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Abnormal Uterine Bleeding Bophal Sarha Hang INTRODUCTION Abnormal uterine bleeding is an overarching term that is defined as bleeding from the uterine corpus that is irregular in volume, frequency, or duration in absence of pregnancy ( Table 96-1). 1,2 Vaginal bleeding is a common complaint in the ED, and differential diagnoses include preg nancy, structural abnormalities (e.g., polyps, fibroids), endometritis, coagulopathies, trauma, and various other causes. This chapter will focus on the ED evaluation and management of abnormal uterine bleeding. MENSTRUAL CYCLE A normal menstrual cycle has an average duration of 4.5 to 8 days and an interval of 24 to 38 days between the onset of menses. The average blood loss is ≤30 mL, and menstrual blood loss >80 mL is considered abnormal. Menstrual cycle variation during early menarche and the perimenopausal period is due to high prevalence of anovulation. Figure 96-1 depicts hormonal and endometrial changes associated with a normal menstrual cycle. In response to the rising estrogen levels, the pituitary gland secretes follicle-stimulating hormone and luteinizing hormone, stimulating the release of a mature oocyte. The residual follicular capsule forms the corpus luteum. During the luteal phase, the corpus luteum secretes estrogen and progesterone, which maintains the integrity of the endometrium for implantation. In the absence of human chorionic gonadotropin released by a pregnancy, the corpus luteum involutes, and estrogen and proges terone levels fall. Hormonal withdrawal causes vasoconstriction in the spiral arterioles of the endometrium, resulting in endometrial sloughing and leading to menses. CLINICAL FEATURES  HISTORY Obtaining a focused medical history should include bleeding pattern, associated symptoms, and past medical, reproductive, and sexual history ( Table 96-2). The average tampon or pad absorbs 20 to 30 mL of vaginal effluent. However, judging the amount of blood loss by usage may be unreliable because personal habits vary greatly among women. In women with heavy bleeding, there may be insufficient time for fibri nolysis, so blood clots form. Determine whether bleeding is acute or chronic. It is also important to elicit whether there is a family history of bleeding disorders or chronic illnesses. Up to 20% of women with heavy bleeding have an underlying coagulation disorder, with von Willebrand’s disease being the most common. Screening criteria include heavy menstrual bleeding since menarche, postpartum hemorrhage, bleeding related to surgery or dental procedure, and two or more of the following: bruising one to two times a month, epistaxis one to two times a month, frequent gum bleeding, or family history. Medications, such as hormonal contracep tives, anticoagulants, selective serotonin reuptake inhibitors, tamoxifen, and herbal supplements (e.g., ginseng), are also important causes of bleeding.  PHYSICAL EXAMINATION Evaluate for hemodynamic stability on initial assessment. Significant signs of volume depletion may not be present until bleeding is profuse. A focused physical examination including pelvic is required to exclude life-threatening blood loss and need for emergent surgical intervention. Hirsutism, obesity, and galactorrhea may point toward endocrinologic causes. Petechiae, purpura, and mucosal bleeding require further hematologic investigation. For pelvic examinations in the ED, both male and female physicians are equally advised to have a chaperone present.

nd need for emergent surgical intervention. Hirsutism, obesity, and galactorrhea may point toward endocrinologic causes. Petechiae, purpura, and mucosal bleeding require further hematologic investigation. For pelvic examinations in the ED, both male and female physicians are equally advised to have a chaperone present. Inspect the perineum, vulva, urethra, and perianal region before speculum exam. Evaluate the vaginal canal and cervix for potential causes of bleeding. Bimanual exam of the uterus and adnexal structures should be performed to assess for size, masses, or tenderness. In elderly patients, immobility and degenerative joint disease may make it difficult to place the patient in the dorsal lithotomy position. Patients may be positioned supine, with the head supported with a pil low and with knees flexed and hips externally rotated (frog-leg position). Consider using a smaller speculum with generous lubrication if there is vaginal atrophy. Abnormalities such as irregular nodules, masses, or thickened rectovaginal septum may suggest malignancy. CAUSES OF VAGINAL BLEEDING The causes of abnormal uterine bleeding are classified into structural and nonstructural causes, using the acronym PALM-COEIN: Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia, Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, and Not otherwise classified. 4 Causes of bleeding based on age are shown in Table 96-3. The term abnormal uterine bleeding encompasses all causes of abnormal bleeding in nonpregnant women, and the most likely causes are largely determined by patient age. Because the first clinical signs of heavy menstrual bleeding (heavy uterine bleeding) are noted after the onset of menses during early adolescence, structural causes are uncommon. Anovulatory and bleeding disorders are most common during this time period (ages 13 to 19). Pregnancy-related complications become the most common cause of abnormal vaginal bleeding during the reproductive years. Issues regarding pregnancy are covered in Chapters 98, “Ectopic Pregnancy and Emergencies in the First 20 Weeks of Pregnancy, ” and 100, “Maternal Emergencies After 20 Weeks of Pregnancy and in the Peripartum Period. ” Abnormal uterine bleeding as a result of local structural pathology such as polyps and fibroids is not typically seen until women reach their mid-30s. Perimenopausal anovulatory bleeding is typically seen in the mid to late 40s. Postmenopausal bleeding is often related to atrophic vaginitis, exogenous hormones, and malignancy. STRUCTURAL CAUSES OF VAGINAL BLEEDING  POLYPS Endometrial and endocervical polyps are epithelial proliferations that most often are benign. Although most polyps are asymptomatic, polyps can be a cause of abnormal uterine bleeding in women older than 35 years. A common symptom is intermenstrual bleeding, and diagnosis is made on US or hysteroscopy. Obstetrics and Gynecology SECTION CHAPTER Tintinalli_Sec11_p0607-0668.indd 607 8/2/19 4:20 PM

ften are benign. Although most polyps are asymptomatic, polyps can be a cause of abnormal uterine bleeding in women older than 35 years. A common symptom is intermenstrual bleeding, and diagnosis is made on US or hysteroscopy. Obstetrics and Gynecology SECTION CHAPTER Tintinalli_Sec11_p0607-0668.indd 607 8/2/19 4:20 PM 608 SECTION 11: Obstetrics and Gynecology TABLE 96-1 FIGO Terminology for Bleeding2* Type Definition Abnormal uterine bleeding Bleeding that is abnormal in regularity, volume, frequency, or duration. Bleeding may be acute or chronic and is present for at least 6 months. Heavy menstrual bleeding (heavy uterine bleeding [HUB] replaces menorrhagia) Excessive menstrual bleeding that interferes with a woman’s physical, emotional, social, and quality of life. Note that the definition is menstrual bleeding deemed excessive by the patient regardless of duration, frequency, or timing. Amenorrhea Bleeding that is absent for >6 months. Prolonged menstrual bleeding Menstrual periods that exceed 8 days’ duration on a regular basis. Intermenstrual bleeding (replaces metrorrhagia) Bleeding episodes between normally timed menstrual periods. Irregular menstrual bleeding Unpredictable onset of menses, with cycle variations >20 days over a period of 1 year. Postmenopausal bleeding Any bleeding that occurs >12 months after cessation of menstruation. Abbreviation: FIGO = International Federation of Gynecology and Obstetrics. Source: https://www.figo.org/news/ground-breaking-figo-classification-published-ijgo-0014139. *Discarded terms include dysfunctional uterine bleeding, menorrhagia, functional uterine bleeding, hypermenorrhea, hypomenorrhea, menometrorrhagia, metrorrhagia, oligomenorrhea, polymenorrhea, and uterine hemorrhage.2 Endocrine cycle Ovarian histology Endometrial histology Body temperature (°C) 37 .0 36.5 36.0 02468 10 12 14 16 18 20 22 24 26 28 Follicular phase Luteal phase E2 FSH Dominant follicle Menses Ovulation Follicular recruitment Corpus luteum Days FIGURE 96-1. The hormonal, ovarian, endometrial, and basal body temperature changes and relationships throughout the normal menstrual cycle. E 2 = prostaglandin E2; FSH = folliclestimulating hormone; LH = luteinizing hormone; P = progesterone. [Reproduced with permission from Patel DR, Greydanus DE, Baker RJ: Pediatric Practice Sports Medicine. © 2009, McGraw-Hill, Inc., New York, NY.]  ADENOMYOSIS Adenomyosis is the presence of endometrial glands and stroma within the myometrium. The histopathology is often diffuse within the uterus, but localized areas of growth are called adenomyomas. Symptoms include painful, heavy periods most commonly seen in the fourth and fifth decade of life. MRI is the imaging modality of choice, but US is a good alternative. Patients with severe bleeding unresponsive to medical management often require surgical management.  LEIOMYOMAS Uterine fibroids (also called leiomyoma or myoma) are the most com mon benign tumors of the pelvis in women; an estimated 25% of white women and 50% of black women have fibroids in their reproductive years. The cause is unclear, but fibroids increase with reproductive age and decrease in size during menopause. Thus, growth is thought to be dependent on genetic and hormonal factors. In some cases, fibroids may enlarge early in pregnancy and with oral contraceptive pill use. Most fibroids are asymptomatic, but up to 30% of patients with leio myomas experience pelvic pain and abnormal bleeding. Acute pain is rare, but severe pain may be experienced with torsion or degeneration. Degeneration results from rapid growth and loss of blood supply, often seen during early pregnancy. A rare case of spontaneous fibroid rupture causing massive intra-abdominal hemorrhage has been reported in the literature.

al bleeding. Acute pain is rare, but severe pain may be experienced with torsion or degeneration. Degeneration results from rapid growth and loss of blood supply, often seen during early pregnancy. A rare case of spontaneous fibroid rupture causing massive intra-abdominal hemorrhage has been reported in the literature. Signs and symptoms of fibroids vary depending on size and location. Large fibroids may be palpated on abdominal or rectal exam. Symptoms Tintinalli_Sec11_p0607-0668.indd 608 8/2/19 4:20 PM

al bleeding. Acute pain is rare, but severe pain may be experienced with torsion or degeneration. Degeneration results from rapid growth and loss of blood supply, often seen during early pregnancy. A rare case of spontaneous fibroid rupture causing massive intra-abdominal hemorrhage has been reported in the literature. Signs and symptoms of fibroids vary depending on size and location. Large fibroids may be palpated on abdominal or rectal exam. Symptoms Tintinalli_Sec11_p0607-0668.indd 608 8/2/19 4:20 PM CHAPTER 96: Abnormal Uterine Bleeding 609 of acute degeneration include tenderness, rebound guarding, fever, and elevated WBC count. Rapid growth at any age or growth after meno pause is highly suspicious for malignant transformation. The best diag nostic test is ultrasonography, which is as sensitive as MRI. In the ED, management is focused on treating complications associ ated with fibroids. Iron deficiency anemia is often long-standing and may require a blood transfusion. Other complications are rarer, but constipation, urinary retention, vaginal or intraperitoneal hemorrhage, TABLE 96-2 Important Historical Elements in Uterine Bleeding Category Details Reproductive history Age of menarche Menstrual history Date of the last menstrual period Pattern of normal and abnormal bleeding or discharge Presence of dysmenorrhea Sexual history Current sexual activity Contraception Use of barrier protection Pregnant—yes/no? Gravida and para Previous abortion or recent termination History of ectopic pregnancy History of pelvic inflammatory disease, sexually transmitted diseases, human immunodeficiency virus, and hepatitis status History of trauma Postcoital bleeding Possibility of retained foreign body — Medications, including alternative and complementary medicine Anticoagulants NSAIDs Ginseng Past medical history Signs and symptoms of coagulopathy, including nosebleeds, petechiae, and ecchymoses Endocrine disorders, including diabetes, pituitary tumors, polycystic ovary disease, hyperthyroidism, and hypothyroidism Liver disease Associated symptoms Urinary, GI, musculoskeletal symptoms; fever or syncope TABLE 96-3 Causes of Bleeding by Age Group* Adolescent Reproductive Perimenopausal Postmenopausal Anovulation (hypothalamicpituitary-ovarian immaturity) Pregnancy Anovulation Atrophic vaginitis (30%) Pregnancy Anovulation (PCOS) Uterine leiomyomas Exogenous hormone use (30%) Exogenous hormones or OCP Exogenous hormone use or OCP Cervical and endometrial polyps Endometrial lesions, including cancer (30%) Coagulopathy Uterine leiomyomas Thyroid dysfunction Other tumor—vulvar, vaginal, cervical (10%) Pelvic infections Cervical and endometrial polyps

rine leiomyomas Exogenous hormone use (30%) Exogenous hormones or OCP Exogenous hormone use or OCP Cervical and endometrial polyps Endometrial lesions, including cancer (30%) Coagulopathy Uterine leiomyomas Thyroid dysfunction Other tumor—vulvar, vaginal, cervical (10%) Pelvic infections Cervical and endometrial polyps Thyroid dysfunction Abbreviations: OCP = oral contraceptive pill; PCOS = polycystic ovary syndrome. *Prepubertal bleeding is discussed in Chapter 136, “Pediatric Urologic and Gynecologic Disorders.” deep vein thrombosis, and mesenteric thrombosis have been reported. 6 NSAIDs are the mainstays for analgesia in the ED. Medical management with hormonal agents may be initiated in the ED with gynecologic consultation. Tranexamic acid can reduce menstrual blood loss from uterine fibroids. 7 See discussion below on tranexamic acid. Surgical removal of fibroids is associated with a 25% to 30% rate of recurrence and significant bleeding complications. Uterine artery embolization is an effective treatment for symptomatic fibroids, resulting in decreased fibroid volume and alleviation of symptoms.  MALIGNANCY Any malignancy of the genital tract, in particular endometrial or cervical cancer, may produce bleeding. Consider endometrial hyperplasia or cancer in women >45 years old or in younger women with other risk factors. 9 The amount of bleeding does not correlate with the severity of disease. All patients with postmenopausal bleeding warrant prompt outpatient referral for US and endometrial biopsy. Elderly patients may not be able to accurately describe the location of pain or bleeding in the proximity of the bladder, uterus, or rectum. Therefore, make sure to adequately visualize the urethra, vagina, and cervix on pelvic examination. Vaginal bleeding, especially when seen in conjunction with atrophic vaginitis, may be associated with the use of pessaries and douche solu tions, which can irritate the mucosa. Cervical polyps can also cause vaginal bleeding. However, an endometrial biopsy is ultimately required to rule out other serious causes of bleeding. NONSTRUCTURAL CAUSES OF VAGINAL BLEEDING  COAGULOPATHIES Primary coagulation disorders account for up to 20% of acute uterine bleeding in adolescents. 10 von Willebrand’s disease is the most common cause, but myeloproliferative disorders and immune thrombocytopenia also may be diagnosed. In adults, bleeding may result from anticoagulation agents or acquired bleeding disorders. Cirrhosis may lead to bleeding secondary to reduced capacity of the liver to metabolize estrogens.  OVULATORY DYSFUNCTION Acute uterine bleeding secondary to anovulation is seen in 10% to 15% of gynecologic patients. Signs include irregular and/or heavy menstruation. Ovulatory dysfunction is common in perimenarchal and perimenopausal women, as well as in patients with endocrine disorders, polycystic ovary syndrome, exogenous hormone use, and liver or renal disease. Anovulatory uterine bleeding in adolescence is due to the immature hypothalamic-pituitary-ovarian axis. In this situation, the amount of bleeding is usually minimal and painless. Severe anemia from heavy menstrual bleeding in early adolescence should prompt evaluation for bleeding disorders (e.g., von Willebrand’s disease, factor VIII defi ciency). Table 96-4 outlines the medical management of acute uterine bleeding from ovulatory dysfunction in the ED. Anovulatory bleeding in the reproductive-age female may be regular in timing, but more often is irregular because of fluctuating estrogen levels. Characteristically, anovulatory cycles present as prolonged amenor rhea with periodic heavy menstrual bleeding. This pattern of bleeding increases the risk of endometrial hyperplasia and adenocarcinoma.

reproductive-age female may be regular in timing, but more often is irregular because of fluctuating estrogen levels. Characteristically, anovulatory cycles present as prolonged amenor rhea with periodic heavy menstrual bleeding. This pattern of bleeding increases the risk of endometrial hyperplasia and adenocarcinoma. Hypothyroidism may be associated with heavy uterine bleeding or intermenstrual bleeding from ovulatory dysfunction, with an estimated incidence of 0.3% to 2.5%. 11 Eating disorders, excessive weight loss, stress, and exercise can also cause abnormal uterine bleeding. Consider obtaining thyroid-stimulating hormone levels in women with uterine bleeding of undetermined origin or in those with thyroid nodule or goiter.  ENDOMETRIAL CAUSES Abnormal uterine bleeding that occurs in the context of normal ovulation and with a structurally normal endometrial cavity is attributed to endometrial causes. Normal ovulation is based on a history of regular men strual periods. Bleeding may be preceded by breast tenderness, abdominal Tintinalli_Sec11_p0607-0668.indd 609 8/2/19 4:20 PM

leeding that occurs in the context of normal ovulation and with a structurally normal endometrial cavity is attributed to endometrial causes. Normal ovulation is based on a history of regular men strual periods. Bleeding may be preceded by breast tenderness, abdominal Tintinalli_Sec11_p0607-0668.indd 609 8/2/19 4:20 PM 610 SECTION 11: Obstetrics and Gynecology  OTHER CAUSES OF VAGINAL BLEEDING Pelvic inflammatory disease or infections that cause endometritis can result in abnormal vaginal bleeding. Cervical erosions, polyps, and cer vicitis may cause bleeding from the cervix. Vaginal infections, trauma, and foreign bodies may also present with abnormal bleeding. Emer gency therapy should be directed at investigating and treating obvious causes of bleeding. For further details, see Chapters 103, “Pelvic Inflammatory Disease, ” and 102, “Vulvovaginitis. ” LABORATORY EVALUATION AND IMAGING Obtain a pregnancy test in women of childbearing age (except those with hysterectomy) to rule out pregnancy as a cause of bleeding. A CBC identifies anemia. Consider thyroid studies if they have not been recently obtained. Obtain coagulation studies only when indicated by history or physical examination. In individuals with suspected endo crine disorders, determination of prolactin levels may be helpful, but the levels may not be available for ED evaluation. Ultrasonography is the first-line imaging modality for gynecologic conditions such as vaginal bleeding, adnexal or uterine masses, or pelvic pain. US can determine uterine size and endometrial characteristics and can identify the presence of leiomyoma, ovarian cysts, hydrosalpinx, pelvic adhesions, tubo-ovarian abscesses, endometriosis, and tumors. Transvaginal ultrasonography further delineates ovarian cysts and fluid in the cul-de-sac. Depending on the degree of pain and findings on physical examination, US can be done on an emergency basis or deferred for outpatient evaluation. CT is used primarily in the ED for the evaluation of acute abdominal or pelvic pain (see Chapter 97, “ Abdominal and Pelvic Pain in the Nonpregnant Female”). MRI is used primarily for cancer staging and is rarely indicated during ED evaluation. bloating, and pelvic pain. The diagnosis is made when patients have heavy menstrual bleeding with no other identifiable abnormalities. Ovulatory dysfunction bleeding is generally treated with oral contra ceptives, NSAIDs, or progestins ( Table 96-4). NSAIDs reduce prosta glandin levels and can reduce menstrual bleeding. Endometrial ablation may be useful for those who do not respond to medical therapy; hys terectomy is reserved for those who fail medical management and have excessive blood loss.  IATROGENIC CAUSES Oral contraceptive pill use remains the most common cause of intermenstrual bleeding. Additionally, medications (e.g., antiseizure medications) that increase the P450 system of the liver may increase the metabolism of endogenous hormonal glucocorticoids and may cause withdrawal bleeding. Hormone replacement therapy, which can relieve symptoms associ ated with menopause, may also be associated with vaginal bleeding. Hormone replacement therapy for symptom control has been called into question, as there is no clear benefit for primary and secondary prevention of cardiovascular disease, and excessive risk of endometrial, breast, and colorectal cancer and thromboembolism has been noted. 12,13 Forty percent of women receiving continuous oral contraceptive pill therapy will experience abnormal bleeding in the initial 4 to 6 months. Bleeding after 6 months of continuous combined hormone replacement therapy, unexpected bleeding with cyclic hormone replacement therapy, or bleeding that recurs after amenorrhea is established should prompt referral for evaluation.

ntraceptive pill therapy will experience abnormal bleeding in the initial 4 to 6 months. Bleeding after 6 months of continuous combined hormone replacement therapy, unexpected bleeding with cyclic hormone replacement therapy, or bleeding that recurs after amenorrhea is established should prompt referral for evaluation. There are no acceptable criteria for “abnormal bleeding” on these therapies. The most common etiologies for bleed ing while on hormone replacement therapy are poor compliance, poor GI absorption, drug interactions, failure to synchronize therapy with endogenous ovarian activity, and coagulation disorders. TABLE 96-4 Treatment of Massive or Heavy Vaginal Bleeding Massive or Life-Threatening Bleeding General management Fluid and blood resuscitation Identify and treat coagulopathies Exclude pregnancy, foreign body, laceration

tions, failure to synchronize therapy with endogenous ovarian activity, and coagulation disorders. TABLE 96-4 Treatment of Massive or Heavy Vaginal Bleeding Massive or Life-Threatening Bleeding General management Fluid and blood resuscitation Identify and treat coagulopathies Exclude pregnancy, foreign body, laceration Initial Dose Dose Schedule Comments Contraindications Conjugated equine estrogen (Premarin) 25 milligrams IV Every 4–6 hours until bleeding diminishes/stops Emergency GYN consultation; provide antiemetics If VTE, thrombophilia, vascular disease, or malignancy, do not give estrogens and get emergency GYN consultation Tranexamic acid (FDA approved for menorrhagia) 1.0–1.3 grams IV Can continue PO 3 times a day; effective in about 3 h Emergency GYN consultation If VTE, thrombophilia, vascular disease, or malignancy, do not give tranexamic acid and get emergency GYN consultation Hemodynamically Stable or Ovulatory Dysfunction Dose Dose Schedule Comments Contraindications Combined OCP (i.e., Sprintec ® ): 0.25 milligram norgestimate and 0.035 milligram ethinyl estradiol; Yaz ® , Alesse® , Seasonale® , other options with a bit less estrogen) Monophasic combined OCP that contains ≤35 micrograms of ethinyl estradiol Three times a day for 7 days Twice daily for 5 days, then once daily until pack is finished Provide antiemetics; bleeding diminishes/stops in ~3 days Smokers >35 years, hypertension, pregnancy, VTE, cerebrovascular accident, breast cancer, liver disease, thromboembolic disorders, diabetes with vascular disease, heart disease, major surgery with immobilization Medroxyprogesterone acetate 20 milligrams PO 3 times a day for 7 days Once daily for 10 days Bleeding diminishes/stops in ~3 days; for patients with contraindications to estrogen; primarily for older or perimenopausal patients Liver disease; breast, uterine, or ovarian cancer; inconsistent reports of deep venous thrombosis risk NSAIDs Naproxen or ibuprofen PO or mefenamic acid Naproxen 500 milligrams twice a day; ibuprofen 400 milligrams every 6 hours; mefenamic acid, 500 milligrams 3 times daily for 4–5 days or until bleeding stops Consider for younger patients with relatively stable bleeding and those who cannot receive hormonal therapy Use NSAIDS with caution in patients with history of GI bleed, bleeding disorders, or renal disease Abbreviations: FDA = U.S. Food and Drug Administration; GYN = gynecology; OCP = oral contraceptive pill; VTE = venous thromboembolism. Tintinalli_Sec11_p0607-0668.indd 610 8/2/19 4:20 PM

ho cannot receive hormonal therapy Use NSAIDS with caution in patients with history of GI bleed, bleeding disorders, or renal disease Abbreviations: FDA = U.S. Food and Drug Administration; GYN = gynecology; OCP = oral contraceptive pill; VTE = venous thromboembolism. Tintinalli_Sec11_p0607-0668.indd 610 8/2/19 4:20 PM CHAPTER 96: Abnormal Uterine Bleeding 611 TREATMENT  MASSIVE UTERINE BLEEDING Women who are hemodynamically unstable need immediate resus citation and emergent gynecologic consultation ( Table 96-4). Do not attempt vaginal packing, because it increases the risk of infection and may hide ongoing blood loss. In addition to fluid resuscitation, blood transfusion, and identification and correction of underlying coagu lopathies, assess for other potential causes of bleeding including trauma, bleeding dyscrasia, infection, and retained foreign bodies. The options for management of acute hemorrhage include hormonal, surgical, and hemostatic interventions. Hormonal agents are first-line medical management for massive uterine bleeding in patients without an underlying bleeding disorder. Short-term hormonal treatment allows the endometrium to stabilize and slows acute bleeding. For severe hemorrhage, give conjugated estrogen (Premarin ® ) at a dose of 25 milligrams IV every 4 to 6 hours until bleeding stops, with further treatment and disposition determined by the gynecologist. In women with a history of blood clot or cardiovas cular disease, high-dose estrogen therapy is contraindicated, so obtain emergency gynecologic consultation for other treatment options. Obtain transvaginal US to identify anatomic causes of bleeding. Tranexamic acid, a lysine derivative that prevents fibrin degradation, has been primarily used for intraoperative gynecologic and obstetric hemorrhage. 15,16 Obtain gynecologic consultation if IV administration is considered, especially to discuss the risks and benefits. Clinical studies on the effectiveness of tranexamic acid have excluded patients with the potential for thrombosis. However, the U.S. Food and Drug Admin istration has approved PO tranexamic acid for treatment of ovulatory abnormal uterine bleeding. A recent review showed no thromboembolic events with the use of PO regimens. The most commonly recommended and studied treatment regimen is PO tranexamic acid 1 to 1.3 grams every 6 to 8 hours for 5 days.  HEAVY OR ANOVULATORY MENSTRUAL BLEEDING The most common medication treatment options for heavy menstrual bleeding (Table 96-4) include hormonal (i.e., combined contraceptives, progestin-only) and nonhormonal therapies (i.e., NSAIDs). Common side effects include nausea and vomiting. Simplified ED regimens for combined oral contraceptive pills and progestin-only pills are outlined in Table 96-4. The median time to stop bleeding for either regimen (combined oral contraceptive pill or progestin-only regimen) is 3 days. However, multiple different hormonal doses and schedules are also effective. In general, for young healthy women in whom bleeding is often related to anovulation and there is no concern for endometrial pathology, oral contraceptive pills are favored. For older patients or obese/perimenopausal patients in whom there could be concern for endometrial pathology, progestin-only therapy is preferred. Oral contraceptive pills have long been an excellent choice for ado lescents and women requiring contraception. Heavy menstrual bleeding is decreased by 50%, with a similar reduction in the degree of pain associated with bleeding. Alternative therapy at gynecologic follow-up can consist of a levonorgestrel intrauterine device (71% to 95% reduction), which may be superior to combined oral contraceptive pills (35% to 69% reduction) and NSAIDs (10% to 52% reduction).

d by 50%, with a similar reduction in the degree of pain associated with bleeding. Alternative therapy at gynecologic follow-up can consist of a levonorgestrel intrauterine device (71% to 95% reduction), which may be superior to combined oral contraceptive pills (35% to 69% reduction) and NSAIDs (10% to 52% reduction). NSAIDs are effective in reducing pain and blood loss in 20% to 50% of women with abnormal uterine bleeding secondary to ovulatory dysfunction. 19 NSAIDs should be started on the first day of the period and continued until bleeding stops and pain resolves. All NSAIDs inhibit cyclooxygenase in the arachidonic acid cascade. Prostaglandin inhibitors alter the ratio of prostaglandin F 2α, which causes vasoconstriction, to prostaglandin E2, which causes vasodilation. NSAIDs also increase levels of thromboxane A2, which causes vasoconstriction and increases platelet aggregation. NSAIDs have a mild side effect profile and are inexpensive. Treatment choices include mefenamic acid, 500 milligrams three times a day PO, naproxen, 500 milligrams twice per day PO, and ibuprofen, 400 milligrams every 6 hours. Any of these may be administered to reduce bleeding and pain associated with use of an intrauterine device. 18 NSAIDs are less useful in patients with uterine leiomyomas. For women with contraindications to estrogen, progestin-only therapy is an alternative therapy. Progestin works by decreasing the number of available estrogen receptors and stabilizing the endometrium. Progestin is used when there is concern for underlying endometrial pathology or hyperplasia. The American College of Obstetricians and Gynecologists recommends medroxyprogesterone acetate, 20 milligrams three times per day for 7 days. Another common regimen is medroxyprogesterone acetate, 10 milligrams daily PO for 10 days. Gonadotropin-releasing hormone agonists may be used to induce amenorrhea, but women on this therapy become menopausal. Other drawbacks include medication expense and bone loss when used for >6 months. Oral tranexamic acid, a fibrinolytic, reduces vaginal bleeding with minimal side effects. An improved quality of life in patients using tranexamic acid when compared with hormone therapy and NSAIDs has been reported. Nonmedical invasive management strategies may be required if medical treatment fails. These include hysteroscopy, endometrial ablation, or myomectomy. Hysteroscopy can be used to sample the endometrium and resect polyps and myoma. Endometrial ablation may be performed in patients who do not desire fertility, have no pathologic diagnosis, and for whom medical therapy has failed. 21 Myomectomy may be useful in patients with symptomatic fibroids. Hysterectomy is reserved for selected patient populations. Uterine artery embolization is an effective nonsurgical option for the management of bleeding caused by fibroids. DISPOSITION AND FOLLOW-UP Stable patients can be discharged home with arrangements for prompt follow-up. The need for surgical management is based on clinical stability. If medical management fails or if there is a contraindication (e.g., thromboembolic disease), then surgical management is the next step. Surgical options are directed by suspected etiology and include dilatation and curettage, hysteroscopy, endometrial balloon tamponade, and uterine artery embolization. Hysterectomy is used as a last resort in patients with acute life-threatening bleeding unresponsive to other treatment measures. Provide referral for endometrial biopsy for patients at risk for endo metrial cancer and all women >45 years old. Perimenopausal bleeding is associated with malignancy in 10% of women. Risk factors include obesity, nulliparity, history of anovulation, tamoxifen use, infertility, and a family history of endometrial or colon cancer.

rral for endometrial biopsy for patients at risk for endo metrial cancer and all women >45 years old. Perimenopausal bleeding is associated with malignancy in 10% of women. Risk factors include obesity, nulliparity, history of anovulation, tamoxifen use, infertility, and a family history of endometrial or colon cancer. Other diagnostic procedures performed at follow-up may include sonohysterography, hysterosalpingography, and hysteroscopy with directed biopsy and dilatation and curettage. SPECIAL CONSIDERATIONS  ANTICOAGULANTS Anticoagulation for deep vein thrombosis, pulmonary embolism, artificial heart valves, atrial fibrillation, and other conditions may be a cause of abnormal uterine bleeding. More than 70% of these women report changes in their periods, with more than half reporting heavy menstrual bleeding. 24 The management of women with active or prior thrombotic disease is challenging because first-line treatments such as combined contraceptives and tranexamic acid are contraindicated in this popula tion. Progestin-only may be used with caution and gynecologic consul tation due to potential increased risk of thrombosis. Risks and benefits must be evaluated for reversal of anticoagulation.  INHERITED BLEEDING DISORDERS Abnormal uterine bleeding is the most common symptom of inherited bleeding disorders in women. Of historical interest, the first described case of von Willebrand’s disease was in a 13-year-old who died as a result of uncontrollable uterine bleeding. 25 Abnormal uterine bleeding is present in the majority of women with von Willebrand’s disease or factor XI deficiency and in carriers of hemophilia. Tintinalli_Sec11_p0607-0668.indd 611 8/2/19 4:20 PM