Abnormal Uterine Bleeding in Premenopausal Women

 

Am Fam Physician. 2019 Apr 1;99(7):435-443.

  Patient information: A handout on this topic is available at https://familydoctor.org/condition/abnormal-uterine-bleeding/.

Author disclosure: No relevant financial affiliations.

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

Abnormal uterine bleeding is a common condition, with a prevalence of 10% to 30% among women of reproductive age.1 It negatively affects quality of life and is associated with financial loss, decreased productivity, poor health, and increased use of health care resources.24 In 2011 the International Federation of Gynecology and Obstetrics convened a working group that produced standardized definitions and classifications for menstrual disorders, which the American College of Obstetricians and Gynecologists subsequently endorsed.5,6 The updated terminology pertains only to nonpregnant women of reproductive age, which is the scope of this review.

WHAT IS NEW ON THIS TOPIC

The acronym PALM-COEIN facilitates the classification of abnormal uterine bleeding, with PALM referring to structural etiologies (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia), and COEIN referring to nonstructural etiologies (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified).

Among medical therapies, the 20-mcg-per-day formulation of the levonorgestrel-releasing intrauterine system (Mirena) is most effective for decreasing heavy menstrual bleeding (71% to 95% reduction in blood loss) and performs similarly to hysterectomy when quality-adjusted life years are considered.

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

The International Federation of Gynecology and Obstetrics classification system should be used to characterize abnormal uterine bleeding.

C

5, 6

All patients with abnormal uterine bleeding should be tested for pregnancy and anemia.

C

6

Endometrial biopsy should be performed in all patients with abnormal uterine bleeding who are 45 years or older, in younger patients with a significant history of unopposed estrogen exposure, persistent bleeding, or in whom medical management is ineffective.

C

6

Transvaginal ultrasonography is the first-line imaging choice for evaluating abnormal uterine bleeding in most patients.

C

6, 36

The 20-mcg-per-day formulation of the levonorgestrel-releasing intrauterine system (Mirena) is more effective than other medical therapies for reducing heavy menstrual bleeding.

A

44, 47

Hysterectomy is the most effective treatment for reducing heavy menstrual bleeding.

A

44, 47


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

The International Federation of Gynecology and Obstetrics classification system should be used to characterize abnormal uterine bleeding.

C

5, 6

All patients with abnormal uterine bleeding should be tested for pregnancy and anemia.

C

6

Endometrial biopsy should be performed in all patients with abnormal uterine bleeding who are 45 years or older, in younger patients with a significant history of unopposed estrogen exposure, persistent bleeding, or in whom medical management is ineffective.

C

6

Transvaginal ultrasonography is the first-line imaging choice for evaluating abnormal uterine bleeding in most patients.

C

6, 36

The 20-mcg-per-day formulation of the levonorgestrel-releasing intrauterine system (Mirena) is more effective than other medical therapies for reducing heavy menstrual bleeding.

A

44, 47

Hysterectomy is the most effective treatment for reducing heavy menstrual bleeding.

A

44, 47


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

Definitions

Abnormal uterine bleeding is a symptom, not a diagnosis; the term is used to describe bleeding that falls outside population-based 5th to 95th percentiles for menstrual regularity, frequency, duration, and volume (Table 1).7 Abnormal bleeding is considered chronic when it has occurred for most of the previous six months, or acute when an episode of heavy bleeding warrants immediate intervention.5 Intermenstrual bleeding is bleeding that occurs between otherwise normal menstrual periods.7 Use of imprecise terms such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding is now discouraged.

 Enlarge     Print

TABLE 1

Definitions of Normal and Abnormal Menstrual Bleeding

Menstrual cycle termsDescriptive termsDefinition

Frequency (interval between the start of each menstrual cycle)

Infrequent

> 38 days

Normal

24 to 38 days

Frequent

< 24 days

Regularity (variation of menstrual cycle length, measured over 12 months)

Regular

± 2 to 20 days over 12 months

Irregular

> 20 days over 12 months

Duration of menstruation

Shortened

< 4.5 days

Normal

4.5 to 8 days

Prolonged

> 8 days

Volume (total blood loss each menstrual cycle)

Light

< 5 mL

Normal

5 to 80 mL

Heavy

> 80 mL

Other terms

Amenorrhea

No bleeding for 90 days

Primary amenorrhea

Absent menarche by 15 years of age

Secondary amenorrhea

Amenorrhea for 6 months with previously regular menstrual cycles

Menopause

Amenorrhea for 12 months without other apparent cause

Precocious menstruation

Menarche before 9 years of age


Adapted with permission from Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):389.

TABLE 1

Definitions of Normal and Abnormal Menstrual Bleeding

Menstrual cycle termsDescriptive termsDefinition

Frequency (interval between the start of each menstrual cycle)

Infrequent

> 38 days

Normal

24 to 38 days

Frequent

< 24 days

Regularity (variation of menstrual cycle length, measured over 12 months)

Regular

± 2 to 20 days over 12 months

Irregular

> 20 days over 12 months

Duration of menstruation

Shortened

< 4.5 days

Normal

4.5 to 8 days

Prolonged

> 8 days

Volume (total blood loss each menstrual cycle)

Light

< 5 mL

Normal

5 to 80 mL

Heavy

> 80 mL

Other terms

Amenorrhea

No bleeding for 90 days

Primary amenorrhea

Absent menarche by 15 years of age

Secondary amenorrhea

Amenorrhea for 6 months with previously regular menstrual cycles

Menopause

Amenorrhea for 12 months without other apparent cause

Precocious menstruation

Menarche before 9 years of age


Adapted with permission from Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):389.

Differential Diagnosis

Although the uterus is often the source, any part of the female reproductive tract can result in vaginal bleeding. Women may also mistake bleeding from nongynecologic sites (e.g., bladder, urethra, perineum, anus) as vaginal bleeding. The prevalence of conditions that cause abnormal bleeding varies according to age. For example, anovulation is more common in adolescents and perimenopausal women, whereas the prevalence of structural lesions and malignancy increases with age.8  The differential diagnosis of abnormal uterine bleeding is presented in Table 2.911

 Enlarge     Print

TABLE 2

Differential Diagnosis of Abnormal Uterine Bleeding

Uterine bleeding

Coagulopathies

Factor deficiencies

Platelet dysfunction   

Thrombocytopenia   

von Willebrand disease   

Iatrogenic

Anticoagulants   

Antidepressants   

Antipsychotics   

Chemotherapeutic agents   

Copper intrauterine device   

Corticosteroids   

Hormonal contraception or other hormone therapy   

Phenytoin (Dilantin)      

Tamoxifen      

Infection      

Acute or chronic endometritis

Pelvic inflammatory disease

Ovulatory dysfunction

Androgen excess

Androgen insensitivity syndrome

Hormone-producing tumors

Polycystic ovary syndrome

Hypothalamic-pituitary-adrenal axis dysfunction

Congenital adrenal hyperplasia

Cushing syndrome/disease

Hyperprolactinemia

Immature hypothalamic-pituitary-adrenal axis (adolescence)

Intense exercise, stress

Lactational amenorrhea

Ovarian follicle decline (perimenopause)

Starvation (including eating disorders)

Thyroid disorders

Tumors, radiation, or trauma of the pituitary/hypothalamus area

Premature ovarian failure

Pregnancy

Abortion

Abruption

Ectopic pregnancy

Gestational trophoblastic disease

Subchorionic hemorrhage

Structural

Adenomyosis

Arteriovenous malformations

Cesarean scar defect

Endometriosis

Leiomyomas

Malignancy

Endometrial hyperplasia/carcinoma

Metastasis

Uterine sarcoma

Outflow obstruction

Polyp

Nonuterine bleeding

Adnexa

Malignancy

Pelvic inflammatory disease

Anus

Anal fissure

Hemorrhoids

Inflammatory bowel disease

Upper or lower gastrointestinal bleeding

Bladder/ureters/kidneys

Infection

Malignancy

Nephrolithiasis

Cervix

Dysplasia/malignancy

Ectropion

Endometritis

Infection (e.g., gonorrhea, chlamydia)

Polyps

Urethra

Urethral diverticula

Urethral prolapse

Urethritis

Vagina

Atrophy

Benign growths

Infection

Retained foreign body

Trauma

Ulcerative conditions

Vulva

Benign growths

Blistering diseases

Malignancy

Trauma

Other

Chronic kidney disease

Chronic liver disease

Diabetes mellitus

Leukemia

Sarcoidosis of the reproductive tract

Tuberculosis of the reproductive tract

Turner syndrome


Information from references 9 through 11.

TABLE 2

Differential Diagnosis of Abnormal Uterine Bleeding

Uterine bleeding

Coagulopathies

Factor deficiencies

Platelet dysfunction   

Thrombocytopenia   

von Willebrand disease   

Iatrogenic

Anticoagulants   

Antidepressants   

Antipsychotics   

Chemotherapeutic agents   

Copper intrauterine device   

Corticosteroids   

Hormonal contraception or other hormone therapy   

Phenytoin (Dilantin)      

Tamoxifen      

Infection      

Acute or chronic endometritis

Pelvic inflammatory disease

Ovulatory dysfunction

Androgen excess

Androgen insensitivity syndrome

Hormone-producing tumors

Polycystic ovary syndrome

Hypothalamic-pituitary-adrenal axis dysfunction

Congenital adrenal hyperplasia

Cushing syndrome/disease

Hyperprolactinemia

Immature hypothalamic-pituitary-adrenal axis (adolescence)

Intense exercise, stress

Lactational amenorrhea

Ovarian follicle decline (perimenopause)

Starvation (including eating disorders)

Thyroid disorders

Tumors, radiation, or trauma of the pituitary/hypothalamus area

Premature ovarian failure

Pregnancy

Abortion

Abruption

Ectopic pregnancy

Gestational trophoblastic disease

Subchorionic hemorrhage

Structural

Adenomyosis

Arteriovenous malformations

Cesarean scar defect

Endometriosis

Leiomyomas

Malignancy

Endometrial hyperplasia/carcinoma

Metastasis

Uterine sarcoma

Outflow obstruction

Polyp

Nonuterine bleeding

Adnexa

Malignancy

Pelvic inflammatory disease

Anus

Anal fissure

Hemorrhoids

Inflammatory bowel disease

Upper or lower gastrointestinal bleeding

Bladder/ureters/kidneys

Infection

Malignancy

Nephrolithiasis

Cervix

Dysplasia/malignancy

Ectropion

Endometritis

Infection (e.g., gonorrhea, chlamydia)

Polyps

Urethra

Urethral diverticula

Urethral prolapse

Urethritis

Vagina

Atrophy

Benign growths

Infection

Retained foreign body

Trauma

Ulcerative conditions

Vulva

Benign growths

Blistering diseases

Malignancy

Trauma

Other

Chronic kidney disease

Chronic liver disease

Diabetes mellitus

Leukemia

Sarcoidosis of the reproductive tract

Tuberculosis of the reproductive tract

Turner syndrome


Information from references 9 through 11.

The most common causes of abnormal uterine bleeding are described with the acronym PALM-COEIN.5 The etiologies in the PALM group (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia) are structural and can be imaged or biopsied. The etiologies in the COEIN group (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified) are nonstructural. These etiologies are not mutually exclusive, and patients may have more than one cause.

POLYP

The lifetime prevalence of endometrial polyps ranges from 8% to 35%, and their incidence increases with age.12 Intermenstrual bleeding is the most common presenting symptom, but many polyps are asymptomatic. Physical examination findings are typically unremarkable, except for cases in which the polyps prolapse through the cervix.13 Although they can develop into malignancy, approximately 95% of symptomatic polyps are benign, and the risk of malignancy is even lower in premenopausal women.14

ADENOMYOSIS

The presence of endometrial tissue in the myometrium is known as adenomyosis. Its prevalence ranges from 5% to 70%, and its association with abnormal uterine bleeding is unclear.15 Many patients are asymptomatic, but those who have symptoms typically report painful, heavy, or prolonged menstrual bleeding. Examination may reveal a dense, enlarged uterus.

LEIOMYOMA

Leiomyomas (also called fibroids) are benign tumors arising from the uterine myometrium. Their prevalence increases with age; they are eventually found in up to 80% of all women.16 Most leiomyomas are asymptomatic, but bleeding is a common presenting symptom and typically involves heavy or prolonged menses. Larger leiomyomas are more likely to be associated with abnormal uterine bleeding.17 Patients may report pelvic pain or pressure, and on examination the uterus may be enlarged or irregularly contoured. More information on the diagnosis and treatment of leiomyomas is available in a previous American Family Physician article (https://www.aafp.org/afp/2017/0115/p100.html).

MALIGNANCY AND HYPERPLASIA

Abnormal uterine bleeding is the most common symptom of endometrial cancer.18 Although the prevalence of endometrial cancer increases with age, close to one-fourth of new diagnoses occur in patients younger than 55 years.19  Long-term unopposed estrogen exposure is the primary risk factor (Table 3).18,20 Bleeding patterns in patients with uterine malignancy are highly variable. More information on the diagnosis and management of endometrial cancer is available in a previous American Family Physician article (https://www.aafp.org/afp/2016/0315/p468.html).

 Enlarge     Print

TABLE 3

Risk Factors for Endometrial Cancer

Risk factorRelative risk

Major

Long-term use of unopposed estrogen

10 to 20

Hereditary nonpolyposis colorectal cancer (Lynch syndrome)

6 to 20

Estrogen-producing tumor

> 5

Minor

Obesity

2 to 5

Nulliparity

3

Polycystic ovary syndrome

3

History of infertility

2 to 3

Late menopause

2 to 3

Tamoxifen use

2 to 3

Type 2 diabetes mellitus, hypertension, gallbladder disease, or thyroid disease

1.3 to 3


Information from references 18 and 20.

TABLE 3

Risk Factors for Endometrial Cancer

Risk factorRelative risk

Major

Long-term use of unopposed estrogen

10 to 20

Hereditary nonpolyposis colorectal cancer (Lynch syndrome)

6 to 20

Estrogen-producing tumor

> 5

Minor

Obesity

2 to 5

Nulliparity

3

Polycystic ovary syndrome

3

History of infertility

2 to 3

Late menopause

2 to 3

Tamoxifen use

2 to 3

Type 2 diabetes mellitus, hypertension, gallbladder disease, or thyroid disease

1.3 to 3


Information from references 18 and 20.

COAGULOPATHY

Approximately 20% of patients with heavy menstrual bleeding have a bleeding disorder, and the prevalence in adolescent girls who bleed heavily is even higher.2123 Von Willebrand disease and platelet dysfunction are the most common coagulopathies associated with abnormal uterine bleeding.24 In addition to heavy menstrual bleeding, adolescents with bleeding disorders may report irregular menstrual bleeding.25

OVULATORY DYSFUNCTION

A variety of endocrine disorders can lead to ovulatory dysfunction (Table 2).911 Infrequent or absent ovulation during the first few years after menarche and during perimenopause is common and not necessarily a sign of underlying pathology.26 Menstrual bleeding caused by ovulatory dysfunction is often irregular, heavy, or prolonged.

ENDOMETRIAL

Primary disorders of endometrial hemostasis typically occur in the setting of predictable ovulatory cycles and are likely due to vasoconstriction disorders, inflammation, or infection. Endometrial dysfunction is poorly understood; there are no reliable diagnostic methods, and it should be considered only after other causes are excluded.5

IATROGENIC

A variety of medical treatments can provoke abnormal uterine bleeding. Hormonal contraception is the most common cause of iatrogenic uterine bleeding (i.e., breakthrough bleeding).5 Other causative agents include noncontraceptive hormone therapy, drugs that interfere with sex steroid hormone function or synthesis (e.g., tamoxifen), anticoagulants, and dopamine antagonists (e.g., tricyclic antidepressants, some antipsychotics).

NOT OTHERWISE CLASSIFIED

This category contains poorly understood conditions, rare disorders (e.g., arteriovenous malformations), and conditions that do not otherwise fit into the classification system, such as cesarean scar defects, which can cause postmenstrual spotting when blood collects in the niche caused by the scar.

Diagnostic Evaluation

The approach to patients presenting with abnormal uterine bleeding includes assessing for hemodynamic instability and anemia, identifying the source of bleeding, pregnancy testing, and determining whether evaluation for endometrial carcinoma is indicated (Figure 1).6,18,2630 The broad differential diagnosis necessitates a detailed history and physical examination.

FIGURE 1

Evaluation and management of abnormal uterine bleeding.

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

†—Risk factors include a history of exposure to unopposed estrogen (Table 3), failed medical management, and persistent bleeding.

‡—Initial screening tests may be normal in the setting of some coagulopathies, with diagnosis requiring further testing and possibly hematology consultation.

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


FIGURE 1

Evaluation and management of abnormal uterine bleeding.

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

†—Risk factors include a history of exposure to unopposed estrogen (Table 3), failed medical management, and persistent bleeding.

‡—Initial screening tests may be normal in the setting of some coagulopathies, with diagnosis requiring further testing and possibly hematology consultation.

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

BLEEDING HISTORY

A description of the bleeding pattern should be elicited, including frequency, duration, regularity, and volume. Heavy menstrual bleeding is defined as more than 80 mL of total blood loss, but quantitative assessment is impractical in routine clinical practice. Historical clues such as passing blood clots or changing pads/tampons at least hourly suggest heavy menstrual bleeding.31 A history of postcoital bleeding may indicate cervicitis, ectropion, or, rarely, cervical cancer, whereas abdominopelvic pain may suggest infection, structural lesions, or endometriosis.

Clinicians may underestimate the prevalence of coagulopathies among patients with abnormal uterine bleeding.32 These conditions should be considered in women with a family history of abnormal bleeding or a personal history of heavy menstrual bleeding since menarche, or symptoms such as frequent bruising, bleeding gums, epistaxis, postpartum hemorrhage, or bleeding with surgical and dental procedures.27

PHYSICAL EXAMINATION

An examination of the pelvis, including speculum and bimanual examinations, is an important aspect of the evaluation of abnormal uterine bleeding. Care should be taken to examine all potential bleeding sites, including the urethra, perineum, and anus. Cervical cancer screening should be performed if it is not up to date. Pelvic examination can be deferred in adolescents if the patient is not sexually active, neither trauma nor infection is suspected, and the response to initial treatment is adequate.33

LABORATORY TESTING

All patients with abnormal uterine bleeding should be evaluated for pregnancy with a urine or serum human chorionic gonadotropin test, and for anemia and thrombocytopenia with a complete blood count.6 Thyroid function should be evaluated in patients with signs or symptoms of thyroid disease, or if the initial workup does not reveal a likely cause.6,28,34 Additional hormonal tests (e.g., prolactin, androgens, estrogen) are indicated only if history or examination findings suggest a specific hormonal cause.26,28 The platelet count, prothrombin time, and partial thromboplastin time can be initial screening tests when a bleeding disorder is suspected, but results may be normal in women with von Willebrand disease or other bleeding disorders. Diagnosing a bleeding disorder typically requires additional testing, often in consultation with a hematologist.27

Because older age is an important risk factor for endometrial cancer, all patients with abnormal uterine bleeding who are 45 years or older should undergo endometrial sampling.18 Younger women should undergo sampling if they have a history of unopposed estrogen exposure, if medical management fails, or if bleeding symptoms persist.6 Office-based endometrial biopsy is the preferred approach, with hysteroscopic dilation and curettage reserved for instances in which office sampling fails, is inadequate, or cannot be performed.35 Blind sampling may miss focal lesions, so hysteroscopic dilation and curettage should be performed if symptoms persist despite normal biopsy results.18

IMAGING

Indications for pelvic imaging include abnormalities palpated on bimanual examination or symptoms that persist despite initial treatment.6 Transvaginal ultrasonography is the first-line approach for most patients, although saline infusion sonohysterography (the infusion of sterile saline into the endometrial cavity while transvaginal ultrasonography is performed) is better at detecting intracavitary lesions.36 Routine use of magnetic resonance imaging is discouraged but can be considered if sonographic imaging is inadequate.6

Management

Multiple factors should be considered when choosing among treatment options for abnormal uterine bleeding (Table 4),3742 including the cause and acuity of the bleeding, fertility and contraceptive preferences, medical comorbidities, adverse effects, cost, and relative effectiveness. If the underlying cause of bleeding can be identified and treated, symptoms may resolve without the need for additional intervention. Anemia is an indication for treatment, as is bleeding that negatively affects the patient's quality of life. Because exposure to unopposed estrogen increases the risk of endometrial cancer, treatment of anovulatory abnormal uterine bleeding involves inducing ovulatory cycles or administering supplemental progesterone to antagonize estrogen's proliferative effect on the endometrium.

 Enlarge     Print

TABLE 4

Treatment Options for Medical Management of Abnormal Uterine Bleeding

DrugSuggested dosageNotes

Acute bleeding

Conjugated equine estrogen

Hemodynamically unstable: 25 mg intravenously every 4 to 6 hours for up to 24 hours

Follow treatment with a progestin to provoke withdrawal bleeding; do not use in patients at increased risk of thrombosis

Hemodynamically stable: 2.5 mg orally every 6 hours for 21 days

Estrogen-progestin oral contraceptives

1 monophasic pill containing 35 mcg of ethinyl estradiol orally 3 times daily for 7 days

Other regimens also effective; do not use in patients at increased risk of thrombosis

Progestins

Norethindrone, 5 mg orally 3 times daily for 7 days

Other high-dose oral progestins are also effective

Tranexamic acid

10 mg per kg intravenously every 8 hours or 20 to 25 mg per kg orally every 8 hours

Faster onset if given intravenously; do not use in patients at increased risk of thrombosis

Chronic bleeding

Depot medroxyprogesterone (Depo-Provera)

150 mg intramuscularly or 104 mg subcutaneously every 13 weeks

Unscheduled bleeding is a common initial adverse effect, but one-half of patients become amenorrheic after 12 months of use

Estrogen-progestin oral contraceptives

1 monophasic pill containing 35 mcg of ethinyl estradiol daily

Other routes (transdermal patch, intravaginal ring) are likely also effective; regimens with no or fewer hormone-free intervals may be more effective

Levonorgestrel

52-mg (20-mcg-per-day) intrauterine device (Mirena)

Effectiveness data are based primarily on trials involving the 20-mcg-per-day device; effect on bleeding suppression may wane before contraceptive effectiveness expires

Nonsteroidal anti-inflammatory drugs

Naproxen, 500 mg orally 2 times daily

Other oral nonsteroidal anti-inflammatory drugs are also effective; administer only while patient is bleeding; do not use in patients with coagulopathy

Progestins

Norethindrone, 2.5 to 5 mg orally once daily

Other oral progestins are also effective; administration during only the luteal phase is significantly less effective for treating heavy bleeding

Tranexamic acid (Lysteda)

1,000 to 1,500 mg orally 3 times daily

Faster onset if given intravenously; do not use in patients at increased risk of thrombosis


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

Information from references 37 through 42.

TABLE 4

Treatment Options for Medical Management of Abnormal Uterine Bleeding

DrugSuggested dosageNotes

Acute bleeding

Conjugated equine estrogen

Hemodynamically unstable: 25 mg intravenously every 4 to 6 hours for up to 24 hours

Follow treatment with a progestin to provoke withdrawal bleeding; do not use in patients at increased risk of thrombosis

Hemodynamically stable: 2.5 mg orally every 6 hours for 21 days

Estrogen-progestin oral contraceptives

1 monophasic pill containing 35 mcg of ethinyl estradiol orally 3 times daily for 7 days

Other regimens also effective; do not use in patients at increased risk of thrombosis

Progestins

Norethindrone, 5 mg orally 3 times daily for 7 days

Other high-dose oral progestins are also effective

Tranexamic acid

10 mg per kg intravenously every 8 hours or 20 to 25 mg per kg orally every 8 hours

Faster onset if given intravenously; do not use in patients at increased risk of thrombosis

Chronic bleeding

Depot medroxyprogesterone (Depo-Provera)

150 mg intramuscularly or 104 mg subcutaneously every 13 weeks

Unscheduled bleeding is a common initial adverse effect, but one-half of patients become amenorrheic after 12 months of use

Estrogen-progestin oral contraceptives

1 monophasic pill containing 35 mcg of ethinyl estradiol daily

Other routes (transdermal patch, intravaginal ring) are likely also effective; regimens with no or fewer hormone-free intervals may be more effective

Levonorgestrel

52-mg (20-mcg-per-day) intrauterine device (Mirena)

Effectiveness data are based primarily on trials involving the 20-mcg-per-day device; effect on bleeding suppression may wane before contraceptive effectiveness expires

Nonsteroidal anti-inflammatory drugs

Naproxen, 500 mg orally 2 times daily

Other oral nonsteroidal anti-inflammatory drugs are also effective; administer only while patient is bleeding; do not use in patients with coagulopathy

Progestins

Norethindrone, 2.5 to 5 mg orally once daily

Other oral progestins are also effective; administration during only the luteal phase is significantly less effective for treating heavy bleeding

Tranexamic acid (Lysteda)

1,000 to 1,500 mg orally 3 times daily

Faster onset if given intravenously; do not use in patients at increased risk of thrombosis


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

Information from references 37 through 42.

EMERGENT TREATMENT

Occasionally, abnormal uterine bleeding is of sufficient quantity or duration that emergent attention is required. For hemodynamically unstable patients, uterine tamponade using a Foley catheter or gauze packing can achieve rapid but temporary control of blood loss.43 Further emergency interventions for hemodynamically unstable patients include intravenous estrogen, dilation and curettage, uterine artery embolization, and, rarely, hysterectomy. Medical therapy (e.g., oral estrogen, combined oral contraceptives, oral progestins, intravenous tranexamic acid) is usually adequate for treating hemodynamically stable patients with severe bleeding.

NONEMERGENT TREATMENT

A wider range of medical and surgical options are available for treatment of nonemergent uterine bleeding (Table 4).3742 To avoid surgical risks and preserve fertility, medical management is the first-line approach for most patients.44 Among medical therapies, the 20-mcg-per-day formulation of the levonorgestrel-releasing intrauterine system (Mirena) is most effective for decreasing heavy menstrual bleeding (71% to 95% reduction in blood loss) and is as effective as hysterectomy when quality-adjusted life years are considered.39,4547 Estrogen-progestin oral contraceptives are effective (35% to 69% reduction) and can also be used to regulate bleeding in patients with ovulatory dysfunction.39,48 Continuous dosing of oral progestins is another effective hormonal treatment option (87% reduction), but long-term patient satisfaction is low.39,49 Two effective, well-tolerated, nonhormonal choices are oral tranexamic acid (Lysteda; 26% to 54% reduction) and nonsteroidal anti-inflammatory drugs (10% to 52% reduction).39,50 Both are taken only when the patient is bleeding, and tranexamic acid has the added benefit of being safe while the patient is attempting to conceive.

Hysterectomy is the definitive and most effective treatment for abnormal uterine bleeding, and it yields a high level of patient satisfaction.44,47,51 A less invasive, lower-risk surgical option is endometrial ablation, which is as effective as the levonorgestrel-releasing intrauterine system.47 A variety of ablative techniques are available, and all are equivalent in terms of bleeding outcomes and patient satisfaction.52 Myomectomy and uterine artery embolization are treatment options for leiomyomas, and endometrial polyps can be treated with polypectomy. Except for myomectomy and polypectomy, surgical interventions for abnormal uterine bleeding are contraindicated in patients who wish to preserve fertility.

This article updates previous articles on this topic by Sweet, et al.53; Albers, et al.54; and Oriel and Schrager.55

Data Sources: A PubMed search was completed in Clinical Queries using the key terms abnormal uterine bleeding, heavy menstrual bleeding, irregular menstrual bleeding, menorrhagia, metrorrhagia, and dysfunctional uterine bleeding. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Also searched were the Agency for Healthcare Research and Quality evidence reports, Clinical Evidence, the Cochrane database, and UpToDate. Search dates: August 21, 2017, and November 10, 2018.

The Authors

show all author info

NOAH WOUK, MD, is a family medicine physician at Piedmont Health Services, Prospect Hill, N.C., and an adjunct assistant professor in the Department of Family Medicine at the University of North Carolina School of Medicine, Chapel Hill...

MARGARET HELTON, MD, is a professor in the Department of Family Medicine at the University of North Carolina School of Medicine.

Address correspondence to Noah Wouk, MD, Piedmont Health Services, 322 Main St., Prospect Hill, NC 27314 (e-mail: woukno@piedmonthealth.org). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health. 2007;10(3):183–194....

2. Frick KD, Clark MA, Steinwachs DM, et al.; STOP-DUB Research Group. Financial and quality-of-life burden of dysfunctional uterine bleeding among women agreeing to obtain surgical treatment. Womens Health Issues. 2009;19(1):70–78.

3. Barnard K, Frayne SM, Skinner KM, Sullivan LM. Health status among women with menstrual symptoms. J Womens Health (Larchmt). 2003;12(9):911–919.

4. Côté I, Jacobs P, Cumming DC. Use of health services associated with increased menstrual loss in the United States. Am J Obstet Gynecol. 2003;188(2):343–348.

5. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3–13.

6. Committee on Practice Bulletins—Gynecology. Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012;120(1):197–206.

7. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):383–390.

8. Ahuja SP, Hertweck SP. Overview of bleeding disorders in adolescent females with menorrhagia. J Pediatr Adolesc Gynecol. 2010;23(6 suppl):S15–S21.

9. Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. Williams Gynecology. 3rd ed. New York, NY: McGraw-Hill Education; 2016.

10. Brenner PF. Differential diagnosis of abnormal uterine bleeding. Am J Obstet Gynecol. 1996;175(3 pt 2):766–769.

11. Kaunitz A. Differential diagnosis of genital tract bleeding in women. UpToDate. October 31, 2017. https://www.uptodate.com/contents/differential-diagnosis-of-genital-tract-bleeding-in-women [subscription required]. Accessed August 19, 2018.

12. Salim S, Won H, Nesbitt-Hawes E, Campbell N, Abbott J. Diagnosis and management of endometrial polyps: a critical review of the literature. J Minim Invasive Gynecol. 2011;18(5):569–581.

13. Lieng M, Istre O, Sandvik L, Qvigstad E. Prevalence, 1-year regression rate, and clinical significance of asymptomatic endometrial polyps: cross-sectional study. J Minim Invasive Gynecol. 2009;16(4):465–471.

14. Baiocchi G, Manci N, Pazzaglia M, et al. Malignancy in endometrial polyps: a 12-year experience. Am J Obstet Gynecol. 2009;201(5):462.e1–462.e4.

15. Taran FA, Stewart EA, Brucker S. Adenomyosis: epidemiology, risk factors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd. 2013;73(9):924–931.

16. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188(1):100–107.

17. Wegienka G, Baird DD, Hertz-Picciotto I, et al. Self-reported heavy bleeding associated with uterine leiomyomata. Obstet Gynecol. 2003;101(3):431–437.

18. Practice bulletin no. 149: endometrial cancer. Obstet Gynecol. 2015;125(4):1006–1026.

19. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer stat facts: uterine cancer. https://seer.cancer.gov/statfacts/html/corp.html. Accessed November 11, 2017.

20. Coulam CB, Annegers JF, Kranz JS. Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol. 1983;61(4):403–407.

21. Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet. 1998;351(9101):485–489.

22. Mikhail S, Varadarajan R, Kouides P. The prevalence of disorders of haemostasis in adolescents with menorrhagia referred to a haemophilia treatment centre. Haemophilia. 2007;13(5):627–632.

23. Knol HM, Mulder AB, Bogchelman DH, Kluin-Nelemans HC, van der Zee AG, Meijer K. The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities. Am J Obstet Gynecol. 2013;209(3):202.e1–202.e7.

24. Munro MG, Lukes AS; Abnormal Uterine Bleeding and Underlying Hemostatic Disorders Consensus Group. Abnormal uterine bleeding and underlying hemostatic disorders: report of a consensus process. Fertil Steril. 2005;84(5):1335–1337.

25. Vo KT, Grooms L, Klima J, Holland-Hall C, O'Brien SH. Menstrual bleeding patterns and prevalence of bleeding disorders in a multidisciplinary adolescent haematology clinic. Haemophilia. 2013;19(1):71–75.

26. Committee on Practice Bulletins—Gynecology. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176–185.

27. Kouides PA, Conard J, Peyvandi F, Lukes A, Kadir R. Hemostasis and menstruation: appropriate investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil Steril. 2005;84(5):1345–1351.

28. National Institute for Health and Care Excellence. Heavy menstrual bleeding: assessment and management. Clinical guideline [CG44]. Updated August 2016. https://www.nice.org.uk/guidance/cg44. Accessed August 31, 2017.

29. Zacur HA. Managing an episode of severe or prolonged uterine bleeding. UpToDate. August 23, 2016. https://www.uptodate.com/contents/managing-an-episode-of-severe-or-prolonged-uterine-bleeding [subscription required]. Accessed August 19, 2018.

30. Marret H, Fauconnier A, Chabbert-Buffet N, et al.; CNGOF Collège National des Gynécologues et Obstétriciens Français. Clinical practice guidelines on menorrhagia: management of abnormal uterine bleeding before menopause. Eur J Obstet Gynecol Reprod Biol. 2010;152(2):133–137.

31. Warner PE, Critchley HO, Lumsden MA, Campbell-Brown M, Douglas A, Murray GD. 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(5):1216–1223.

32. Dilley A, Drews C, Lally C, Austin H, Barnhart E, Evatt B. A survey of gynecologists concerning menorrhagia: perceptions of bleeding disorders as a possible cause. J Womens Health Gend Based Med. 2002;11(1):39–44.

33. Braverman PK, Breech L; Committee on Adolescence. American Academy of Pediatrics. Clinical report—gynecologic examination for adolescents in the pediatric office setting. Pediatrics. 2010;126(3):583–590.

34. Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50(5):655–659.

35. Ronghe R, Gaudoin M. Women with recurrent postmenopausal bleeding should be re-investigated but are not more likely to have endometrial cancer. Menopause Int. 2010;16(1):9–11.

36. Wheeler KC, Goldstein SR. Transvaginal ultrasound for the diagnosis of abnormal uterine bleeding. Clin Obstet Gynecol. 2017;60(1):11–17.

37. Arias RD, Jain JK, Brucker C, Ross D, Ray A. Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous injection 104 mg. Contraception. 2006;74(3):234–238.

38. Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial. Obstet Gynecol. 2006;108(4):924–929.

39. Matteson KA, Rahn DD, Wheeler TL II, et al.; Society of Gynecologic Surgeons Systematic Review Group. Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol. 2013;121(3):632–643.

40. Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014;(7):CD004695.

41. Bradley LD, Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016;214(1):31–44.

42. ACOG committee opinion no. 557: management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891–896.

43. James AH, Kouides PA, Abdul-Kadir R, et al. Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):124–134.

44. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev. 2016;(1):CD003855.

45. Gupta J, Kai J, Middleton L, Pattison H, Gray R, Daniels J, et al. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. N Engl J Med. 2013;368(2):128–137.

46. Heliövaara-Peippo S, Hurskainen R, Teperi J, et al. Quality of life and costs of levonorgestrel-releasing intrauterine system or hysterectomy in the treatment of menorrhagia: a 10-year randomized controlled trial. Am J Obstet Gynecol. 2013;209(6):535.e1–535.e14.

47. Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2015;(4):CD002126.

48. Davis A, Godwin A, Lippman J, Olson W, Kafrissen M. Triphasic norg-estimate-ethinyl estradiol for treating dysfunctional uterine bleeding. Obstet Gynecol. 2000;96(6):913–920.

49. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkilä A, Walker JJ, Cameron IT. Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. Br J Obstet Gynaecol. 1998;105(6):592–598.

50. Hartmann KE, Jerome RN, Lindegren ML, et al.; Effective Health Care Program; Agency for Healthcare Research and Quality. Primary care management of abnormal uterine bleeding. Comparative effectiveness review no. 96. Rockville, Md.: Agency for Healthcare Research and Quality; 2013.

51. Cozza G, Pinto A, Giovanale V, et al. Comparative effectiveness and impact on health-related quality of life of hysterectomy vs. levonorgestrel intra-uterine system for abnormal uterine bleeding. Eur Rev Med Pharmacol Sci. 2017;21(9):2255–2260.

52. Lethaby A, Penninx J, Hickey M, Garry R, Marjoribanks J. Endometrial resection and ablation techniques for heavy menstrual bleeding. Cochrane Database Syst Rev. 2013;(8):CD001501.

53. Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP. Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2012;85(1):35–43.

54. Albers JR, Hull SK, Wesley RM. Abnormal uterine bleeding. Am Fam Physician. 2004;69(8):1915–1926.

55. Oriel KA, Schrager S. Abnormal uterine bleeding. Am Fam Physician. 1999;60(5):1371–1380.

 

 

Copyright © 2019 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Sep 15, 2020

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article