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Definition and Epidemiology
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The normal menstrual cycle consists of the follicular (or proliferative) phase, the ovulation phase, and the luteal (or secretory) phase. During the first 5 days of the follicular phase menstruation occurs secondary to the disintegration and sloughing of the functionalis layer of the endometrium. From day 5 to day 14, this phase is characterized by endometrial proliferation caused by estrogen produced by the ovarian follicle under the influence of follicle stimulating hormone (FSH). This period ends as estrogen production peaks. This triggers the FSH and luteinizing hormone (LH) surge. After 24 to 36 hours of the LH surge, the ovarian follicle ruptures releasing the ovum. This process is known as the ovulation phase. From day 15 to 28, the luteal phase occurs, which is characterized by the proliferation of progesterone and estrogen by the corpus luteum (formed by luteinization of the follicular cells). Here the endometrium increases in thickness, and the stroma becomes edematous. If pregnancy does not occur, the corpus luteum will regress, and estrogen and progesterone levels will decrease. This feedback will cause an increase in FSH and LH, initiating the next cycle (Fig. 101-1).36–38
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In a normal menstrual cycle, menstruation occurs every 24 to 38 days, lasts from 4.5 to 8 days, and produces an average of 5 to 80 mL of blood loss. AUB, formerly called dysfunctional uterine bleeding, is a diagnosis of exclusion and is defined in terms of disturbances of regularity, of frequency, and of duration, or volume of menstrual flow that occurs only when organic and structural causes for abnormal vaginal bleeding have been ruled out (Table 101-5).39,40
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AUB accounts for 20% of all gynecologic visits. Of these, 20% are adolescents and 50% are women aged 40 to 50 years. Furthermore, a reported 25% of gynecologic surgeries involve AUB.41,42
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Approximately 90% of AUB results from anovulation, with adolescent and perimenopausal women being the most affected. In adolescents, specifically during the first 2 years post menarche, anovulatory estrogen breakthrough bleeding is common secondary to immaturity of the hypothalamic–ovarian axis. The LH surge is unable to respond to rising estradiol levels causing failure to induce ovulation. As a result, the corpus luteum is not formed, and the progesterone level remains low or absent, allowing the endometrium to proliferate under the influence of unopposed estrogen. Ultimately, the endometrium outgrows the blood supply and architectural support, resulting in menometrorrhagia.37,43–45
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In perimenopausal women, anovulatory estrogen withdrawal bleeding occurs secondary to a shortened follicular phase. The ovarian follicles secrete less estradiol leading to insufficient endometrial proliferation with irregular and light menstrual bleeding. This also occurs in prepubertal girls.37,43,44,46,47
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Approximately 10% of AUB occurs in women of reproductive age (15–35 years) who have normal ovulatory cycles. This is characterized by regular menses but heavy menstrual loss. There is no disturbance of pituitary–ovarian axis and the hormonal profile is normal.43
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Etiology/Risk Factors
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The most common cause of anovulatory AUB is polycystic ovary syndrome (PCOS), which affects approximately 6% of women of reproductive age.48 Patients with polycystic ovary syndrome (PCOS) may experience heavy bleeding with very long or short cycles. PCOS is often associated with type 2 diabetes, overweight, insulin resistance, hirsutism, acanthosis nigricans, and a family history of PCOS.49,50 Other pathologic causes of AUB are described in Table 101-6.
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In up to 20% of adolescents with AUB, there is an associated underlying systemic disease; 50% of these will have a coagulopathy such as thrombocytopenia, Von Willebrand disease (VWD), or leukemia. The prevalence of menorrhagia in women with VWD is 74% to 92%, conversely, the prevalence of VWD in women with menorrhagia is 5% to 24%, with an overall prevalence of 13%.51,52 A recent study of adolescents with menorrhagia cites a 33% prevalence of VWD in this group.53 The prevalence of VWD in women with AUB has been cited as 5% to 20%; of women with VWD, 60% to 95% reported AUB.54,55
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Clinical Presentation
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A detailed and complete menstrual history is critical and includes age of menarche, frequency, amount, and duration of menses, pain with menses, impact on life, and last menstrual period. Sexual history including number of partners, contraceptive use, history of sexually transmitted diseases, medication use, reproductive history, underlying medical history, and family history should also be included. Signs of hypovolemia including hypotension, tachycardia, diaphoresis, or pallor, and symptoms of bleeding such as epistaxis, easy bruising, or a history of excessive bleeding with surgical interventions or dental procedures are important. Special attention should be given to signs of PCOS, such as acne, hirsutism, acanthosis nigricans, and symptoms often seen in thyroid disorders, such as weight gain, cold or heat intolerance, or hair loss.40,56,57
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A complete physical examination begins with vital signs and an assessment of respiratory, and hemodynamic stability and, degree of anemia. In the stable patient, assess for evidence of pathological causes of AUB. A pelvic examination must be performed to exclude sexually transmitted infection or structural abnormalities; if the adolescent is not sexually active, the pelvic examination may be deferred. The hallmark of AUB is a negative pelvic examination. Attention should be given to physical findings of systemic disease such as bruising, purpura, jaundice, and sepsis.40,56,57
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Diagnostic Evaluation
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In the patient with unstable vital signs, perform a CBC with platelets, prothrombin time (PT), activated thromboplastin time (aPTT), type and cross-match, and pregnancy test. In stable patients, a pregnancy test and CBC should be considered. The hemoglobin and hematocrit are helpful in estimating blood loss and severity of bleeding. A platelet count helps rule out thrombocytopenia.58
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Pregnancy, including ectopic pregnancy, threatened or spontaneous abortion, and complications of a recent induced abortion can present with vaginal bleeding. It is important to rule out pregnancy in all adolescents who present with unexplained heavy bleeding, especially in those with previously regular cycles.58 Sexually transmitted diseases such as Chlamydia trachomatis and Neisseria gonorrhoeae are also associated with cervicitis and endometrial intermenstrual bleeding. Screen for gonorrhea and chlamydia infections by urine nucleic acid amplification tests (NAATs) or cervical cultures.
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To test platelet function, the platelet function analysis (PFA) is the study of choice. Bleeding times are nonspecific whereas the platelet function analysis-100 (PFA-100) has demonstrated a 96% sensitivity and a 98% specificity for measuring platelet function.59 Evaluation of VWD includes obtaining CBC, PT, aPTT, fibrinogen, a ristocetin cofactor assay of von Willebrand factor (VWF), vW antigen, and a factor 8 (FVIII) level.55 Finally, consider thyroid function tests to rule out thyroid disease and FSH, LH, testosterone, and DHEAS levels to rule out PCOS. A detailed evaluation for AUB is beyond the scope of the ED visit, but the history and physical examination can be used to guide the choice of additional laboratory tests.
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Generally, patients with AUB can be managed appropriately without the use of expensive imaging studies. Pelvic sonography is often performed to rule out anatomical or structural pathology of the reproductive tract such as benign or malignant tumors or PCOS.60
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Management of Abnormal Uterine Bleeding
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Patients in hemorrhagic shock, with severe anemia (hemoglobin <7 g/dL)or with heavy bleeding are hemodynamically unstable. Evaluate the airway, breathing, circulation, and address priorities of resuscitation (see Chapter 19 on management of shock). Obtain vascular access and begin rapid infusion of isotonic crystalloid. After 2 or 3 fluid boluses, consider a packed red blood cell transfusion (PRBC) and administer intravenous estrogen (Premarin) in a dose of 25 mg every 4 to 6 hours until bleeding stops for 24 hours. Once bleeding is controlled, start the patient on an OCP with a strong progestin. If bleeding is not controlled, consider admission and consult a gynecologist for further treatment such as dilatation and curettage.32,36,57,60
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Treatment of hemodynamically stable patients with anovulatory AUB can be managed with OCPs consisting of progestogens alone or in combination with estrogens and referred to a gynecologist for outpatient management.61 OCPs are useful for cycle regulation, contraception, and prevention of associated prolonged unopposed estrogen stimulation of the endometrium. OCPs are contraindicated in smokers, women older than 35 years, and those with high risk of thromboembolism. In these women, progestins are recommended.62 (See Fig. 101-2 and Table 101-7 for management algorithm and additional treatment regimens.)
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In summary, management of patients with mild bleeding, includes reassurance, NSAIDs, a monophasic OCP, and iron. For patients with moderate bleeding, consider starting OCPs at a higher dose (two pills per day) until the bleeding stops and then one pill per day for 3 to 6 months. Patients with heavy bleeding may benefit from starting one pill every 6 hours for 4 days, followed by one pill every 8 hours for 4 days, and a tapering schedule for the rest of the month. Once bleeding is controlled, the patient should take one pill per day for 3 to 6 months.
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Treatment of hemodynamically stable patients with ovulatory AUB includes NSAIDs, levonorgestrel-releasing intrauterine systems, OCPs, androgens, antifibrinolytics, desmopressin, and surgery.