Premenstrual Syndrome

Essentials of Diagnosis • Symptoms include mood symptoms (irritability, mood swings, depression, anxiety), physical symptoms (bloating, breast tenderness, insomnia, fatigue, hot flushes, appetite changes), and cognitive changes (confusion and poor concentration). • Symptoms must occur in the second half of the menstrual cycle (luteal phase). • There must be a symptom-free period of at least 7 days in the first half of the cycle. • Symptoms must occur in at least two consecutive cycles. • Symptoms must be severe enough to require medical advice or treatment. General Considerations Premenstrual syndrome (PMS) is a psychoneuroendocrine disorder with biologic, psychologic, and social parameters. It is both difficult to define adequately and quite controversial. One major difficulty in detailing whether PMS is a disease or a description of physiologic changes is its extraordinary prevalence. Up to 75% of women experience some recurrent PMS symptoms; 20–40% are mentally or physically incapacitated to some degree, and 5% experience severe distress. The highest incidence occurs in women in their late 20s to early 30s. PMS is rarely encountered in adolescents and resolves after menopause. Evidence suggests that women who have suffered with PMS and premenstrual dysphoric disorder are more likely to suffer from perimenopausal symptoms. The symptoms of PMS may include headache, breast tenderness, pelvic pain, bloating, and premenstrual tension. More severe symptoms include irritability, dysphoria, and mood lability. When these symptoms disrupt daily functioning, they are clustered under the name premenstrual dysphoric disorder (PMDD). Other symptoms commonly included in PMS are abdominal discomfort, clumsiness, lack of energy, sleep changes, and mood swings. Behavioral changes include social withdrawal, altered daily activities, marked change in appetite, increased crying, and changes in sexual desire. In all, more than 150 symptoms have been related to PMS. Thus the symptom complex of PMS has not been clearly defined. Pathogenesis The etiology of the symptom complex of PMS is not known, although several theories have been proposed, including estrogen–progesterone imbalance, excess aldosterone, hypoglycemia, hyperprolactinemia, and psychogenic factors. A hormonal imbalance previously was thought to be related to the clinical manifestations of PMS/PMDD, but in the most recent consensus, physiologic ovarian function is believed to be the trigger. This is supported by the efficacy of ovarian cyclicity suppression, either medically or surgically, in eliminating premenstrual complaints. Further research has shown that serotonin (5-hydroxytryptamine [5-HT]), a neurotransmitter, is important in the pathogenesis of PMS/PMDD. Both estrogen and progesterone have been shown to influence the activity of serotonin centrally. Many of the symptoms of other mood disorders resembling the features of PMS/PMDD have been associated with serotonergic dysfunction. Diagnosis No objective screening or diagnostic tests for PMS and PMDD are available; thus special attention must be paid to the patient's medical history. Certain medical conditions (eg, thyroid disease and anemia) with symptoms that can mimic those of PMS/PMDD must be ruled out. The patient is instructed to chart her symptoms for at least 2 symptomatic cycles. The classic criteria for PMS require that the patient have symptoms in the luteal phase and a symptom-free period of at least 7 days in the first half of the cycle for a minimum of 2 consecutive symptomatic cycles. To meet the criteria for PMDD, in addition to the criteria for PMS, she must have a chief complaint of at least 1 of the following: irritability, tension, dysphoria, or mood lability; and 5 of 11 of the following: depressed mood, anxiety, affective lability, irritability, decreased interest in daily activities, concentration difficulties, lack of energy, change in appetite or food cravings, sleep disturbances, feeling overwhelmed, or physical symptoms (eg, breast tenderness, bloating). Clinical Findings A careful history and physical examination are most important to exclude organic causes of PMS localized to the reproductive, urinary, or gastrointestinal tracts. Most patients readily describe their symptoms, but careful questioning may be needed with some patients who may be reluctant to do so. Although it is important not to lead a patient to exaggerate her concerns, it is equally important not to minimize them. Symptoms of PMS may be specific, well localized, and recurrent. They may be exacerbated by emotional stress. Migrainelike headaches may occur, often preceded by visual scotomas and vomiting. Symptomatology varies among patients but often is consistent in the same patient. A psychiatric history should be obtained, with special attention paid to a personal history of psychiatric problems or a family history of affective disorders. A mental status evaluation of affect, thinking, and behavior should be performed and recorded. A prospective diary correlating symptoms, daily activities, and menstrual flow can be useful to document changes and to encourage patient participation in her care. If underlying psychiatric illness is suspected, a psychiatric evaluation is indicated. The most common associated psychiatric illness is depression, which generally responds to antidepressant drugs and psychotherapy. Recall that psychiatric illnesses have premenstrual exacerbations, so medications should be altered accordingly. Treatment Treatment of PMS/PMDD depends on the severity of the symptoms. For some women, changes in eating habits—limiting caffeine, alcohol, tobacco, and chocolate intake, and eating small, frequent meals high in complex carbohydrates—may be sufficient. Decreasing sodium intake may alleviate edema. Stress management, cognitive behavioral therapy, and aerobic exercise have all been shown to improve symptoms. Low-risk pharmacologic interventions that may be effective include calcium carbonate (1000–1200 mg/d) for bloating, food cravings, and pain; magnesium (200–360 mg/day) for water retention; vitamin B6 (note that prolonged use of 200 mg/d may cause peripheral neurotoxicity) and vitamin E; nonsteroidal anti-inflammatory drugs (NSAIDs); spironolactone for cyclic edema; and bromocriptine for mastalgia. Herbal preparations have been proposed. St. John's wort has potential given its selective serotonin reuptake inhibitor (SSRI)-like effects but should be used with caution given its enzyme-inducing property on cytochrome P450. Chaste berry fruit (Vitex agnus-castus) 20 mg/day has been shown to be more effective than placebo and has minimal side effects but is not as effective as fluoxetine. For symptoms of severe PMS and PMDD, further pharmacologic intervention may be necessary. Psychotropic medications that are effective include SSRIs, desipramine, and L-tryptophan. SSRIs have minimal side effects and provide symptom improvement in more than 60% of patients studied. Treatment should be given 14 days prior to the onset of menstruation and continued through the end of the cycle. Anxiolytics such as alprazolam and buspirone also have been shown to be efficacious, but their side effects and potential for dependence must be seriously considered. Hormonal interventions have been shown to be effective. Use of gonadotropin-releasing hormone (GnRH) agonists leads to a temporary "medical menopause" and an improvement in symptoms. Their limitations lie in a hypoestrogenic state and a risk for osteoporosis, although "add-back" therapy with estrogen and progesterone may obviate these problems. Danazol may improve mastalgia. Finally, bilateral oophorectomy is a definitive surgical treatment option; again, estrogen replacement would be recommended. Use of oral contraceptives has been suggested because they suppress ovulation. However, studies have found little difference between women taking a low-dose birth control pill and women who do not take pills, and oral contraceptives currently are not recommended for treatment of PMS/PMDD.