Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine) 4th Ed.

CHAPTER

101

Dysmenorrhea and Abnormal Uterine Bleeding

Mercedes Uribe

Pamela J. Okada

HIGH-YIELD FACTS

• The pain of dysmenorrhea may be experienced in the pelvis, lower back, or anterior thighs.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for dysmenorrhea.

• In a normal menstrual cycle there is an average of 5 to 80 mL of blood loss.

• Abnormal uterine bleeding (AUB) is a diagnosis of exclusion and involves any disturbance in regularity, frequency, duration, or volume of menstrual flow.

• Up to 20% of adolescents with dysfunctional uterine bleeding will have a coagulopathy.

• The hallmark of AUB is a negative pelvic examination.

DYSMENORRHEA

image DEFINITION AND EPIDEMIOLOGY

Dysmenorrhea is defined as cyclic menstrual cramps and pain associated with menstruation. Dysmenorrhea may be classified by pathophysiology (primary or secondary) or by intensity (mild, moderate, or severe) (Table 101-1).1The term primary dysmenorrhea refers to pain with menses in the absence of pelvic pathology and typically begins early in adolescence once the regular ovulatory cycle has been established. Secondary dysmenorrhea is usually associated with underlying pelvic pathology, occurs at any time after menarche, and is most often seen in older women.2,3

TABLE 101-1

Classification of Dysmenorrhea

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The prevalence of primary dysmenorrhea is estimated to be 43% to 93% with 50% to 70% of adolescent women suffering from this debilitating condition.47 According to one study, only 14% of US adolescents, aged 12 to 17 years with dysmenorrhea, sought help from a physician. Self-treatment for dysmenorrhea is common among adolescent girls and young women, with 30% to 60% of girls report self-medicating with over-the-counter preparations.8

Dysmenorrhea has significant impact for both the individual and society. Approximately 38% of adolescents and 51% of young women describe severe symptoms, causing regular absenteeism from school and work respectively. This symptom burden, which interferes with work several days each cycle, has been estimated to account for 600 million lost working hours and 2 billion dollars in lost productivity annually in the United States.410

PATHOPHYSIOLOGY

The cause of primary dysmenorrhea is unclear; however, the condition is associated with prostaglandin F2 release in the endometrium during menstruation. Sloughing endometrial cells release prostaglandins, causing myometrial contraction and vasoconstriction, which results in pain and cramping. The involvement of vasopressin is postulated to be increased in menstrual fluids and having a similar role as prostaglandins. Hormones, cervical morphology, nerves, and psychological factors may also play a role, but also act through prostaglandins.10 In secondary dysmenorrhea, prostaglandins also play a role, but by definition, concomitant pelvic pathology must also be present.

image ETIOLOGY/RISK FACTORS

Primary dysmenorrhea affects women of all races. Multiple risk factors for primary dysmenorrhea have been described (Table 101-2).57,9,1113 Risk of secondary dysmenorrhea is increased if there is a history of sterilization, sexual assault, intrauterine device, or presence of pelvic pathology as described previously.14 Decreased risk of dysmenorrhea is found in women with oral contraceptive use, increased fish intake, higher physical activity, higher parity, older age, and those married or in a stable relationship.11,15,16

TABLE 101-2

Risk Factors for Dysmenorrhea

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image CLINICAL PRESENTATION

The pain of dysmenorrhea may be experienced in the pelvis, lower back, or anterior upper legs. In primary dysmenorrhea, pain usually begins within the first 6 months after menarche and once ovulatory cycles are established and occurs at the onset of menses lasting 8 to 72 hours (median duration of 2 days).5,16 Other associated symptoms include headache, diarrhea, nausea, fatigue, dizziness, and vomiting.4In secondary dysmenorrhea, pain usually occurs in the older population after painless menstrual cycles have been established. In addition, some women experience infertility, dyspareunia, itchiness, vaginal discharge, irregular bleeding, heavy bleeding, and dysuria during times other than menses.

image DIAGNOSTIC EVALUATION

Primary dysmenorrhea is usually benign and requires little diagnostic evaluation other than a careful history.217 Secondary dysmenorrhea requires a more detailed assessment to determine the underlying pathology and may include a complete blood count (CBC), urinalysis, pregnancy test, gonococcal and chlamydial cervical cultures, and an erythrocyte sedimentation rate (ESR). Imaging studies are not helpful in the evaluation of primary dysmenorrhea. For secondary dysmenorrhea, abdominal and transvaginal ultrasonography are recommended to identify anatomic abnormalities, but other modalities may be indicated depending on the suspected underlying pathology (Table 101-3).

TABLE 101-3

Diagnostic Modalities for Secondary Dysmenorrhea

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image MANAGEMENT

Pharmacologic Treatment NSAIDs are the first line of treatment for dysmenorrhea. NSAIDs reduce prostaglandin production via cyclooxygenase inhibition, and this, in turn, also decreases menstrual flow. Common adverse side effects during short-term usage include gastrointestinal disturbance (e.g., gastritis and indigestion) and drowsiness. Rare but serious side effects with prolonged use include cardiovascular complications, liver and renal failure, and serious skin reactions.2,17

A newer class of NSAIDs, the cyclooxygenase-2 (COX-2) inhibitors, inhibits the cyclooxygenase-2 enzyme, which aids in the metabolism of arachidonic acid to prostaglandin. The use of COX-2 inhibitors in women with dysmenorrhea has demonstrated significant decreases in pain, but concerns of the gastrointestinal and cardiovascular side effects of these agents have been raised (Table 101-4).2,3,1822 The FDA revoked approval of Rofecoxib and Valdecoxib because of associated increases in heart complications and other COX-2 inhibitors’ labeling specifically describe an associated increase in cardiovascular risk.

TABLE 101-4

Pharmacology Medications for Dysmenorrhea

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Although an off-label therapy, for women who desire contraception, oral contraceptive pills (OCPs) are a common, effective, and safe therapy for dysmenorrhea.23 OCPs work by inhibiting ovulation and reducing the endometrial lining of the uterus. A reduction of endometrial thickness equates to a reduction in prostaglandin release, which reduces uterine contractility and associated pain. Adverse side effects are minor and include headache, nausea, breast tenderness, mood changes, tiredness, and nervousness; rare but serious adverse effects include thrombosis, hepatic tumors, and cervical cancer. These adverse side effects generally decrease in frequency and severity with long-term use of OCPs.2430 Treatment to suppress the menstrual cycle with Danazol (an androgen) and Leuprolide acetate (a gonadotropin releasing hormone) may be considered in refractory cases. Finally, preliminary data evaluating oral nifedipine and intravenous terbutaline have shown promise in reducing myometrial contractions; however, prospective clinical trials still need to be conducted.31

Nonpharmacologic Treatment The efficacy of conventional treatment using NSAIDs is considerable; however, the failure rate is still 20% to 25%. Consumers are now seeking alternatives to conventional medicine. Herbal and dietary therapies such as magnesium, vitamin B6, vitamin B1, omega-3 fatty acids, fish oil, and Japanese herbals have been shown to reduce pain during menses. Vitamin E does not show any effect.3,32 Behavioral interventions such as pain management training, relaxation, imagery, and biofeedback may improve symptoms resulting in less time absent from school and work.3,33 Finally interventions such as chiropractic-spinal manipulative therapy and acupuncture have been used with little research published to establish efficacy.34,35

Treatment of secondary dysmenorrhea depends upon an accurate diagnosis of the cause of pain. In the absence of a clear diagnosis for the cause of pain in secondary dysmenorrhea, nonacute pain can be managed empirically for a short period of time using the interventions previously mentioned. Surgical intervention with referral to a gynecologist for laparoscopy, presacral neurectomy, laparoscopic uterosacral nerve ablation, or hysterectomy may be considered in refractory cases.3

ABNORMAL UTERINE BLEEDING

image DEFINITION AND EPIDEMIOLOGY

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).3638

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FIGURE 101-1. Normal menstrual cycle.

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

TABLE 101-5

Patterns of Menstrual Bleeding

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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

image PATHOPHYSIOLOGY

Anovulatory Cycle 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.37,4345

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

Ovulatory Cycle 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

image ETIOLOGY/RISK FACTORS

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.49,50Other pathologic causes of AUB are described in Table 101-6.

TABLE 101-6

Pathologic Causes of Abnormal Uterine Bleeding

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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

image CLINICAL PRESENTATION

History 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

Physical Examination 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

image DIAGNOSTIC EVALUATION

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

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.

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.

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

image MANAGEMENT OF ABNORMAL UTERINE BLEEDING

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

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.61OCPs 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.)

TABLE 101-7

Treatment for Abnormal Uterine Bleeding

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FIGURE 101-2. Treatment of abnormal uterine bleeding. VS, vital signs; NSAIDs, nonsteroidal anti-inflammatory drugs; Hgb, hemoglobin; respiratory and cardiovascular stabilization, PRBC, packed red blood cells; OCP, oral contraceptive; IVF, intravenous fluids; D&C, dilation and curettage.

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.

Treatment of hemodynamically stable patients with ovulatory AUB includes NSAIDs, levonorgestrel-releasing intrauterine systems, OCPs, androgens, antifibrinolytics, desmopressin, and surgery.

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