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Premenstrual Syndrome: Systematic Diagnosis and Individualized Therapy

Scott Ransom, DO, MBA; Julie Moldenhauer, MD


In Brief: Premenstrual syndrome, or PMS, typically involves physical symptoms like bloating, headache, and breast tenderness, along with psychological and behavioral changes like irritability, depression, and fatigue. Other conditions can mimic PMS, so it's important to rule out look-alikes such as contraceptive side effects, dysmenorrhea, and substance abuse. Moderate exercise and a healthy diet may alleviate symptoms for some patients. Others may require symptom-specific measures, hormonal therapy, psychotropic drugs, or, for recalcitrant cases, ovulation suppression.

Women of all athletic abilities can suffer from premenstrual syndrome (PMS), which in some cases can be debilitating. It is imperative that the primary care physician undertake a thorough, stepwise evaluation to rule out other conditions and know effective options for targeted treatment.

Signs and Symptoms

PMS is a combination of distressing physical, psychological, and behavioral changes during the luteal phase of the menstrual cycle. The core physical symptoms include bloating, headache, breast tenderness, and, less commonly, appetite changes, gastrointestinal upset, vasomotor flushing, heart palpitations, and dizziness. Psychological and behavioral changes often include irritability, depression, fatigue, labile mood, concentration difficulties, and forgetfulness. A physically active woman who has significant PMS symptoms may be less motivated to exercise or may show reduced athletic performance.

A key to diagnosis is that the symptoms occur during the luteal phase of the menstrual cycle (days 15 to 28). In addition, the appropriate diagnosis of PMS requires a combination of one psychological or behavioral change and one physical symptom consistently during the luteal phase (1). Because more than 150 behavioral, physical, and psychological symptoms are associated with PMS (2), widely accepted diagnostic criteria have been developed (table 1: not shown).

Fine-Tuning the Differential

The appropriate diagnosis of PMS is vital for optimal outcome. Although many women come to the physician's office with individual symptoms of PMS, a systematic inquiry concerning signs and symptoms is crucial before treatment decisions can be made.

The first visit should focus on a careful history and physical examination to develop a complete differential diagnosis. The patient should receive instructions on how to chart her symptoms daily for her next two full menstrual cycles (figure 1: not shown). This usually entails tracking three to five of her most severe symptoms with daily recording of their absence or presence, severity, and menstrual timing. The first visit should also include other testing as needed to aid in the evaluation of other possible conditions in the differential. The patient should return after charting two complete cycles.

When evaluating the patient's symptom chart, it may prove useful to consider premenstrual, menstrual, and postmenstrual phases. Charting consistent with PMS will show symptoms at or after ovulation only, resolving within 4 days after the onset of menses. The follicular phase will be relatively symptom free.

Many patients who report PMS will have another condition that can account for their symptoms (table 2). Recording of symptoms will show that many patients experience no symptom-free interval or have non-menstrually related exacerbation of symptoms. These findings will divert the diagnosis away from PMS.

Table 2. Conditions Commonly Confused With Premenstrual Syndrome

Contraceptive side effects
Other drug side effects
Eating disorders
Substance abuse
Manic depression
Other psychiatric disorders

Hormonal contraceptive side effects, dysmenorrhea, eating disorders, substance abuse, and other medical conditions are commonly confused with PMS (3). Up to 60% of women seeking treatment for PMS have a diagnosed psychiatric disorder, with the most common being depression and adjustment disorders (4). Premenstrual worsening of psychiatric symptoms can make the diagnosis confusing, but PMS can be diagnosed only if the patient has an asymptomatic week during the follicular phase.

The Beck Depression Inventory may help in the diagnosis of depressive symptoms in PMS. Having the patient complete this test during the midfollicular and again in the late luteal phase helps distinguish those suffering from chronic depression from those who have PMS-associated depression.

The clinician must be aware of cyclic recurrence of other medical disorders, such as migraines, herpes, convulsive disorders, irritable bowel syndrome, and hypothyroidism, in which symptoms most often recur in the late luteal or early menstrual phase (5). A more complex pattern will be that of PMS with an additional disorder, which shows symptoms throughout the menstrual cycle but with different PMS symptoms in the late luteal phase. Non-PMS symptoms that are present in all three phases but more severe in a particular phase generally represent a cyclic exacerbation of a chronic disorder. Detailed charting and evaluation will help determine if such symptoms are consistent with PMS.

Diet and Exercise Steps

The first therapeutic options for PMS are typically self-help techniques like healthy nutrition, dietary supplements, increased exercise, and stress reduction. These measures should be emphasized if the patient's symptoms are not severe and last less than 1 week. Detailed discussions with the patient are vital for these nonpharmacologic options to succeed.

Diet and supplements. While no foods have been specifically shown to be beneficial in treating PMS, an overall healthy diet may reduce many symptoms.

Vitamin and mineral supplements have been suggested to ameliorate PMS symptoms. Calcium (1,000 mg elemental daily) and magnesium have been shown to improve mood and to reduce pain and fluid retention for patients experiencing PMS, though the mechanism of action is unknown (6,7). Extensive research has shown that vitamin B6, however, has inconsistent efficacy in PMS treatment, with possible neurotoxicity as a side effect (8). Calcium and magnesium are cofactors in neurotransmitter synthesis, which suggests a possible association between PMS symptoms and serotonin deficiency (5-8).

Exercise and other stress reducers. Besides improving cardiovascular status and general health, regular, moderate exercise appears to be the best nonpharmacologic agent to combat the symptoms of PMS (table 3) (9). Many anecdotal reports link exercise with a reduction or alleviation of PMS symptoms. Women who exercise seem to have fewer luteal-phase symptoms than sedentary individuals (9).

Table 3. Potential Benefits of Moderate Aerobic Exercise for Women Who Have Premenstrual Syndrome

Fewer luteal-phase symptoms
Decreased dysmenorrhea
Reduced stress
Decreased symptoms of impaired concentration
Reduced mood alterations
No pharmacologic side effects

Aerobic activity decreases PMS symptoms more effectively than nonaerobic activity (10). Moderately intense aerobic activity seems to effect optimum reduction of symptoms. Good aerobic activities include walking, jogging, biking, swimming, rowing, and dancing.

Exercise has been found helpful in ameliorating mood alterations, without the untoward side effects of medications. Stress reduction seems to be the primary mode of action. Women who have a trained cardiovascular system have been found to have a more appropriate heart rate response to the stress of PMS than sedentary women (11,12). Studies (11,12) have shown that women who participate in regular exercise have decreased symptoms of impaired concentration, negative affect, behavior change, and pain. However, the positive effects of exercise on mood are reduced for those who train intensely (13).

Relaxation techniques have also been shown to reduce the mood symptoms of PMS (14). Relaxation techniques are particularly helpful for women who are able to identify their stressors.

Relief of Specific Symptoms

Although no experimental evidence has shown that women who have PMS actually retain fluid, the sensation of bloating can often be treated. Reduction in dietary salt should be encouraged. If a diuretic is needed, spironolactone is the drug of choice because it is a potassium-sparing diuretic with less risk of inducing dependence than other diuretics (15). The physician must recommend diuretics cautiously; abuse can cause edema because decreased sodium stimulates the renin-angiotensin-aldosterone system to ultimately cause sodium retention. Patients should initiate diuretic use when the sensation of fluid retention begins and continue the drug until the onset of menses, when symptoms usually resolve.

Mastalgia can be conservatively treated with a support bra and reduced caffeine intake. For unresponsive, severe symptoms, nonsteroidal anti-inflammatory drugs (NSAIDs), bromocriptine mesylate, tamoxifen citrate, and danazol have all been shown to reduce breast pain (16-18).

Patients who experience insomnia, waking in the middle of the night, or daytime fatigue should try a regular sleep pattern and avoid physical activity and food just before bedtime, as well as alcohol. If needed, a tricyclic antidepressant taken 1 to 2 hours before bedtime may help (9).

Dysmenorrhea associated with PMS may be effectively treated with NSAIDs and/or oral contraceptives (OCPs). Physicians may need to try various NSAIDs until one relieves the patient's symptoms with tolerable side effects. If dysmenorrhea does not resolve with medical therapy, gynecologic consultation should be considered to evaluate for such problems as endometriosis, fibroid uterus, ovarian cyst, adenomyosis, and other pelvic disorders.

Migraines may be considered a symptom of PMS only if they occur in the late luteal or early menstrual phase and if other causes are ruled out. NSAIDs can be used as prophylactic or abortive therapy for patients experiencing monthly symptoms (19,20). If NSAIDs fail, beta-adrenergic blockers, such as propranolol hydrochloride in daily divided doses, or low-dose tricyclic antidepressants are often effective. Hormonal therapies that involve danazol or gonadotropin-releasing hormone (GNRH) agonists have also been suggested if first-line treatment proves ineffective (9).

Hormonal Therapy

If the most severe symptoms cannot be treated adequately with the therapies mentioned above, hormonal therapy should be considered. Treatment, however, must be individualized (19).

Younger women can be treated with oral contraceptives after consideration of dysmenorrhea and the need for contraception. With the exception of dysmenorrhea, however, oral contraceptive therapeutic effectiveness is controversial in PMS. The effect of oral contraceptives on PMS is very poorly defined in the literature, since few studies have specifically addressed this treatment, especially with the more current formulations. The studies that have been completed show very little if any effect on PMS symptoms with oral contraceptive use. Most PMS symptoms are not improved with oral contraceptives, and claims of their effectiveness in PMS should be questioned.

Perimenopausal women who have PMS symptoms and associated irregular menses should have their level of follicle-stimulating hormone measured to rule out menopause. Because treatment in this age-group will likely be short, it is often acceptable to go directly to ovulation suppression with daily medroxyprogesterone acetate. If menopause is diagnosed, standard combined estrogen-progestin hormone replacement therapy should be used.

PMS has never been proven to be associated with a progesterone deficiency, and many conflicting studies have been presented for the use of progesterone in the treatment of PMS (21). The use of natural progesterone has yielded a positive response for some clinicians (22). Some feel that the controversy over progesterone's efficacy is due to misunderstanding of the differences between natural progesterone and synthetic progestogens as well as a lack of adequate double-blind studies supporting the efficacy of natural progesterones (23,24). Thus, although the vast majority of literature does not support prescribing progesterone for PMS, the drug has its advocates.

Psychiatric Drugs

For women who have PMS and significant mood lability, irritability, anxiety, or depression, psychotropic medications may be an option. Serotonin uptake inhibitors, such as fluoxetine hydrochloride and clomipramine hydrochloride, have been found to improve premenstrual psychological symptoms (25,26).

Naltrexone hydrochloride, a narcotic antagonist, and clonidine hydrochloride, a central alpha-2-adrenergic presynaptic autoreceptor agonist, have both shown improvement over placebo in treating premenstrual psychiatric symptoms (27-29). Their mechanism may be modulation of beta-endorphin levels. Alprazolam, a relatively new triazolobenzodiazepine, is a shorter-acting and potent anxiolytic that improves irritability, mood lability, anxiety, fatigue, and depression (30). Antidepressants, including nortriptyline hydrochloride, clomipramine, and fluoxetine, can help alleviate depressive symptoms associated with PMS (31-33).

Other Therapeutic Options

Ovulation suppression is usually warranted only for cases refractory to one or more nonsuppressive therapies or for those that involve severe, disruptive symptoms. Methods of ovulation suppression may include oral medroxyprogesterone acetate, danazol (200 to 400 mg/day) (34), and GNRH agonists. Danazol and GNRH agonists appear to be the most effective of the hormonal suppressive therapies, but most patients are better served with GNRH agonists because of the bothersome androgenic side effects of danazol.

Oophorectomy is rarely indicated for PMS, and only after strict criteria are met (35). The patient's symptoms should have failed to resolve after all therapy except ovulation suppression by danazol or a GNRH agonist. The response to ovulation suppression must be the complete resolution of symptoms for a minimum of 4 to 6 months. If oophorectomy is solely for treating severe PMS, hysterectomy should also be performed. Otherwise, estrogen replacement therapy would also require the added risks and expense of cyclic progesterone to prevent endometrial carcinoma. With severe PMS, progestin therapy can create PMS-like symptoms and should be avoided.

Effective Follow-Up

Appropriate follow-up is just as important as treatment choice. Symptom recording, although exacting, must continue as part of treatment. If drug efficacy is established by symptom recording, such recording should continue at least every other cycle. If a decrease in effectiveness or any side effects are revealed, early adjustments can be made.

Because the first cycle or two may feature a placebo effect or a flare-up of symptoms unrelated to therapy, it's wise not to alter therapy because of one or two symptomatic cycles. If initial therapy proves effective over the first three cycles, the patient then can be re-evaluated less frequently, perhaps every 3 to 6 months.

Regardless of the effectiveness of treatment, if the patient initially had more severe symptoms—especially psychological ones—more frequent visits are warranted until the diagnosis is clearly established and effective treatment is instituted. Thus, individualized follow-up must be based on symptom profile, drugs prescribed, and the patient's requests.


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Dr Ransom is an assistant professor and director of Community Programs and Health Effectiveness in the Department of Obstetrics and Gynecology at Wayne State University School of Medicine in Detroit and the Detroit Medical Center. He is a fellow of the American College of Obstetricians and Gynecologists and of the American College of Surgeons. Dr Moldenhauer is a resident in obstetrics and gynecology at Wayne State University and Hutzel Hospital in Detroit. Address correspondence to Scott Ransom, DO, MBA, Dept of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Hospital, 4707 St Antoine Blvd, Detroit, MI 48201.



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