What is Dysmenorrhea?

Pathophysiology

Dysmenorrhea is defined as painful menstruation, and can be primary or secondary. Primary dysmenorrhea is attributed to uterine contractions with no underlying pathology, whereas secondary dysmenorrhea is due to pelvic disease such as endometriosis, inflammatory disease or uterine polyps.​ The main focus of this chapter is primary dysmenorrhea.

Prevalence

The reported prevalence of dysmenorrhea ranges from 6–80%, with the most common being 50%. The peak incidence is in women between 20 and 24 years of age, and it decreases with age. Dysmenorrhea is the most common cause of missed school or workdays in young women. Approximately 10% of women will suffer from severe symptoms.​

Etiology

Dysmenorrhea occurs as prostaglandins are released from lysing endometrial cells in the luteal phase of an ovulatory cycle. During anovulatory cycles, the endometrial tissue contains smaller amounts of prostaglandins; therefore, these cycles are usually painless.​Prostaglandins have a direct effect on the endometrium and surrounding tissues, resulting in the signs and symptoms of dysmenorrhea.​

The role of prostaglandins in the pathogenesis of dysmenorrhea is well established. Women with dysmenorrhea have higher concentrations of PGF₂-alpha and PGE₂ in their menstrual fluid than women who do not complain of pain on menstruation.​Moreover, administering these prostaglandins by infusion induces the same discomfort and symptoms experienced by women with dysmenorrhea.

Women with dysmenorrhea have increased uterine activity, resulting in increased resting tone, increased strength and frequency of contractions, and/or dysrhythmic contractions.​

Dysmenorrhea usually begins 6–12 months after menarche and occurs only with ovulatory cycles. It tends to decrease with age and after childbirth.​

Risk Factors

Onset of dysmenorrhea has been linked with age <30 years, BMI <20, early menarche (<12 years of age), longer cycles and duration of bleeding, heavy or irregular menstrual flow, premenstrual syndrome (PMS), pelvic inflammatory disease, sterilization, sexual assault​ and smoking.​ Protective factors may include use of oral contraceptives, exercise, higher parity and fish intake.

Clinical Presentation

The diagnosis of dysmenorrhea is based on the presence of symptoms, a normal pelvic exam and the patient’s response to therapy.​Individuals who do not respond to a proven therapy should be investigated for causes of secondary dysmenorrhea.​ Menstrual pain occurs a few hours before or just after menstruation begins and usually lasts for 48–72 hours. The pain is described as cramping and is most intense over the lower abdomen, but it may radiate to the back and inner thighs.​ Associated symptoms include nausea and vomiting, fatigue, diarrhea and headache.​

Goals of Therapy

• Relieve symptoms
• Minimize time lost from work, school and other activities
• Identify patients who may have secondary dysmenorrhea and require further medical assessment

Patient Assessment

Assess patients with dysmenorrhea to confirm that their complaints are consistent with the etiology, signs and symptoms of primary dysmenorrhea . Cues that additional patient evaluation is required include onset of pain more than 2 years postmenarche, symptoms that occur outside the first 3 days of menses, and changes in the severity or pattern of the pain or in the characteristics of the menstrual fluid, e.g., degree of flow, odour, colour, flow pattern. Response to a proven therapy for primary dysmenorrhea is usually a confirmation of the diagnosis; therefore, if a trial fails, the patient requires further assessment.

Nonpharmacologic Therapy

There is some evidence that exercise may reduce symptoms of dysmenorrhea;​ however, large, well-designed trials are lacking. Regular aerobic exercise can also decrease stress, which may be a contributing factor.​ A small (n=92) randomized trial suggests particular yoga poses may be beneficial in relieving dysmenorrhea.​The high degree of safety of these poses makes this an attractive nonpharmacologic treatment. It is unclear whether diet is associated with dysmenorrhea; however, decreasing fat intake may be of some benefit.​

Warm baths or applying a heating pad, heat patch or hot water bottle to the abdomen may reduce discomfort. In a randomized controlled study, heating pads provided pain relief equivalent to the use of ibuprofen. When both heating pads and ibuprofen were used together there was no more pain relief than with either agent used alone; however, pain relief occurred faster when both therapies were combined.​

A single trial examining the use of a sericite belt (source of infrared rays) with a heat pack found a statistically significant decrease in visual analog scale pain scores for patients using the belt. The clinical significance of this finding is doubtful and the trial design may have led to heat packs rather than the belt causing the beneficial effect.​

Behavioural interventions such as massage with aromatic oils (lavender, clary sage, marjoram oils 2:1:1 and rose absolue, rose otto, clary sage, rose geranium and ginger 0.5:0.1:1:1:1),​relaxation therapy, biofeedback, pain management sessions and coping skills have been studied; however, good-quality trials are lacking.​ Surgical ablation of the pelvic nerve pathways requires further study and is not recommended.​Spinal manipulation has not been shown to provide benefit in dysmenorrhea.​

High-frequency transcutaneous electric nerve stimulation (TENS) may have some utility in the treatment of dysmenorrhea.​A Cochrane systematic review (42 trials in 4640 subjects) examining the effectiveness of acupressure and acupuncture found some evidence for benefit; however, due to the low quality of studies, further investigation is needed.​

For most women, drug therapy is required and nonpharmacologic measures are used adjunctively.​

Pharmacologic Therapy

Pharmacologic agents that decrease the amount of prostaglandins in endometrial tissue or inhibit prostaglandin synthesis are considered first-line therapies for the treatment of dysmenorrhea.

Nonsteroidal Anti-inflammatory Drug

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the pain of dysmenorrhea by decreasing prostaglandin concentrations in endometrial and menstrual fluid.

Moderate or excellent pain relief is achieved more often with NSAIDs versus placebo.​Many NSAIDs have been used in the management of dysmenorrhea. Some NSAIDs have theoretical advantages in terms of site of action such as acetic acids (e.g., indomethacin), propionic acids (e.g., ibuprofen, naproxen) and fenamates (e.g., mefenamic acid), which reduce prostaglandin concentrations in endometrial and menstrual fluid.​ Mefenamic acid not only inhibits the formation of prostaglandins but also blocks prostaglandins at the receptor site. The clinical significance of these pharmacologic differences is questionable and head-to-head comparisons of NSAIDs lend little support for recommending one agent over another in terms of efficacy.​

The NSAID should be administered with food at the onset of pain or menses and continued for 72 hours, as the peak concentration of prostaglandins occurs in the first 48 hours.​ An initial loading dose may help obtain faster relief of symptoms. Women who do not obtain adequate relief of symptoms may try starting NSAIDs 1 or 2 days prior to expected menses. NSAIDs should be used for 3 cycles before being declared a treatment failure.​If symptoms are not relieved or if pain becomes worse, refer the patient to an appropriate health-care professional for further assessment.

In terms of safety, NSAIDs have higher overall rates of adverse events (combined GI disturbance, CNS effects and hypersensitivity reactions) compared with placebo. When these events are analyzed separately, only CNS adverse effects have been shown to be statistically significant. This finding is based predominantly on 2 trials using indomethacin and naproxen.​ Safety comparisons among NSAIDs do not indicate the superiority of any agent in this patient population.​

NSAIDs have well-documented drug interactions and contraindications which may not be relevant with occasional, short-term use of these agents. In dysmenorrhea, use is generally limited to 3 days; however, the risks may outweigh the benefits and professional judgment must be used.

In several studies, neither acetaminophen nor ASA was better in providing pain relief than placebo.​ Two trials have shown ASA to be inferior to indomethacin and fenoprofen in terms of pain relief.​Caution is advised regarding the use of ASA in adolescents or young adults because of the possible association with Reye syndrome when ASA is used for conditions such as influenza or varicella. Three trials comparing acetaminophen with NSAIDs indicate that NSAIDs provide superior pain relief in dysmenorrhea.​ Acetaminophen may have value as additive therapy to NSAIDs and in women with intolerance or contraindications to NSAIDs.​

Hormonal Contraceptives

If NSAIDs are contraindicated, if they fail or if birth control is also required, a combined oral contraceptive (COC) is often used to treat dysmenorrhea. COCs relieve dysmenorrhea symptoms by reducing the amount of prostaglandins in menstrual fluid (because they reduce the actual amount of fluid) and by inhibiting ovulation (dysmenorrhea occurs only in ovulatory cycles).​COCs are up to 90% effective in relieving dysmenorrhea symptoms.​This evidence is garnered from older formulations of medium- to high-dose estrogens (50–150 µg ethinyl estradiol) plus first- and second-generation progestogens (norgestrel, levonorgestrel or norethindrone). There are insufficient data on low-dose estrogens (≤35 µg ethinyl estradiol) plus first-, second- or third-generation agents (desogestrel, gestodene) or newer progestogens (drospirenone) to suggest they are as effective as the older formulations.​However, due to safety concerns, low-dose estrogen preparations (≤35 µg ethinyl estradiol) are currently used. Formulations containing ≥50 µg ethinyl estradiol are no longer available in Canada. Safety data for use of COCs in this specific population (women with dysmenorrhea) are lacking.​

According to one randomized, double-blind, controlled trial, continuous COC regimens (3 months) do not appear to offer any benefit beyond cyclic 28-day regimens.​ While a difference in efficacy between continuous and cyclic regimens may exist, the evidence is weak.​

Comparative efficacy of NSAIDs versus COCs for treating dysmenorrhea is unknown.​

The combination of a COC and an NSAID may also be beneficial. About 10% of women do not respond to treatment with NSAIDs, COCs or both.​

Levonorgestrel-containing intrauterine systems (IUS) and oral and parenteral progestogens may have some benefit in dysmenorrhea.​However, larger-scale confirmatory trials are required before use can be recommended.