Premenstrual syndrome (PMS) affects millions of women during their reproductive years. The disorder is characterized by the cyclic recurrence of symptoms during the luteal phase of the menstrual cycle (Table 1). (1-3) Symptoms typically begin between the ages of 25 and 35 years. Women who have severe affective symptoms may also meet criteria for premenstrual dysphoric disorder (PMDD). In both PMS and PMDD, symptoms diminish rapidly with the onset of menses.
Up to 85 percent of menstruating women report having one or more premenstrual symptoms, and 2 to 10 percent report disabling, incapacitating symptoms. (4,5) More than 200 symptoms have been associated with PMS, but irritability, tension, and dysphoria are the most prominent and consistently described. (5)
The management of PMS is often frustrating for both patients and physicians. Clinical outcomes can be expected to improve as a result of recent consensus on diagnostic criteria for PMS and PMDD, data from improved clinical trials, and the availability of evidence-based clinical guidelines.
Etiology
The etiology of PMS remains unknown and may be complex and multifactorial. The role of ovarian hormones is unclear, but symptoms often improve when ovulation is suppressed. (6) Changes in hormone levels may influence centrally acting neurotransmitters such as serotonin, (1) but circulating sex hormone levels are typically normal in women with PMS. Some evidence suggests that the disorder is related to enhanced sensitivity to progesterone in women with underlying serotonin deficiency. (1,4,7) This mechanism may not explain all cases, because some patients do not respond to treatment with selective serotonin reuptake inhibitors (SSRIs). (8) Deficiencies in prostaglandins, related to an inability to convert linoleic acid to prostaglandin precursors, may be involved in PMS.2,9 Genetic factors also seem to play a role, as the concordance rate is two times higher in monozygotic twins than in dizygotic twins. (10)
Diagnosis
The American College of Obstetrics and Gynecology (ACOG) recommends the PMS diagnostic criteria developed by the University of California at San Diego and the National Institute of Mental Health (Table 2). (4,7) In women with severe dysphoric symptoms and significant dysfunction, research criteria can be used to establish the diagnosis of PMDD (Table 3). (11) All diagnostic criteria emphasize the periodicity and severity of symptoms.
PMS and PMDD can only be diagnosed after a variety of physical and psychiatric disorders have been excluded (Table 4). (3,4) PMS also must be distinguished from simple premenstrual symptoms (e.g., bloating, breast tenderness) that do not interfere with daily functioning and are characteristic of normal ovulatory cycles (7) (Figure 1). The three key elements of the diagnosis are symptoms consistent with PMS, consistent occurrence of symptoms only during the luteal phase of the menstrual cycle, and negative impact of symptoms on function and lifestyle. (4)
[FIGURE 1 OMITTED]
When PMS or PMDD is suspected, patients should be instructed to keep a premenstrual daily symptom diary for several consecutive months so that cycle-to-cycle variability can be examined (Figure 2). Based on this diary, many women may be found to have nonluteal symptom patterns. (7) Standardized daily symptom calendars, such as the Calendar of Premenstrual Experiences and the Prospective Record of the Impact and Severity of Menstruation, provide reliable and convenient records. (4,7)
Management
Treatment goals for PMS are to ameliorate or eliminate symptoms, reduce their impact on activities and interpersonal relationships, and minimize adverse effects of treatment. Although numerous treatment strategies are available, few have been adequately evaluated in randomized, controlled trials. Furthermore, research findings can be difficult to apply because of the variability of inclusion criteria and outcome measures in clinical trials, the lack of studies directly comparing treatment modalities, and the high response rate to placebo (25 to 50 percent). (2,3)
Initially, all patients with PMS should be offered nonpharmacologic therapy. (4) Medication should be offered to patients with persistent symptoms of PMS and those who meet criteria for PMDD. Surgical treatment, principally hysterectomy plus bilateral oophorectomy, is controversial because it is irreversible and associated with significant risks. Surgery may be considered in severely affected patients who fail to respond to other therapies and also have significant gynecologic problems for which surgery would be appropriate. (1,4)
NONPHARMACOLOGIC THERAPY
Nonpharmacologic interventions for PMS include patient education, supportive therapy, and behavioral changes. (1,3) Women who have been educated about the biologic basis and prevalence of PMS report an increased sense of control and relief of symptoms. (4)
Although not rigorously evaluated, supportive therapy may be responsible for the high placebo-response rates in clinical trials. Small comparative trials (1,4,12) show some benefit for formal psychologic interventions such as relaxation therapy and cognitive behavioral therapy. Behavioral measures include keeping a symptom diary, getting adequate rest and exercise, and making dietary changes.
The daily symptom diary may help patients identify optimal times for implementing behavioral and other changes to manage symptom exacerbations. Women report that maintaining a symptom diary helps them manage PMS or PMDD. (3,7)
Sleep disturbances, ranging from insomnia to excessive sleep, are common in women with PMS. A structured sleep schedule with consistent sleep and wake times is recommended, especially during the luteal phase. (3)
Dietary restrictions and exercise may also be useful in patients with PMS. (3,7) Sodium restriction has been proposed to minimize bloating, fluid retention, and breast swelling and tenderness. Caffeine restriction is recommended because of the association between caffeine and premenstrual irritability and insomnia. In epidemiologic and short-term prospective studies, (1,4,13,14) women with PMS who practiced aerobic exercise reported fewer symptoms than control subjects.
In one randomized, placebo-controlled crossover trial, (15) chiropractic therapy was associated with a decrease in PMS symptoms. However, this effect was only noted in patients randomized to initially receive chiropractic treatment.
DIETARY SUPPLEMENTATION
Dietary supplements that have been evaluated in women with PMS include vitamins (A, E, and [B.sub.6]), calcium, magnesium, multivitamin/mineral supplements, and evening primrose oil. Because most studies have been small or poorly designed, efficacy needs to be confirmed in large, well-designed clinical trials before evidence-based recommendations can be made.
In nine randomized, controlled clinical trials of vitamin [B.sub.6] as a single supplement or in a multivitamin, improvement of symptoms was reported, but the poor quality of the trials limits their usefulness. (16) [Evidence level B, systematic review of lower quality randomized controlled trials (RCTs)] Vitamin [B.sub.6] should not be routinely recommended for women with PMS. (1,4,16)
Studies of vitamin A do not support its use, but vitamin E supplementation is a recognized treatment for mastalgia. (3,4) In one randomized, controlled trial, the administration of 400 IU per day of vitamin E during the luteal phase was found to improve affective and somatic symptoms in women with PMS. (4) The ACOG (4) recognizes vitamin E as a potential treatment for PMS, because of minimal harm and its potentially beneficial antioxidant effect.
Supplements of calcium carbonate in a dosage of 1,200 mg per day for three menstrual cycles resulted in symptom improvement in 48 percent of women with PMS, compared with 30 percent of placebo-treated women. (17) [Evidence level A, RCT] Magnesium in a dosage of 200 to 400 mg per day has shown minimal benefit in alleviating bloating. (1,4,18) The ACOG (4) recommends calcium supplementation but not magnesium supplementation.
Evening primrose oil, a prostaglandin precursor, has been studied in women with PMS, based on the theory of inadequate levels of prostaglandin [E.sub.1]. A systematic review of placebo-controlled trials of evening primrose oil suggested lack of benefit in PMS, although mild relief was demonstrated in women with breast tenderness. (9) [Evidence level B, systematic review of lower quality RCTs]
PHARMACOLOGIC THERAPY
Nonpharmacologic measures should be monitored at least every three months. If symptoms are not adequately relieved, the addition of pharmacologic treatment should be considered (Table 5). (19,20) Medications are given to treat specific symptoms or alter the menstrual cycle. Treatment should be individualized to target the most troublesome symptoms in each patient.
