Abnormal Uterine Bleeding in Premenopausal Women 2019 AAFP PDF

Abnormal Uterine Bleeding in Premenopausal Women Noah Wouk, MD, Piedmont Health Services, Prospect Hill, North Carolina Margaret Helton, MD, University of North Carolina School of Medicine, Cha...

Abnormal Uterine Bleeding in Premenopausal Women Noah Wouk, MD, Piedmont Health Services, Prospect Hill, North Carolina Margaret Helton, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina Abnormal uterine bleeding is a common symptom in women. The acronym PALM-COEIN facilitates classification, with PALM referring to structural etiologies (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia), and COEIN referring to non- structural etiologies (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified). Evaluation involves a detailed history and pelvic examination, as well as laboratory testing that includes a pregnancy test and complete blood count. Endometrial sampling should be performed in patients 45 years and older, and in younger patients with a sig- nificant history of unopposed estrogen exposure. Transvaginal ultrasonography is the preferred imaging modality and is indicated if a structural etiology is suspected or if symptoms persist despite appropriate initial treatment. Medical and surgical treatment options are available. Emergency interventions for severe bleeding that causes hemodynamic instability include uterine tamponade, intravenous estrogen, dilation and curettage, and uterine artery embolization. To avoid surgical risks and preserve fertility, medical management is the preferred initial approach for hemodynamically stable patients. Patients with severe bleeding can be treated initially with oral estrogen, high-dose estrogen-progestin oral contraceptives, oral pro- gestins, or intravenous tranexamic acid. The most effective long-term medical treatment for heavy menstrual bleeding is the levonorgestrel-releasing intrauterine system. Other long-term medical treatment options include estrogen-progestin oral contraceptives, oral progestins, oral tranexamic acid, nonsteroidal anti-inflammatory drugs, and depot medroxyprogester- one. Hysterectomy is the definitive treatment. A lower-risk surgical option is endometrial ablation, which performs as well as the levonorgestrel-releasing intrauterine system. Select patients with chronic uterine bleeding can be treated with myo- mectomy, polypectomy, or uterine artery embolization. (Am Fam Physician. 2019;99(7):435-443. Copyright © 2019 American Academy of Family Physicians.) Abnormal uterine bleeding is a common condition, Definitions with a prevalence of 10% to 30% among women of reproduc- Abnormal uterine bleeding is a symptom, not a diagnosis; tive age.1 It negatively affects quality of life and is associated the term is used to describe bleeding that falls outside pop- with financial loss, decreased productivity, poor health, and ulation-based 5th to 95th percentiles for menstrual regular- increased use of health care resources.2-4 In 2011 the Interna- ity, frequency, duration, and volume (Table 1).7 Abnormal tional Federation of Gynecology and Obstetrics convened a bleeding is considered chronic when it has occurred for working group that produced standardized definitions and most of the previous six months, or acute when an episode classifications for menstrual disorders, which the American of heavy bleeding warrants immediate intervention.5 Inter- College of Obstetricians and Gynecologists subsequently menstrual bleeding is bleeding that occurs between oth- - endorsed.5,6 The updated terminology pertains only to non- erwise normal menstrual periods.7 Use of imprecise terms pregnant women of reproductive age, which is the scope of such as menorrhagia, metrorrhagia, and dysfunctional this review. uterine bleeding is now discouraged. * Differential Diagnosis Additional content available at https://www.aafp.org/ Although the uterus is often the source, any part of the afp/2019/0401/p435.html. female reproductive tract can result in vaginal bleeding. CME This clinical content conforms to AAFP criteria for con- tinuing medical education (CME). See CME Quiz on page 418. Women may also mistake bleeding from nongynecologic sites (e.g., bladder, urethra, perineum, anus) as vaginal Author disclosure: No relevant financial affiliations. bleeding. The prevalence of conditions that cause abnormal Patient information: A handout on this topic is available at https://familydoctor.org/condition/ bleeding varies according to age. For example, anovulation is abnormal-uterine-bleeding/. more common in adolescents and perimenopausal women, whereas the prevalence of structural lesions and malignancy Downloaded from April 1, 2019 the American ◆ Volume Family Physician 99, Number 7 website at www.aafp.org/afp. Copyright © 2019 American Academy of Family www.aafp.org/afp American Family Physicians. Physician For the 435 private, noncom- mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.  ABNORMAL UTERINE BLEEDING increases with age.8 The differential diagnosis of abnormal WHAT IS NEW ON THIS TOPIC uterine bleeding is presented in Table 2.9-11 The most common causes of abnormal uterine bleeding Abnormal Uterine Bleeding are described with the acronym PALM-COEIN.5 The eti- The acronym PALM-COEIN facilitates the classification of ologies in the PALM group (polyp, adenomyosis, leiomy- abnormal uterine bleeding, with PALM referring to structural oma, malignancy and hyperplasia) are structural and can etiologies (polyp, adenomyosis, leiomyoma, malignancy and be imaged or biopsied. The etiologies in the COEIN group hyperplasia), and COEIN referring to nonstructural etiologies (coagulopathy, ovulatory dysfunction, endometrial, iatro- (coagulopathy, ovulatory dysfunction, endometrial, iatro- genic, not otherwise classified). genic, not otherwise classified) are nonstructural. These etiologies are not mutually exclusive, and patients may have Among medical therapies, the 20-mcg-per-day formulation more than one cause. G of the levonorgestrel-releasing intrauterine system (Mirena) is most effective for decreasing heavy menstrual bleeding (71% to 95% reduction in blood loss) and performs similarly to POLYP The lifetime prevalence of endometrial polyps ranges hysterectomy when quality-adjusted life years are considered. from 8% to 35%, and their incidence increases with age.12 Intermenstrual bleeding is the most common presenting symptom, but TABLE 1 many polyps are asymptomatic. Phys- ical examination findings are typically Definitions of Normal and Abnormal Menstrual Bleeding unremarkable, except for cases in Menstrual cycle terms Descriptive terms Definition which the polyps prolapse through the cervix.13 Although they can develop Frequency (interval Infrequent > 38 days between the start of each into malignancy, approximately 95% menstrual cycle) Normal 24 to 38 days of symptomatic polyps are benign, and Frequent < 24 days the risk of malignancy is even lower in premenopausal women.14 Regularity (variation of Regular ± 2 to 20 days over 12 months menstrual cycle length, Irregular > 20 days over 12 months ADENOMYOSIS measured over 12 months) The presence of endometrial tissue Duration of menstruation Shortened < 4.5 days in the myometrium is known as ade- Normal 4.5 to 8 days nomyosis. Its prevalence ranges from 5% to 70%, and its association with Prolonged > 8 days abnormal uterine bleeding is unclear.15 Volume (total blood loss Light < 5 mL Many patients are asymptomatic, but each menstrual cycle) Normal 5 to 80 mL those who have symptoms typically report painful, heavy, or prolonged Heavy > 80 mL menstrual bleeding. Examination may Other terms Amenorrhea No bleeding for 90 days reveal a dense, enlarged uterus. Primary Absent menarche by 15 years LEIOMYOMA amenorrhea of age Leiomyomas (also called fibroids) are Secondary Amenorrhea for 6 months with benign tumors arising from the uter- amenorrhea previously regular menstrual cycles ine myometrium. Their prevalence Menopause Amenorrhea for 12 months with- increases with age; they are eventually out other apparent cause found in up to 80% of all women.16 Precocious Menarche before 9 years of age Most leiomyomas are asymptomatic, menstruation but bleeding is a common presenting symptom and typically involves heavy Adapted with permission from Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO rec- ommendations on terminologies and definitions for normal and abnormal uterine bleeding. or prolonged menses. Larger leiomy- Semin Reprod Med. 2011;29(5):389. omas are more likely to be associated with abnormal uterine bleeding.17 436 American Family Physician www.aafp.org/afp Volume 99, Number 7 ◆ April 1, 2019  TABLE 2 TABLE 3 Differential Diagnosis of Abnormal Risk Factors for Endometrial Cancer Uterine Bleeding Risk factor Relative risk Coagulopathies Major Iatrogenic Long-term use of unopposed estrogen 10 to 20 Anticoagulants Hereditary nonpolyposis colorectal 6 to 20 Antipsychotics cancer (Lynch syndrome) Copper intrauterine device Estrogen-producing tumor >5 Hormonal contraception or other hormone therapy Tamoxifen Minor Obesity 2 to 5 Infection -not multiparity Acute or chronic endometritis Nulliparity 3 Pelvic inflammatory disease Polycystic ovary syndrome 3 Ovulatory dysfunction History of infertility 2 to 3 early Hyperprolactinemia Immature hypothalamic-pituitary-adrenal axis (adolescence) & Late menopause - not 2 to 3 Intense exercise or stress Tamoxifen use 2 to 3 Ovarian follicle decline (perimenopause) Type 2 diabetes mellitus, hypertension, 1.3 to 3 Polycystic ovary syndrome gallbladder disease, or thyroid disease Starvation (including eating disorders) Information from references 18 and 20. Thyroid disorders Pregnancy Abortion COAGULOPATHY Abruption or subchorionic hemorrhage Approximately 20% of patients with heavy menstrual Ectopic pregnancy bleeding have a bleeding disorder, and the prevalence in adolescent girls who bleed heavily is even higher.21-23 Von Structural Willebrand disease and platelet dysfunction are the most Adenomyosis common coagulopathies associated with abnormal uterine Endometriosis bleeding.24 In addition to heavy menstrual bleeding, ado- Leiomyoma lescents with bleeding disorders may report irregular men- Malignancy or hyperplasia strual bleeding.25 Polyp Information from references 9 through 11. OVULATORY DYSFUNCTION A variety of endocrine disorders can lead to ovulatory dys- function (Table 2).9-11 Infrequent or absent ovulation during Patients may report pelvic pain or pressure, and on exam- the first few years after menarche and during perimeno- ination the uterus may be enlarged or irregularly contoured. pause is common and not necessarily a sign of underlying More information on the diagnosis and treatment of leiomy- pathology.26 Menstrual bleeding caused by ovulatory dys- omas is available in a previous American Family Physician function is often irregular, heavy, or prolonged. article (https://www.aafp.org/afp/2017/0115/p100.html). ENDOMETRIAL MALIGNANCY AND HYPERPLASIA Primary disorders of endometrial hemostasis typically Abnormal uterine bleeding is the most common symptom occur in the setting of predictable ovulatory cycles and are of endometrial cancer.18 Although the prevalence of endo- likely due to vasoconstriction disorders, inflammation, or metrial cancer increases with age, close to one-fourth of infection. Endometrial dysfunction is poorly understood; new diagnoses occur in patients younger than 55 years.19 there are no reliable diagnostic methods, and it should be Long-term unopposed estrogen exposure is the primary considered only after other causes are excluded.5 risk factor (Table 3).18,20 Bleeding patterns in patients with uterine malignancy are highly variable. More information IATROGENIC on the diagnosis and management of endometrial cancer A variety of medical treatments can provoke abnormal is available in a previous American Family Physician article uterine bleeding. Hormonal contraception is the most com- (https://www.aafp.org/afp/2016/0315/p468.html). mon cause of iatrogenic uterine bleeding (i.e., breakthrough April 1, 2019 ◆ Volume 99, Number 7 www.aafp.org/afp American Family Physician 437  ABNORMAL UTERINE BLEEDING FIGURE 1 Initial history or physical examination suggests acute or severe blood loss? No ! A Structured history and physical examination Pregnancy test Complete blood count Cervical cancer screening (if due) Additional evaluation if clinically indicated Address the underlying etiology, if apparent Suspected Age ≥ 45 years Abnormal Infectious cause suspected: Initial treatment options for severe coagulopathy?* or elevated risk bimanual exam- test for gonorrhea, chla- abnormal uterine bleeding in hemo- of endometrial ination findings mydia, trichomoniasis dynamically stable women: carcinoma?† or symptoms that Hormonal cause suspected: persist despite ~ High-dose estrogen-progestin oral Review platelet count; evaluate for anovulation, treatment? contraceptives check prothrom- thyroid disorder, hyperpro- bin time and partial Endometrial lactinemia, polycystic ~High-dose oral progestins thromboplastin time biopsy ovary syndrome ~Intravenous tranexamic acid Transvaginal ~Endometrial ablation ultrasonography Long-term medical therapy options: Abnormal, or coag- Abnormal Positive or abnormal Levonorgestrel-releasing intrauterine ulopathy strongly ~ system (Mirena) suspected‡ Abnormal ~Estrogen-progestin oral contraceptives ~Oral progestins -Oral tranexamic acid (Lysteda) ~ Nonsteroidal anti-inflammatory drugs Further evaluation and treatment as indicated ~Depot medroxyprogesterone (Depo-Provera) Long-term surgical options: Endometrial ablation Uterine artery embolization Hysterectomy Evaluation and management of abnormal uterine bleeding. *—The likelihood of a bleeding disorder increases if any of the following historical clues are present: heavy menstrual bleeding since menarche; history of postpartum hemorrhage, surgical bleeding, or bleeding with dental procedures; or two or more of the following: frequent gum bleeding, bruising > 5 cm at least monthly, epistaxis at least monthly, or family history of abnormal bleeding. 25 Information from references 6, 18, and 26 through 30. bleeding).5 Other causative agents include noncontracep- conditions that do not otherwise fit into the classification tive hormone therapy, drugs that interfere with sex steroid system, such as cesarean scar defects, which can cause post- hormone function or synthesis (e.g., tamoxifen), anticoagu- menstrual spotting when blood collects in the niche caused lants, and dopamine antagonists (e.g., tricyclic antidepres- by the scar. sants, some antipsychotics). Diagnostic Evaluation NOT OTHERWISE CLASSIFIED The approach to patients presenting with abnormal uterine This category contains poorly understood conditions, bleeding includes assessing for hemodynamic instability rare disorders (e.g., arteriovenous malformations), and and anemia, identifying the source of bleeding, pregnancy 438 American Family Physician www.aafp.org/afp Volume 99, Number 7 ◆ April 1, 2019  total blood loss, but quantitative assessment is impractical Yes in routine clinical practice. Historical clues such as pass- ing blood clots or changing pads/tampons at least hourly Assess hemodynamic stability suggest heavy menstrual bleeding.31 A history of postcoital bleeding may indicate cervicitis, ectropion, or, rarely, cervi- cal cancer, whereas abdominopelvic pain may suggest infec- Stable Unstable tion, structural lesions, or endometriosis. Clinicians may underestimate the prevalence of coagu- lopathies among patients with abnormal uterine bleeding.32 Continue evaluation Standard resuscitative measures These conditions should be considered in women with a family history of abnormal bleeding or a personal history Go to ! A Emergency treatment options: of heavy menstrual bleeding since menarche, or symptoms Intrauterine tamponade such as frequent bruising, bleeding gums, epistaxis, post- (temporizing measure) partum hemorrhage, or bleeding with surgical and dental Intravenous conjugated estrogen procedures.27 Dilation and curettage If severe bleeding persists: PHYSICAL EXAMINATION Uterine artery embolization An examination of the pelvis, including speculum and Hysterectomy bimanual examinations, is an important aspect of the evalu- ation of abnormal uterine bleeding. Care should be taken to Patient stabilized examine all potential bleeding sites, including the urethra, perineum, and anus. Cervical cancer screening should be If necessary, continue evaluation performed if it is not up to date. Pelvic examination can be deferred in adolescents if the patient is not sexually active, neither trauma nor infection is suspected, and the response Go to ! A to initial treatment is adequate.33 LABORATORY TESTING All patients with abnormal uterine bleeding should be evaluated for pregnancy with a urine or serum human chorionic gonadotropin test, and for anemia and thrombo- cytopenia with a complete blood count.6 Thyroid function should be evaluated in patients with signs or symptoms of thyroid disease, or if the initial workup does not reveal a likely cause.6,28,34 Additional hormonal tests (e.g., prolactin, androgens, estrogen) are indicated only if history or exam- †—Risk factors include a history of exposure to unopposed estrogen ination findings suggest a specific hormonal cause.26,28 The (Table 3), failed medical management, and persistent bleeding. ‡—Initial screening tests may be normal in the setting of some coagu- platelet count, prothrombin time, and partial thromboplas- lopathies, with diagnosis requiring further testing and possibly hema- tin time can be initial screening tests when a bleeding disor- tology consultation. der is suspected, but results may be normal in women with von Willebrand disease or other bleeding disorders. Diag- nosing a bleeding disorder typically requires additional testing, and determining whether evaluation for endome- testing, often in consultation with a hematologist.27 trial carcinoma is indicated (Figure 1).6,18,26-30 The broad Because older age is an important risk factor for endo- differential diagnosis necessitates a detailed history and metrial cancer, all patients with abnormal uterine bleeding physical examination. who are 45 years or older should undergo endometrial sam- pling.18 Younger women should undergo sampling if they BLEEDING HISTORY have a history of unopposed estrogen exposure, if medical A description of the bleeding pattern should be elicited, management fails, or if bleeding symptoms persist.6 Office- including frequency, duration, regularity, and volume. based endometrial biopsy is the preferred approach, with Heavy menstrual bleeding is defined as more than 80 mL of hysteroscopic dilation and curettage reserved for instances April 1, 2019 ◆ Volume 99, Number 7 www.aafp.org/afp American Family Physician 439  ABNORMAL UTERINE BLEEDING TABLE 4 Treatment Options for Medical Management of Abnormal Uterine Bleeding Drug Suggested dosage Notes Acute bleeding Conjugated equine estrogen Hemodynamically unstable: Follow treatment with a progestin to provoke withdrawal 25 mg intravenously every 4 to bleeding; do not use in patients at increased risk of thrombosis 6 hours for up to 24 hours Hemodynamically stable: 2.5 mg orally every 6 hours for 21 days Estrogen-progestin oral 1 monophasic pill containing Other regimens also effective; do not use in patients at contraceptives 35 mcg of ethinyl estradiol orally increased risk of thrombosis 3 times daily for 7 days Progestins Norethindrone, 5 mg orally Other high-dose oral progestins are also effective 3 times daily for 7 days Tranexamic acid 10 mg per kg intravenously every Faster onset if given intravenously; do not use in patients at 8 hours or 20 to 25 mg per kg increased risk of thrombosis orally every 8 hours Chronic bleeding Depot medroxyprogesterone 150 mg intramuscularly or Unscheduled bleeding is a common initial adverse effect, (Depo-Provera) 104 mg subcutaneously every but one-half of patients become amenorrheic after 12 months 13 weeks of use Estrogen-progestin oral 1 monophasic pill containing Other routes (transdermal patch, intravaginal ring) are likely contraceptives 35 mcg of ethinyl estradiol daily also effective; regimens with no or fewer hormone-free inter- vals may be more effective Levonorgestrel 52-mg (20-mcg-per-day) intra- Effectiveness data are based primarily on trials involving the uterine device (Mirena) 20-mcg-per-day device; effect on bleeding suppression may wane before contraceptive effectiveness expires Nonsteroidal anti-inflammatory Naproxen, 500 mg orally 2 times Other oral nonsteroidal anti-inflammatory drugs are also drugs daily effective; administer only while patient is bleeding; do not use in patients with coagulopathy Progestins Norethindrone, 2.5 to 5 mg Other oral progestins are also effective; administration during orally once daily only the luteal phase is significantly less effective for treating heavy bleeding Tranexamic acid (Lysteda) 1,000 to 1,500 mg orally 3 times Faster onset if given intravenously; do not use in patients at daily increased risk of thrombosis Note: The 2016 U.S. medical eligibility criteria for contraceptive use, published by the Centers for Disease Control and Prevention (https://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. in which office sampling fails, is inadequate, or cannot be lesions.36 Routine use of magnetic resonance imaging is performed.35 Blind sampling may miss focal lesions, so hys- discouraged but can be considered if sonographic imaging teroscopic dilation and curettage should be performed if is inadequate.6 symptoms persist despite normal biopsy results.18 Management IMAGING Multiple factors should be considered when choosing among Indications for pelvic imaging include abnormalities pal- treatment options for abnormal uterine bleeding (Table 4),37-42 pated on bimanual examination or symptoms that persist including the cause and acuity of the bleeding, fertility and despite initial treatment.6 Transvaginal ultrasonography is contraceptive preferences, medical comorbidities, adverse the first-line approach for most patients, although saline effects, cost, and relative effectiveness. If the underlying infusion sonohysterography (the infusion of sterile saline cause of bleeding can be identified and treated, symptoms into the endometrial cavity while transvaginal ultraso- may resolve without the need for additional intervention. nography is performed) is better at detecting intracavitary Anemia is an indication for treatment, as is bleeding that 440 American Family Physician www.aafp.org/afp Volume 99, Number 7 ◆ April 1, 2019  ABNORMAL UTERINE BLEEDING negatively affects the patient’s quality of life. Because exposure to unopposed SORT: KEY RECOMMENDATIONS FOR PRACTICE estrogen increases the risk of endome- trial cancer, treatment of anovulatory Evidence Clinical recommendation rating References abnormal uterine bleeding involves inducing ovulatory cycles or admin- The International Federation of Gynecology and C 5, 6 istering supplemental progesterone Obstetrics classification system should be used to char- acterize abnormal uterine bleeding. to antagonize estrogen’s proliferative effect on the endometrium. All patients with abnormal uterine bleeding should be C 6 tested for pregnancy and anemia. EMERGENT TREATMENT Endometrial biopsy should be performed in all patients C 6 Occasionally, abnormal uterine bleed- with abnormal uterine bleeding who are 45 years or ing is of sufficient quantity or duration older, in younger patients with a significant history of that emergent attention is required. unopposed estrogen exposure, persistent bleeding, or in whom medical management is ineffective. For hemodynamically unstable patients, uterine tamponade using a Transvaginal ultrasonography is the first-line imaging C 6, 36 Foley catheter or gauze packing can choice for evaluating abnormal uterine bleeding in most patients. achieve rapid but temporary control of blood loss.43 Further emergency The 20-mcg-per-day formulation of the levonorgestrel- A 44, 47 interventions for hemodynamically releasing intrauterine system (Mirena) is more effective than other medical therapies for reducing heavy men- unstable patients include intravenous strual bleeding. estrogen, dilation and curettage, uter- ine artery embolization, and, rarely, Hysterectomy is the most effective treatment for reduc- A 44, 47 hysterectomy. Medical therapy (e.g., ing heavy menstrual bleeding. oral estrogen, combined oral contra- A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality ceptives, oral progestins, intravenous patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https:// tranexamic acid) is usually adequate www.aafp.org/afpsort. for treating hemodynamically stable patients with severe bleeding. Hysterectomy is the definitive and most effective treat- NONEMERGENT TREATMENT ment for abnormal uterine bleeding, and it yields a high A wider range of medical and surgical options are available level of patient satisfaction.44,47,51 A less invasive, lower-risk for treatment of nonemergent uterine bleeding (Table 4).37-42 surgical option is endometrial ablation, which is as effec- To avoid surgical risks and preserve fertility, medical man- tive as the levonorgestrel-releasing intrauterine system.47 agement is the first-line approach for most patients.44 Among A variety of ablative techniques are available, and all are medical therapies, the 20-mcg-per-day formulation of the equivalent in terms of bleeding outcomes and patient satis- levonorgestrel-releasing intrauterine system (Mirena) is most faction.52 Myomectomy and uterine artery embolization are effective for decreasing heavy menstrual bleeding (71% to treatment options for leiomyomas, and endometrial polyps 95% reduction in blood loss) and is as effective as hysterec- can be treated with polypectomy. Except for myomectomy tomy when quality-adjusted life years are considered.39,45-47 and polypectomy, surgical interventions for abnormal uter- Estrogen-progestin oral contraceptives are effective (35% to ine bleeding are contraindicated in patients who wish to 69% reduction) and can also be used to regulate bleeding in preserve fertility. patients with ovulatory dysfunction.39,48 Continuous dosing This article updates previous articles on this topic by Sweet, et of oral progestins is another effective hormonal treatment al.53; Albers, et al.54; and Oriel and Schrager.55 option (87% reduction), but long-term patient satisfaction is low.39,49 Two effective, well-tolerated, nonhormonal choices Data Sources: A PubMed search was completed in Clinical are oral tranexamic acid (Lysteda; 26% to 54% reduction) and Queries using the key terms abnormal uterine bleeding, heavy menstrual bleeding, irregular menstrual bleeding, menorrhagia, nonsteroidal anti-inflammatory drugs (10% to 52% reduc- metrorrhagia, and dysfunctional uterine bleeding. The search tion).39,50 Both are taken only when the patient is bleeding, included meta-analyses, randomized controlled trials, clinical and tranexamic acid has the added benefit of being safe while trials, and reviews. Also searched were the Agency for Health- the patient is attempting to conceive. care Research and Quality evidence reports, Clinical Evidence, April 1, 2019 ◆ Volume 99, Number 7 www.aafp.org/afp American Family Physician 441  ABNORMAL UTERINE BLEEDING the Cochrane database, and UpToDate. Search dates: August 21, 14. Baiocchi G, Manci N, Pazzaglia M, et al. Malignancy in endometrial 2017, and November 10, 2018. polyps: a 12-year experience. Am J Obstet Gynecol. 2009;201(5): 462.e1-462.e4. 15. Taran FA, Stewart EA, Brucker S. Adenomyosis: epidemiology, risk fac- The Authors tors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd. 2013;73(9):924-931. NOAH WOUK, MD, is a family medicine physician at Piedmont 16. 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April 1, 2019 ◆ Volume 99, Number 7 www.aafp.org/afp American Family Physician 443  BONUS DIGITAL CONTENT ABNORMAL UTERINE BLEEDING eTABLE 2 Differential Diagnosis of Abnormal Uterine Bleeding Uterine bleeding Coagulopathies Ovulatory dysfunction Pregnancy Factor deficiencies Androgen excess Abortion Platelet dysfunction Androgen insensitivity syndrome Abruption Thrombocytopenia Hormone-producing tumors Ectopic pregnancy von Willebrand disease Polycystic ovary syndrome Gestational trophoblastic Iatrogenic Hypothalamic-pituitary-adrenal axis disease Anticoagulants dysfunction Subchorionic hemorrhage Antidepressants Congenital adrenal hyperplasia Structural Antipsychotics Cushing syndrome/disease Adenomyosis Chemotherapeutic agents Hyperprolactinemia Arteriovenous malformations Copper intrauterine device Immature hypothalamic-pituitary- Cesarean scar defect adrenal axis (adolescence) Endometriosis Corticosteroids Intense exercise, stress Leiomyomas Hormonal contraception or other hormone therapy Lactational amenorrhea Malignancy Phenytoin (Dilantin) Ovarian follicle decline (perimenopause) Endometrial hyperplasia/ Tamoxifen Starvation (including eating disorders) carcinoma Infection Thyroid disorders Metastasis Acute or chronic endometritis Tumors, radiation, or trauma of the Uterine sarcoma pituitary/hypothalamus area Outflow obstruction Pelvic inflammatory disease Premature ovarian failure Polyp Nonuterine bleeding Adnexa Cervix Vagina Other Malignancy Dysplasia/malignancy Atrophy Chronic kidney disease Pelvic inflammatory disease Ectropion Benign growths Chronic liver disease Anus Endometritis Infection Diabetes mellitus Anal fissure Infection (e.g., gonor- Malignancy Leukemia Hemorrhoids rhea, chlamydia) Retained foreign body Sarcoidosis of the Inflammatory bowel disease Polyps Trauma reproductive tract Upper or lower gastro- Urethra Ulcerative conditions Tuberculosis of the intestinal bleeding Urethral diverticula reproductive tract Vulva Bladder/ureters/kidneys Urethral prolapse Turner syndrome Benign growths Infection Urethritis Blistering diseases Malignancy Malignancy Nephrolithiasis Trauma Information from references 9 through 11. April 1, 2019 ◆ Volume 99, Number 7 www.aafp.org/afp American Family Physician 443A