J Surg 2006; 192:727.
  24. Peipert JF, Boardman LA, Sung CJ. Performance of clinical and laparoscopic criteria for the diagnosis of upper genital tract infection. Infect Dis Obstet Gynecol 1997; 5:291.
  25. Brioso XB, Bolt M, Sammel MD, McKenney K. Abnormal uterine bleeding in anticoagulated patients by drug class: outcomes and management. Am J Obstet Gynecol 2023; 229:318.e1.
  26. Committee on Adolescent Health Care, Committee on Gynecologic Practice. Committee Opinion No.580: von Willebrand disease in women. Obstet Gynecol 2013; 122:1368. Reaffirmed 2020.
  27. Kadir RA, Economides DL, Sabin CA, et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet 1998; 351:485.
  28. Kouides PA, Byams VR, Philipp CS, et al. Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid. Br J Haematol 2009; 145:212.
  29. Dilley A, Drews C, Miller C, et al. von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia. Obstet Gynecol 2001; 97:630.
  30. Philipp CS, Faiz A, Dowling N, et al. Age and the prevalence of bleeding disorders in women with menorrhagia. Obstet Gynecol 2005; 105:61.
  31. Lukes AS, Kadir RA, Peyvandi F, Kouides PA. Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact. Fertil Steril 2005; 84:1338.
  32. Nebgen DR, Rhodes HE, Hartman C, et al. Abnormal Uterine Bleeding as the Presenting Symptom of Hematologic Cancer. Obstet Gynecol 2016; 128:357.
  33. Kakuno Y, Amino N, Kanoh M, et al. Menstrual disturbances in various thyroid diseases. Endocr J 2010; 57:1017.
  34. Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf) 1999; 50:655.
  35. Lim VS, Henriquez C, Sievertsen G, Frohman LA. Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation. Ann Intern Med 1980; 93:21.
  36. Gómez F, de la Cueva R, Wauters JP, Lemarchand-Béraud T. Endocrine abnormalities in patients undergoing long-term hemodialysis. The role of prolactin. Am J Med 1980; 68:522.
  37. Sievertsen GD, Lim VS, Nakawatase C, Frohman LA. Metabolic clearance and secretion rates of human prolactin in normal subjects and in patients with chronic renal failure. J Clin Endocrinol Metab 1980; 50:846.
  38. Hochstetler LA, Flanigan MJ, Lim VS. Abnormal endocrine tests in a hemodialysis patient. J Am Soc Nephrol 1994; 4:1754.
  39. Lania A, Gianotti L, Gagliardi I, et al. Functional hypothalamic and drug-induced amenorrhea: an overview. J Endocrinol Invest 2019; 42:1001.
  40. Gudin JA, Laitman A, Nalamachu S. Opioid Related Endocrinopathy. Pain Med 2015; 16 Suppl 1:S9.
  41. Kumskova M, Flora GD, Staber J, et al. Characterization of bleeding symptoms in Ehlers-Danlos syndrome. J Thromb Haemost 2023; 21:1824.
  42. Wang S, Mortazavi J, Hart JE, et al. A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics. Am J Obstet Gynecol 2022; 227:739.e1.
  43. Tayyaba Rehan S, Imran L, Mansoor H, et al. Effects of SARS-CoV-2 infection and COVID-19 pandemic on menstrual health of women: A systematic review. Health Sci Rep 2022; 5:e881.
  44. Anto-Ocrah M, Valachovic T, Chen M, et al. Coronavirus Disease 2019 (COVID-19)-Related Stress and Menstrual Changes. Obstet Gynecol 2023; 141:176.
  45. Alvergne A, Boniface E, Darney B, et al. Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination. Obstet Gynecol 2024; 143:83.
  46. Edelman A, Boniface ER, Male V, et al. Timing of Coronavirus Disease 2019 (COVID-19) Vaccination and Effects on Menstrual Cycle Changes. Obstet Gynecol 2024; 143:585.
  47. O'Connor RE, Bibro CM, Pegg PJ, Bouzoukis JK. The comparative sensitivity and specificity of serum and urine HCG determinations in the ED. Am J Emerg Med 1993; 11:434.
  48. Norman RJ, Menabawey M, Lowings C, et al. Relationship between blood and urine concentrations of intact human chorionic gonadotropin and its free subunits in early pregnancy. Obstet Gynecol 1987; 69:590.
  49. Johnson SR, Miro F, Barrett S, Ellis JE. Levels of urinary human chorionic gonadotrophin (hCG) following conception and variability of menstrual cycle length in a cohort of women attempting to conceive. Curr Med Res Opin 2009; 25:741.
  50. Munro MG, Critchley HO, Broder MS, et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011; 113:3.
  51. Groszmann YS, Healy Murphy AL, Benacerraf BR. Diagnosis and management of patients with enhanced myometrial vascularity associated with retained products of conception. Ultrasound Obstet Gynecol 2018; 52:396.
  52. Agarwal N, Chopra S, Aggarwal N, Gorsi U. Congenital Uterine Arteriovenous Malformation Presenting as Postcoital bleeding: A Rare Presentation of a Rare Clinical Condition. J Clin Imaging Sci 2017; 7:11.
  53. van der Voet LF, Bij de Vaate AM, Veersema S, et al. Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding. BJOG 2014; 121:236.
  54. Klein Meuleman SJM, Murji A, van den Bosch T, et al. Definition and Criteria for Diagnosing Cesarean Scar Disorder. JAMA Netw Open 2023; 6:e235321.
  55. Fritz MA, Speroff L. Hirsutism. In: Clinical Gynecologic Endocrinology and Infertility, 8th ed., Lippincott Williams & Wilkins, Philadelphia 2011. p.533.
  56. Lethaby A, Suckling J, Barlow D, et al. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004; :CD000402.
  57. Committee on Practice Bulletins—Gynecology. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol 2013; 122:176. Reaffirmed 2022.
  58. Brown AJ, Westin SN, Broaddus RR, Schmeler K. Progestin intrauterine device in an adolescent with grade 2 endometrial cancer. Obstet Gynecol 2012; 119:423.
  59. http://seer.cancer.gov/statfacts/html/corp.html (Accessed on September 11, 2013).
  60. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Uterine cancer. http://seer.cancer.gov/statfacts/html/corp.html (Accessed on September 12, 2021).
  61. Reed SD, Newton KM, Clinton WL, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol 2009; 200:678.e1.
  62. http://seer.cancer.gov/statfacts/html/corp.html (Accessed on June 06, 2016).
  63. Committee on Practice Bulletins—Gynecology. Practice bulletin no. 128: Diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 2012; 120:197. Reaffirmed 2021.
  64. Wise MR, Gill P, Lensen S, et al. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol 2016; 215:598.e1.
  65. Timor-Tritsch IE, Haynes MC, Monteagudo A, et al. Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations. Am J Obstet Gynecol 2016; 214:731.e1.
  66. Khan F, Jamaat S, Al-Jaroudi D. Saline infusion sonohysterography versus hysteroscopy for uterine cavity evaluation. Ann Saudi Med 2011; 31:387.
  67. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications. J Minim Invasive Gynecol 2013; 20:562.
  68. APGO educational series on women's health issues. Clinical management of abnormal uterine bleeding. Association of Professors of Gynecology and Obstetrics, 2006.
  69. Bradley LD. Diagnosis of abnormal uterine bleeding with biopsy or hysteroscopy. Menopause 2011; 18:425.
  70. La Sala GB, Blasi I, Gallinelli A, et al. Diagnostic accuracy of sonohysterography and transvaginal sonography as compared with hysteroscopy and endometrial biopsy: a prospective study. Minerva Ginecol 2011; 63:421.
  71. Kelekci S, Kaya E, Alan M, et al. Comparison of transvaginal sonography, saline infusion sonography, and office hysteroscopy in reproductive-aged women with or without abnormal uterine bleeding. Fertil Steril 2005; 84:682.
  72. Farquhar C, Ekeroma A, Furness S, Arroll B. A systematic review of transvaginal ultrasonography, sonohysterography and hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women. Acta Obstet Gynecol Scand 2003; 82:493.
  73. Van den Bosch T, Verguts J, Daemen A, et al. Pain experienced during transvaginal ultrasound, saline contrast sonohysterography, hysteroscopy and office sampling: a comparative study. Ultrasound Obstet Gynecol 2008; 31:346.
  74. https://www.nice.org.uk/guidance/ng88/chapter/Recommendations#history-physical-examination-and-laboratory-tests (Accessed on October 29, 2018).
Topic 3263 Version 63.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟