Treatment of Premenstrual Syndrome and Premenstrual Dysphoric Disorder

TREATMENT

The prospective charting of symptoms not only documents the cyclic or noncyclical nature of the patient’s symptoms, but also allows her to play a key role in the diagnostic and management team. This will allow her to regain some con-trol of her symptoms. For some women, providing a diag-nostic label helps relieve the fear that they are “going crazy.” Often a patient’s symptoms become more bearable as she gains insight. The symptom calendar is usually con-tinued during the treatment phase to monitor the effec-tiveness of treatment and to suggest the need for further focused therapy.

Nonpharmacologic Treatment

Diet recommendations emphasize eating fresh rather than processed foods. The patient is encouraged to eat more fruits and vegetables and minimize refined sugars and fats. Minimizing salt intake may help with bloating, and eliminat-ing caffeine and alcohol from the diet can reduce nervous-ness and anxiety. None of these therapies have shown statistically significant improvements in PMS and PMDD, but they are reasonable, benign, a good part of general health improvement, and in some studies have demon-strated trends towards improvement. Clearly these interven-tions yield low risks and are generally healthful behaviors.

Lifestyle interventions that have demonstrated significant improvement in symptoms include aerobic exercise and calcium carbonate and magnesium supplementation. Aerobic exercise,as opposed to static (e.g., weightlifting) exercise, has been found to be helpful in some patients, possibly by increasing endogenous production of endorphins. Calcium decreases water retention, food cravings, pain, and negative affect, compared with placebo.

Other interventions have been studied, but demon-strate conflicting results. These include vitamins E and D or chaste-tree berry extract, as well as relaxation therapy, cognitive therapy, and light therapy. 

Many of these thera-pies have no untoward side effects, and can be considered for certain patients. Studies have shown that B6 supple-mentation has limited clinical benefit. Patients should be cautioned that dosages in excess of 100 mg/d may cause medical harm, including peripheral neuropathy. Studies of evening primrose oil demonstrate no benefit. Alternative therapies include meditation, aromatherapy, reflexology, acupuncture, acupressure, and yoga. Further research is warranted in these areas. 

Pharmacologic Treatment

In addition to lifestyle changes, behavioral therapies, and dietary supplementation, some pharmacologic agents have been shown to provide symptomatic relief. Nonsteroidal anti-inflammatoryagents (NSAIDs) have been found in controlled trialsto be useful in PMS patients with dysmenorrhea, breast pain, and leg edema, but not useful in treating other aspects of PMS. This effect is possibly related to pros-taglandin production in various sites in the body. Spiro-nolactone decreases bloating, but does not relieve other symptoms.

Because the underlying mechanism appears to be nor-mal hormone fluctuations triggering an abnormal sero-tonin response, it would seem that medications to induce anovulation should be beneficial in the treatment of PMS/ PMDD. The research on PMS/PMDD has been fraught withmultiple challenges because the strict criteria for diagnosis of PMS/PMDD have only recently been established and standard-ized, many previous studies suffered from poor methodology, and the placebo effect (30% to 70%) in patients with PMS/PMDD is significant. Because symptoms are associated with ovula-tory cycles, suppressing ovulation is beneficial for some patients with PMS and can be accomplished by using oral contraceptives, danazol, or gonadotropin-releasing hor-mone (GnRH) agonists. Oral contraceptives are a logicalfirst choice for patients who also require contraception. Some patients, however, find that their symptoms worsen when taking oral contraceptives.

As an overall clinical approach, treatments should be employed in increasing orders of complexity.

Using this principle, in most cases, the therapies should be used in the following order:

Step 1. Supportive therapy, complex carbohydrate diet,nutritional supplements (calcium, magnesium, vitamin E), spironolactone

Step 2. Selective serotonin reuptake inhibitors (SSRIs), withfluoxetine or sertraline as the initial choice; for women who do not respond, consider an anxiolytic for specific symptoms

Step 3. Hormonal ovulation suppression (oral contracep-tives or GnRH agonists)

The medical treatment of PMDD differs from that of PMS. Ovulation suppression does not seem to help patients with PMDD. Though many medications have been studied, only four are U.S. Food and Drug Administration (FDA)-approved for the treatment of PMDD: fluoxetine, sertraline, paroxetine controlled-release, and drospirenone/ethinyl estradiol.

In patients who have been diagnosed with PMDD using the strict criteria, the gold standard of treatment is the SSRIs.

In a Cochrane Data Base Review, 15 randomized placebo-controlled trials demonstrated benefit with SSRIs. The combination of drospirenone and ethinyl estradiol is the only oral contraceptive regimen that has demonstrated benefit and is the newest therapeutic choice for the treat-ment of PMDD. SSRIs are effective when dosed contin-uously (daily dosage); or dosed intermittently (taken only during the luteal phase [the 14 days prior to onset of menses]). Patients often report improvement with their first cycle of use, lending credence to the idea that the pathophysiology of PMDD is different from that of major depressive disorder, in which treatment can take weeks to demonstrate improvement. Side effects of SSRIs include gastrointestinal upset, insomnia, sexual dysfunc-tion, weight gain, anxiety, hot flushes, and nervousness.

The use of danazol and GnRH agonists has been demon-strated to be beneficial in short-term studies, but long-term effects of such drugs for PMS/PMDD have not been fully evaluated, and these medications are associated with signifi-cant, often prohibitive, side effects. The use of either consti-tutes a “medical oophorectomy” and may be used as a trial before surgical oophorectomy is undertaken. Oopho-rectomy should be reserved for those severely affected patients who meet strict diagnostic criteria and who do not respond to any potentially effective therapy other than GnRH agonists.