Dysmenorrhea in Emergency Medicine

Background
Dysmenorrhea refers to the syndrome of painful menstruation. Its prevalence is estimated at 25% of women and up to 90% of adolescents.[1] No significant difference exists in prevalence or incidence between races, though the most common causes of dysmenorrhea differ by age (see History). Although it is not life-threatening, dysmenorrhea can be debilitating and psychologically taxing for many women. Some choose to self-medicate at home and never seek medical attention for their pain. Dysmenorrhea is responsible for significant absenteeism from work, and it is the most common reason for school absence among adolescents.[1] Dysmenorrhea can be divided into 2 broad categories: primary and secondary. Primary dysmenorrhea occurs in the absence of pelvic pathology, whereas secondary dysmenorrhea results from identifiable organic diseases.

Pathophysiology
Historical attitudes toward menstrual pain were often dismissive. Pain was often attributed to women's emotional or psychological states and misconceptions about sex and sexual behaviors. Research has now established concrete physiologic explanations for dysmenorrhea, which discredit these prior theories.[1, 2] Primary dysmenorrhea usually begins within the first 6 months after menarche once a regular ovulatory cycle has been established. During menstruation, sloughing endometrial cells release prostaglandins, which cause uterine ischemia through myometrial contraction and vasoconstriction. Elevated levels of prostaglandins have been measured in the menstrual fluid of women with severe dysmenorrhea. These levels are especially high during the first 2 days of menstruation. Vasopressin may also play a similar role.[1, 3] Secondary dysmenorrhea may present at any time after menarche, but it most commonly arises when a woman is in her 20s or 30s, after years of normal, relatively painless cycles. Elevated prostaglandins may also play a role in secondary dysmenorrhea, but, by definition, concomitant pelvic pathology must also be present. Common causes include endometriosis, leiomyomata (fibroids), adenomyosis, pelvic inflammatory disease, and intrauterine device (IUD) use. Note that, though the hormonal link to dysmenorrhea may partially explain its pathophysiology, hormones do not explain the total story. There is a very complex interplay between these hormones, basal body temperature, sleep patterns, and the central nervous system, the extent of which is not completely understood.

Epidemiology
Frequency United States

Its prevalence is estimated at 25% of women and up to 90% of adolescents.[1]

Mortality/Morbidity

Dysmenorrhea itself is not life threatening, but it can have a profoundly negative impact on a woman's day-to-day life. In addition to missing work or school, she may be unable to participate in sports or other activities, compounding the emotional distress brought on by the pain.
Race

No significant difference exists in prevalence or incidence between races.

Age

The most common causes of dysmenorrhea differ by age (see History).

History
Primary dysmenorrhea may be distinguished from secondary dysmenorrhea by means of a thorough history. Pertinent information includes not only character and onset of pain but also history of similar pain, associated symptoms (eg, dyspareunia), age at menarche, abnormal vaginal bleeding or discharge, obstetric and contraceptive history, and HIV status.[4] A family history should be sought for bleeding diatheses or sickle cell disease. Some differentiating factors of primary and secondary dysmenorrhea are listed below:
Primary dysmenorrhea

Onset within 6 months after menarche Lower abdominal/pelvic pain begins with onset of menses and lasts 8-72 hours Low back pain Medial/anterior thigh pain Headache Diarrhea Nausea/vomiting

Secondary dysmenorrhea

Onset in 20s or 30s, after relatively painless menstrual cycles in the past Infertility Heavy menstrual flow or irregular bleeding

Dyspareunia Vaginal discharge Pain may not be relieved by nonsteroidal anti-inflammatory drugs (NSAIDs)

Physical
A complete physical examination should be performed. For younger adolescents who have never been sexually active, a careful abdominal examination is appropriate. In older adolescents or those known to be sexually active, a pelvic examination is crucial. This examination includes inspection of the external genitalia for rashes, swelling, or discoloration; the vaginal vault for discharge, blood, or foreign bodies; the cervix for the above, plus any masses or signs of infection; and a bimanual examination to assess cervical motion tenderness, uterine or adnexal tenderness, or any masses in the pelvis.[4] Pelvic ultrasonography should be considered in women who are suspected of having secondary dysmenorrhea. Attention should also be paid to the abdominal examination and back/flank examinations to rule out pelvic pain as a presentation of gastrointestinal (GI) and upper genitourinary (GU) pathology, respectively.
Primary dysmenorrhea

May have lower abdominal tenderness May have uterine tenderness or normal pelvic examination findings Cervical stenosis may contribute to retrograde flow.

Secondary dysmenorrhea

Palpable uterine mass or masses Cervical motion tenderness Adnexal tenderness or palpable mass or masses Vaginal or cervical discharge Visible vaginal pathology (mucosal tears, masses, prolapse) Normal abdominal and pelvic examinations do not rule out pathology. Ultrasonography or other imaging modalities may be warranted if suspicion of secondary dysmenorrhea is high.

Causes
Risk factors for dysmenorrhea

Primary dysmenorrhea

Early age at menarche (< 12 y) Nulliparity Heavy or prolonged menstrual flow Smoking Positive family history Obesity

Secondary dysmenorrhea

Leiomyomata (fibroids) Pelvic inflammatory disease Tubo-ovarian abscess Ovarian torsion Ovarian cysts Endometriosis Adenomyosis Intrauterine device

Causes of secondary dysmenorrhea

This section provides brief synopses on the more common causes of secondary dysmenorrhea. Uterine leiomyoma Uterine leiomyoma are benign tumors of the uterine musculature. They are up to 9 times more common in black women than white women.[5] It is a common cause of dysmenorrhea as they enlarge when stimulated by estrogen. In addition to pain with menses, patients may also present with menorrhagia, abdominal distension, or pressure. Pelvic examination may reveal a uterine mass or irregularity. Ultrasonography is often used for determining size and location of fibroids, though CT scan is used if ultrasound information is limited.[4, 6] Unless patients are symptomatic from profound anemia, these patients can be safely discharged with appropriate gynecologic follow up. Potential complications are anemia and infertility.[7] Pelvic inflammatory disease Pelvic inflammatory disease (PID) is an infection of the uterus, fallopian tubes, with or without ovarian or parametrial involvement. It is an ascending infection that develops during or immediately after menses, and if chronic, can lead to dysmenorrhea. The most common infectious organisms are Chlamydia trachomatis and Neisseria gonorrhoeae, although it can be caused by other organisms, such as Gardnerella vaginalis, anaerobes, and gram-negative rods.[4] Previously, the diagnosis, while primarily clinical, was based on having 3 major criteria (abdominal pain, adnexal pain, and cervical motion tenderness), and 1 minor criterion (fever, vaginal discharge, leukocytosis, positive cervical cultures, gram-negative stain, intracellular diplococci, or white cells on vaginal smear).[4] More recent data from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) trial shows that the presence of adnexal tenderness has a sensitivity of 95.5% for histologic endometritis. This trial supports the empiric treatment of all women at risk for pelvic inflammatory disease with adnexal tenderness and no other obvious cause. Based on data from the PEACH trial, the Centers for Disease and Control and Prevention (CDC) recommends that all women at risk for pelvic inflammatory disease and who exhibit adnexal, uterine, or pelvic

tenderness on bimanual examination, and no other explanation for these findings, be treated empirically for pelvic inflammatory disease.[8] In addition to appropriate analgesia (see Treatment below) patients need to be treated with appropriate antibiotic coverage; the most commonly used regimen is ceftriaxone 250 mg IM and doxycycline 100 mg per day for 14 days.[4] Patients should be hospitalized if outpatient therapy fails, if they have intractable nausea or vomiting, if they have a complicating tubo-ovarian abscess, or if they are immunocompromised.[4] Complications include tubo-ovarian abscess and Fitz-Hugh Curtis syndrome (perihepatitis) if pus from the fallopian tubes leaks into the peritoneum. Tubo-ovarian abscess Tubo-ovarian abscess is a loculated infection within the fallopian tubes and/or ovaries, and is usually sequela of pelvic inflammatory disease. It is often polymicrobial. Patients present most commonly with fever and gradually worsening pelvic pain and tenderness, although nausea, vomiting, and vaginal bleeding or discharge may be present as well. Examination may elicit tenderness upon cervical motion and in the adnexal area. Pelvic mass may be present, although this is often difficult to palpate.[4] Tubo-ovarian abscesses can be detected on pelvic sonogram or abdominal CT scan as a complex cystic structure in the pelvis, with or without loculations.[6] Patients are often admitted for intravenous antibiotics that cover Neisseria gonorrhoeae, Chlamydia, anaerobes, and gram-negative organisms. If medical therapy fails or if peritoneal signs are found on examination, then surgical drainage is indicated.[4] Infertility is almost always a complication of tubo-ovarian abscess.[4] The most feared complication is rupture, which can lead to septic shock and death; it is a true surgical emergency if this occurs.[7] Ovarian torsion Ovarian torsion involves twisting of the adnexal structures, leading to ischemia and ultimately necrosis if the process is not reversed in time. In a nonpregnant woman, it is almost always caused by an abnormality in the ovary such as a cyst or a tumor. Torsion can occur in pregnancy without a requisite adnexal abnormality, and, in one large series, 20% of the patients found to have torsion were pregnant.[9] Patients often present with severe, intermittent, colicky, unilateral pelvic or lower abdominal pain, associated with nausea and vomiting. The diagnosis is often delayed because it can resemble other disease entities, such as appendicitis or renal colic.[4, 7] Because of these differential diagnoses, CT scan is often performed before any other imaging modality. It is important to be familiar with the CT findings for torsion[6] : an ovarian enlargement of >5 cm with a corkscrew appearance of the ipsilateral fallopian tube.[6] Sonogram will usually show a large ovarian mass or cyst, but ultrasonographic evidence of torsion is difficult to obtain because the appearance changes depending on the length of time elapsed.[7]

If suspicion for ovarian torsion is high, gynecologic consultation should be obtained early because laparoscopy is not only diagnostic but also therapeutic and potentially fertility-saving.[7] These patients are all admitted. Ovarian cyst rupture/hemorrhage A hemorrhagic ovarian cyst comes from an ovarian follicle in the absence of ovulation; thus, they are exclusively found in menstruating females. They often present with acute onset of pelvic or abdominal pain, along with nausea and vomiting. Examination may reveal an adnexal mass, but almost all patients with ruptured ovarian cysts have some level of adnexal tenderness. Patients may have signs of peritoneal irritation as well. Although CT scan and ultrasonography can be used to visualize hemoperitoneum and the cyst,[6] laparoscopy is needed for the definitive diagnosis.[4] Endometriosis Endometriosis is the presence of endometrial-like tissue found outside of the uterus, most commonly in the ovaries. Women often present with dyspareunia and pelvic and back pain. Although endometriosis is a diagnosis of exclusion, patients may give a history of dysmenorrhea in the past that is cyclic with menses.[4] However, it is important to note that this disease can exist concomitantly with other disease processes causing dysmenorrhea, making the diagnosis even more difficult.[10] The history may also include chronic pelvic pain unresponsive to antibiotics or analgesics. A good obstetric history may also elicit frequent miscarriages or difficulty conceiving.[4, 10] The classic examination finding is a fixed uterus with ash spots (purple-blue discolorations) on the cervix, though this is not always present.[4] Although CT scanning may hold some promise as a diagnostic tool in the future,[6] laparoscopy or laparotomy are still the only means by which endometriosis can be definitively diagnosed. There is controversy as to whether definitive diagnosis is even necessary.[10] Many times, the assumption is that the endometriosis, if found, is the cause of patient discomfort when it may not be. Conversely, if endometriosis is the cause of dysmenorrhea, surgery may not be necessary if pain is controlled with hormonal therapy, analgesia, or both.[10] The main complication of endometriosis is rupture of an endometrioma. Adenomyosis Adenomyosis is defined as an invasion of myometrium by uterine adrenal glands. It is a rare disease and can resemble uterine leiomyomas and endometrial carcinoma in its presentation; thus, it is difficult to diagnosis. Definitive diagnosis is by transvaginal ultrasonography or MRI. When the latter is used, one is looking for a thickened junctional zone (JZ line), or the border between myometrium and endometrium. One paper showed that adenomyosis should be in the differential diagnosis when a patient is treated for presumptive endometriosis and has chronic persistent pain.[11] Intrauterine device

Intrauterine devices (IUDs) may cause bladder or uterine perforation. The sooner a patient has a uterine rupture from the time of IUD placement, the more likely they can present with peritoneal signs.[4] Patients with bladder perforation may have recurrent cystitis unresponsive to antibiotics. It is very important to remove the IUD immediately to prevent further damage to the uterine or bladder walls. Abdominal radiographs may reveal the location of an IUD if the string is not seen in the vaginal vault. A gynecologist should be consulted early.[4] Premenstrual dysmorphic disorder (formerly premenstrual syndrome) In addition to dysmenorrhea, patients may also have bloating, body aches, migraine headaches, breast tenderness, and emotional complaints. The effects of these symptoms in rare instances can be debilitating. Besides possible vaginal brownish discharge or bleeding, the pelvic examination findings will be normal. It is the emergency physician's responsibility to ensure adequate analgesia and appropriate follow up with a gynecologist. See Premenstrual Dysphoric Disorder for additional information.

Laboratory Studies
Laboratory studies may be indicated to elucidate the cause of secondary dysmenorrhea.

Complete blood count (with differential), for evidence of infection or neoplastic process Urinalysis, to exclude urinary tract infection Quantitative human chorionic gonadotropin level, to exclude ectopic pregnancy Gonococcal/chlamydial cultures, enzyme immunoassay (EIA), and DNA probe testing, to exclude sexually transmitted infections (STIs)/pelvic inflammatory disease (PID) Stool guaiac, to rule out GI bleeding Erythrocyte sedimentation rate (ESR), for subacute salpingitis

Although these tests can be used as adjuncts in the workup of dysmenorrhea, they may be misleading. For instance, the CBC may show a normal white count in up to 56% of patients with PID. Conversely, the white count can be elevated from physiologic stress. In a patient with associated vaginal bleeding, the hematocrit may be normal in a patient with obvious hypovolemia on examination (eg, positive orthostasis or tachycardia), especially if hemorrhage started within minutes to hours of presentation.[4] Moreover, the EIA and DNA probe tests for gonorrhea and chlamydia have varying sensitivities, anywhere from 86-93%.[4] Therefore, ancillary laboratory testing should not replace a sound clinical basis for diagnosis of dysmenorrhea and its underlying cause.

Imaging Studies
In cases of well-established primary dysmenorrhea, imaging studies are of little value. However, if pelvic pathology is suspected, abdominal and/or transvaginal ultrasonography are inexpensive and effective modalities.

Ultrasonography is relatively noninvasive, can easily be performed in the ED, and reveals most relevant pelvic pathology. For instance, endometriosis may appear as a complex mass with a speckled appearance.[4] Although CT scanning is not routinely ordered in the ED for patients with dysmenorrhea, it does have some utility, particularly in identifying ovarian torsion.[4, 7, 6] MRI has some ability to detect adenomyosis and submucous myomas that might otherwise be missed on other imaging modalities.[4] This test is not routinely ordered in the ED.

Procedures
Further investigation outside the ED might include hysterosalpingoscopy or laparoscopy. The latter is usually indicated when initial interventions fail to relieve symptoms.

Emergency Department Care

As always, ED evaluation should begin with the ABCs and should consider serious diagnoses such as hemorrhagic shock and sepsis. A patient whose history and clinical presentation clearly suggest primary dysmenorrhea may be treated symptomatically and provided with appropriate follow-up. A patient whose presentation is less clear or whose vital signs and/or physical examination findings are abnormal deserves a more thorough workup, including full laboratory studies, pelvic ultrasonography, and potentially an OB/GYN consultation.

Consultations
Patients with pelvic pain do not routinely need consultation with a gynecologist in the emergency department, though they should be directed to follow up as an outpatient. Exceptions include certain infectious entities, such as abscesses, as well as endometriosis.

Medication Summary
Treatment of dysmenorrhea is aimed at providing symptomatic relief as well as inhibiting the underlying processes that cause symptoms. NSAIDs reduce prostaglandin production via cyclooxygenase inhibition and are used as first-line therapy for both primary and secondary dysmenorrhea. If taken early enough and in sufficient quantity, they are extremely successful in alleviating menstrual pain. In the ED setting, patients who do not respond to NSAIDs may require treatment with narcotics for pain control. Patients whose symptoms are not relieved by NSAIDs are very likely to have underlying pelvic pathology such as endometriosis. In a study comparing montelukast, a leukotriene-receptor antagonist, to placebo in patients with dysmenorrhea, montelukast was effective in reducing pain.[12] Clinicians may consider this as an alternative to hormonal therapy or in lieu of NSAIDs.

COX-2 specific inhibitors have also proven effective in relieving menstrual pain. Their selectivity reduces the GI symptoms caused by inhibition of the COX-1 receptor. However, recent clinical trials have raised their cardiovascular safety profiles into question. As a result, some of these agents are no longer available. Simple analgesics, such as aspirin and acetaminophen, may also be useful, especially when NSAIDs are contraindicated. Oral contraceptives, which block monthly ovulation and may decrease menstrual flow, may also relieve symptoms. One recent update of a CochraneDatabase of Systematic Reviews article showed some evidence of symptomatic benefit in patients with primary dysmenorrhea, though no specific preparation showed superiority over another.[13] Certain dietary supplements may be effective, though their effectiveness has only been demonstrated in small clinical trials. Thiamine, fish oil, pyridoxine, magnesium, and vitamin E are examples.[3, 14]

Nonsteroidal anti-inflammatory agents

Class Summary

These drugs are highly effective in treating dysmenorrhea, especially when they are started before the onset of menses and continued through day 2. They are readily available, relatively inexpensive, and have a low side effect profile when used cautiously and in those who have no contraindications.
View full drug information Ibuprofen (Ibuprin, Advil, Motrin)

DOC for treatment of mild to moderate pain, if not contraindicated. Inhibits inflammatory reactions and pain, probably by decreasing activity of the enzyme cyclooxygenase, which results in inhibition of prostaglandin synthesis.
View full drug information Naproxen (Anaprox, Naprelan, Naprosyn, Aleve)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis. Cost is approximately $3.00/d compared with $0.14/d for generic ibuprofen.
View full drug information

Diclofenac (Cataflam, Voltaren)

Designated chemically as 2-[(2,6-dichlorophenyl) amino] benzene acetic acid, monosodium salt, with an empirical formula of C14 H10 Cl2 NO2 NA. One of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacologic studies. Believed to inhibit the enzyme cyclooxygenase, which is essential in prostaglandin biosynthesis. Can cause hepatotoxicity; hence, liver enzymes should be monitored in first 8 weeks of treatment. Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Delayed-release, enteric-coated form is diclofenac sodium, and immediate-release form is diclofenac potassium. Has relatively low risk for bleeding GI ulcers.
View full drug information Hydrocodone and acetaminophen (Vicodin, Lorcet-HD, Lortab)

Drug combination indicated for moderate to severe pain.

Further Outpatient Care

Patients with both primary and secondary dysmenorrhea should be provided with appropriate gynecologic follow-up. If they do not have regular medical care, an appointment with a primary medical doctor is also indicated.

Inpatient & Outpatient Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) Opioid analgesics

Deterrence/Prevention
Various measures have been used to manage dysmenorrhea in the outpatient setting. Lifestyle modification seems to be helpful. Smoking cessation should be encouraged, since this may be a risk factor for dysmenorrhea.[1, 15] Exercise has been shown to alleviate symptoms of dysmenorrhea, though the mechanism is not well understood.[15] A CochraneDatabase of Systematic Reviews article of 5 randomized controlled trials showed that certain behavioral interventions may be effective at treating primary and secondary dysmenorrhea.[2] Other potentially effective interventions include a low-fat vegetarian diet and acupuncture.[5, 16]

Complications

If a diagnosis of secondary dysmenorrhea is missed, the underlying pathology may lead to increased morbidity, including difficulty conceiving.[10]

Prognosis

The prognosis for primary dysmenorrhea is excellent with the use of NSAIDs. The prognosis for secondary dysmenorrhea varies depending on the underlying disease process.

Patient Education

Dysmenorrhea: Painful Menstrual Periods Menstrual Irregularities, Health Information, National Institutes of Health (NIH)