Stephen R. Wells MD

While society focuses on the emotional aspects of PMS, the vast majority of women suffering from this condition can vouch for the significant physical changes that occur as well. Twenty to forty percent of women are affected, and 2.5% to 5% report a significant impact on their work. Most women, however, seem to think “It is normal for me” and do not seek medical advice.

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The physical symptoms associated with premenstrual syndrome include bloating, breast tenderness, acne, food craving, swelling, headache, and gastrointestinal upset. The emotional symptoms include fatigue, irritability, labile mood with alternating sadness and anger, depression, over-sensitivity, crying spells, social withdrawal, forgetfulness, insomnia, and difficulty concentrating.

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The cause of PMS is unknown, which accounts for the difficulty in trying to find a standardized effective therapy. Some medical studies initially suggested an altered luteal phase estrogen-to-progesterone ratio, although subsequent studies were not able to reproduce these results. These ratios, normal and otherwise, were found to be the same for women who suffered from PMS as those who did not. Rarely, an underlying cause of SEVERE PMS may be related to undiagnosed psychiatric conditions, such as affective mood disorder, anxiety, and personality disturbances. External factors such as marital, family, and work stress commonly escalate the emotional aspects of PMS.

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One of the most helpful factors in establishing a diagnosis of PMS is reviewing a “symptom calendar” that clearly demonstrates a true cyclic change in symptoms and their intensity. Women should be relatively symptom-free from the fourth day of their cycle (4th day of bleeding) to the time of ovulation (usually day 14 of their cycle). After ovulation, they should experience a consistent increase in symptoms.

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25% percent of women who seek medical attention for this condition, however, will report continuous symptoms.

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DIAGNOSTIC WORKUP

1. A careful review of the symptom diary.

2. Blood tests to assess thyroid function and a day-3 follicle stimulating hormone level in women closer to the menopausal time period.

3. Consideration of a psychiatric referral in patients with continuous severe symptoms to rule out other more serious and treatable conditions.

 

TREATMENT

In the following section, we will provide a more critical explanation of therapies and medications used to treat PMS.

1. The following are more standardized medical therapies for the treatment of PMS.

2. Vitamin B6. Dosages up to 200 mg per day have been prescribed for many years. Although some studies have shown that vitamin B6 is effective in reducing a certain percentage of symptoms, other studies have not been able to confirm these results. Women must be careful about taking high-dose vitamin B6, as we do know that permanent sensory neuropathy has been reported in women who take in excess of 1000 mg per day. There have been over ten, randomized, double-blind studies (this is the most reliable type of study) done related to vitamin B6 on PMS. One third of the trials reported positive results, one third negative, and one third ambiguous results. One of the largest multi-center trials done with over 200 patients showed that B6 was no more effective than placebo.

3. Dietary changes. These are commonly recommended in lay literature. There is no evidence, however, that changes in diet would change symptoms related to the menstrual cycle. The elimination of certain food products, such as caffeine and chocolate, for women bothered with significant premenstrual breast tenderness is based largely on uncontrolled studies.

4. Exercise. Regular aerobic exercise has been reported to reduce symptoms. Studies to prove this theory have not been done using a control group, however, and, as a result, they have not been able to show a definitive benefit. Therefore, we would have to say that exercise is not conclusively an effective therapy for PMS and does not appear to cause milder symptomatology. Anecdotally, however, I would still recommend exercise as a non-medical therapy for PMS (and a whole host of other health problems).

5. Vaginal progesterone suppositories. This used to be the most widely use medical treatment. Most studies in the literature have found it to be no more effective than placebo (sugar pill or, in this case, sugar suppository). Because it can cause irregular bleeding and is not effective, it is no longer used.

   1. Oral contraceptives. Many double-blind, placebo-controlled studies have been performed, showing that birth control pills play a role in physical symptoms better than emotional symptoms of PMS. The benefit is modest at best. In my experience, OCPs work okay, but not great.

   2. Alprazolam. Several double-blind, placebo-controlled, randomized, crossover studies (the absolute gold standard in medical studies) showed mixed results. The advantage of this medication is that it is effective in alleviating symptoms of depression and anxiety that may occur concurrently with other PMS symptoms. The disadvantage is that it can lead to dependence, and discontinuing the medication requires tapering. In addition, many women taking alprazolam are bothered by the drowsiness that occurs with it. Although the standard effective dos-age is unknown, most clinicians prescribe alprazolam at anywhere from 0.7 to 2.25 mg daily in divided doses.

   3. Prozac. Several double-blind, randomized, placebo-controlled, crossover trials have been performed, and all of them have found Prozac to be extremely effective. The advantage is that it is well tolerated in a single daily dose and produces a significant decrease in psychic and behavioral symptoms. The only disadvantages are that it is less effective in controlling physical symptoms and there is a social stigma associated to taking Prozac. Most clinicians prescribe Prozac at 20 mg daily, and some administer the drug continuously, while others treat for several weeks of the month. Prozac, which prevents the re-uptake and destruction of serotonin, has other competitors. Sertraline hydrochlorothiazide (Zoloft) may also be used; although not studied in controlled trials, it may be just as effective because the method of action is the same.

   4. Spironolactone. Several double-blind, randomized, placebo-controlled trials have been performed showing mixed results. The advantage of spironolactone is that it alleviates bloating and other physical aspects of PMS. In addition, it may improve mood, although not too effectively. It is an oral medication taken once or twice a day. It is non-addictive and usually administered at lower dosages.

   5. Gonadotropin-releasing hormone agonist. There are several, small, double-blind, randomized, placebo-controlled, crossover studies showing significant improvement in symptoms. This is an injectable medication that is given once monthly. It produces a pseudo-menopause by basically shutting down the ovaries. It is expensive, and there is the risk of developing osteoporosis with prolonged use. It also causes hypo-estrogenic symptoms, including hot flashes, vaginal dryness, and sometimes joint pain, and is usually given for only short periods of time. In addition, estrogen and progesterone can be given in very low doses as an “add-back” regimen to retard development of osteoporosis and hypo-estrogenic symptoms. Utilizing the add-back regimen, this form of therapy carries with it much less risk.

   6. Alternative medications. Multiple double blind placebo controlled studies have been performed with herbal remedies. Most have shown no benefit over placebo. In my experience, women who choose herbs do not stay on them for long (placebo effect).

 

CONCLUSIONS

For the treatment of premenstrual syndrome to be successful, it is important to accurately diagnose the condition based on a symptom calendar. It is also important to exclude any medical or psychiatric disorders and confirm the cyclicity by a prospective symptom calendar.

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We feel that women who are diagnosed with PMS should first attempt to make lifestyle changes. This would include exercise and stress reduction. Should these lifestyle changes not have any impact on PMS, then a therapy can be tailored based on a woman’s symptoms. For those who have more physical disturbances, diuretic therapy with spironolactone is useful. For those who have more emotional mood problems, birth control pills, Prozac, and, for those patients who can be monitored reliably, alprazolam can be used. I usually recommend Prozac, despite its stigmata. I have found that patients who try it continue to use it over the long haul. Why? Because it works.