DEFINITION AND EPIDEMIOLOGY

Dysmenorrhea is defined as cyclic menstrual cramps and pain associated with menstruation. It may be classified by pathophysiology (primary or secondary) or by intensity (mild, moderate, or severe) (Table 102-1).¹ The term primary dysmenorrhea refers to pain with menses in the absence of pelvic pathology. It typically begins in adolescence once regular ovulatory cycles are established. Secondary dysmenorrhea, by definition, is associated with underlying pelvic pathology. It can occur any time after menarche but most commonly affects older women.²

The estimated prevalence of primary dysmenorrhea is 43% to 93%, and up to 50% to 70% of adolescents in the United States suffer from this debilitating condition.^1,3–5 According to one study, only 14% of adolescents in the United States, 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 reporting self-medicating with over-the-counter preparations.⁶

Approximately one-third to one-half of females with primary dysmenorrhea are missing school or work at least once per menstrual cycle, with 5% to 14% of these women missing more frequently.¹ This symptom burden has been estimated to account for 600 million lost working hours and 2 billion dollars in lost productivity annually in the United States.^3–8 Moreover, females with dysmenorrhea are at increased risk for developing additional chronic pain disorders such as fibromyalgia, which further increases the long-term burden of this condition.²

The cause of primary dysmenorrhea is unclear. However, the condition is associated with prostaglandin F2-alpha 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 has a similar role as prostaglandins. Hormones, cervical morphology, nervous system, and psychological factors may also play a role.⁸ In secondary dysmenorrhea, prostaglandins are involved but by definition, concomitant pelvic pathology must also be present.

ETIOLOGY/RISK FACTORS

Primary dysmenorrhea affects women of all races. Multiple risk factors for primary dysmenorrhea have been described (Table 102-2).^4,5,7,9–11 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.¹² 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.^9,13

CLINICAL PRESENTATION

The pain of dysmenorrhea may be experienced in the pelvis, lower abdomen and back, or anterior upper legs and is typically cramping in nature. In primary dysmenorrhea, pain begins once ovulatory cycles are established, usually within 6 months to 1 year after menarche. This pain occurs at the onset of menses and lasts 8 to 72 hours (median duration of 2 days).^2,4 Other associated symptoms include headache, diarrhea, nausea, fatigue, dizziness, and vomiting.³ In 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.

DIAGNOSTIC EVALUATION

Primary dysmenorrhea is usually benign and requires little diagnostic evaluation other than a careful history.^3–14 Imaging studies are not helpful. 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). Pelvic exam is recommended in the evaluation of secondary dysmenorrhea but may be deferred in young adolescents with mild symptoms who are not sexually active.¹⁵ Abdominal and transvaginal ultrasonography are recommended to identify anatomic abnormalities, but other modalities may be indicated depending on the suspected underlying pathology (Table 102-3).

MANAGEMENT

Pharmacologic Treatment

Use NSAIDs as the first line of treatment for dysmenorrhea; they reduce prostaglandin production via cyclooxygenase inhibition, which also decreases pain and cramping. 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.¹⁴

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. These agents were marketed in the late 1990s with the goal of reducing the common side effects of nonselective COX inhibition. However, a meta-analysis by the Cochrane Collaboration found that there is no evidence that COX-2–specific inhibitors are more effective or tolerable for the treatment of dysmenorrhea than traditional NSAIDs.¹⁶ In addition, serious concerns about gastrointestinal and cardiovascular side effects of these agents have been raised (Table 102-4).^16–21 The FDA revoked approval of Rofecoxib and Valdecoxib because of associated increases in cardiac complications, and requires the other marketed COX-2 inhibitors to have labeling stating an associated increase in cardiovascular adverse events.

Although an off-label therapy, oral contraceptive pills (OCPs) are a common, effective, and safe therapy for dysmenorrhea.²² 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.^23–28 Continuous oral progestins, such as norethisterone acetate, are effective alternatives to combined OCPs for the treatment of dysmenorrhea in young women.²⁹ Additionally, Levonorgestrel-releasing intrauterine devices (IUDs) are now recognized to provide non-contraceptive benefits, including treatment of dysmenorrhea in adolescents and women.³⁰ Do not place an IUD in the young, non-sexually active adolescent without consulting a gynecologic specialist. For refractory cases, consider treatment to suppress the menstrual cycle with danazol (an androgen) and leuprolide acetate (a gonadotropin-releasing hormone). Preliminary data evaluating oral nifedipine and intravenous terbutaline have shown promise in reducing myometrial contractions; however, prospective clinical trials are still needed.³¹ A recent study with an oral leukotriene receptor antagonist, montelukast, showed a significant reduction in pain and overall NSAID use in a group of 50 women; again, larger prospective studies are needed.³²

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. Oral zinc supplements may decrease both the duration and severity of pain when taken daily for at least 3 months.³³ Vitamin E studies are limited and conflicting.³⁴ Behavioral interventions such as pain management training, relaxation, imagery, and biofeedback may improve symptoms, resulting in less time absent from school and work.³⁵ Heat therapy and transcutaneous electrical nerve stimulation (TENS) are both reported to reduce pain, with new portable TENS devices being marketed specifically for menstrual cramping.^36,37 Interventions such as chiropractic–spinal manipulative therapy and acupuncture have been used, with little research published to establish efficacy.^34,38,39