PMS: proof or promises?

I was in the library, searching for an article on (what else?) saturated fats, when the headline caught my eye: "Efficacy of Alpha-Tocopherol in the Treatment of the Premenstrual Syndrome."

Could a simple, safe supplement like vitamin E put an end to PMS - those monthly bouts of misery that afflict millions of otherwise normal women, and indirectly, the men and children who have to live or work with them?

I've never had a particularly bad case of PMS. Usually it's only a day or two of feeling irritable and unable to cope. My response to the problem is not exactly high-tech: I try not to cry in public or say anything I'll later regret, and I wait for the day to end.

But what if vitamin E, vitamin B-6, or one of those "PMS Formula" supplements could end all that? I abandoned saturated fats and read on.

Dr. Jekyll/Ms. Hyde. The scientific literature on PMS is a mess. That's because no one is quite sure what it is.

In 1983, investigators at the National Institute of Mental Health (NIMH) agreed that only women who met two criteria should participate in studies on PMS:

* The women had to record their symptoms daily for three months, rather than fill out questionnaires about how they usually feel the week before their menstrual periods.

* For at least two of the three months, they had to report at least a 30-percent change in symptoms between the pre-and post-menstrual weeks of their monthly cycles.

"Only about one-third of the women who seek help from health professionals actually have PMS according to these criteria," says the NIMH's Peter Schmidt.

"The way these women feel, the way they perceive themselves and others and their life activities, undergoes a profound change," says Schmidt. "It's really a Dr. Jekyll/Mr. Hyde phenomenon."

Using the NIMH's criteria, four to seven percent of all women suffer from PMS, says Schmidt. But in response to other surveys, many more women - perhaps 30 to 40 percent - report premenstrual symptoms. There are well over 100, including mood swings, food cravings, temper outbursts, breast tenderness, bloating, and - my husband will love this one - a "tendency to nag."

Like me, these women may not have what the NIMH calls PMS. But they're often the ones taking the PMS supplements, buying the self-help PMS books, and visiting the PMS clinics. I decided to start will studies on this poorly defined group, knowing that their uncertain diagnosis makes the results somewhat questionable.

Folk Remedies? In a recent survey of 630 nursing-school graduates who said they had premenstrual symptoms, one out of four said they had "Changed their diet" to help relieve their discomfort.[1] "The changes recommended most commonly are decreasing the intake of fat, sugar, salt, alcohol, and caffeine," says the study's co-author, Susan Johnson, of the University of Iowa.

But no one's ever tested those changes to see if they help.

Johnson also found that 19 percent of the nurses took vitamins and 42 percent exercised. Studies have tested those remedies, but the evidence, I soon discovered, is rather skimpy.

"E" for "Equivocal." Robert London, director of Reproductive Medicine at North Charles Hospital in Baltimore, was testing vitamin E's ability to alleviate discomfort caused by benign breast lumps (it didn't) when he decided to investigate the vitamin's effects on premenstrual symptoms.

Every day for three menstrual cycles, 22 women took 400 International Units (IU) of vitamin E, while 19 others took an inactive, look-alike placebo.[2] (London didn't use the NIMH's criteria to screen the women, so chances are they had premenstrual symptoms, not the more severe syndrome.)

But the results did not bear out the "efficacy" promised in his study's title. The vitamin-E-takers reported statistically significant improvements only in motor coordination and a few physical symptoms (bloating, breast tenderness, finger or ankle swelling, and weight gain).

Irritability, tension, depression, impaired social interactions, diminished mental ability, inefficiency, distorted eating habits, headaches, confusion, dizziness, and reduced sexual drive did not get significantly better.

Yet an earlier study by London found just the opposite: vitamin E improved all symptoms except bloating, breast tenderness, swelling, and weight gain.[3] Hmm.

London argues that you can't look only at improvements that met the scientific definition of "significant."

"If a symptom goes from |severe - where the woman wants to kill herself - to |mild' or |moderate,' that's clinically important," he says.

True, but if you don't reach statistical significance, it's more likely that the results were due to chance. Until someone does a larger study, the evidence on vitamin E remains in limbo.

Optivite: Disappointing ... and Dangerous? PMS was first described in the medical literature in 1931, but it wasn't until the early 1980s that most researchers began to explore its possible link with vitamins and minerals. One reason was Guy Abraham.

Abraham is the medical director of Optimox, Inc., which sells Optivite, a nutritional supplement for PMS sufferers. Optivite is a multi-vitamin-and-mineral that's especially rich in vitamin B-6, magnesium, zinc, and vitamin A.

Frankly, it made me suspicious to see a full-page ad for Optivite wedged between the articles on PMS in a 1987 issue of The Journal of Reproductive Medicine devoted to the subject. Still, Abraham's financial interest doesn't disqualify his theories.

In early, poorly designed studies, Abraham reported that Optivite offered dramatic relief for PMS. But there have been only three "double-blind" studies, in which neither the participants nor the researchers know who's getting a placebo and who's getting the vitamins. And one of those studies was flawed.[4] "Technically, I don't think it's a good study," admits Abraham.

He does stand behind a study he co-authored with Zaven Chakmajian, now in private practice in Dallas, and a new study by North Charles Hospital's Robert London, which hasn't been published yet.

But the women in Chakmajian's study weren't exactly cured. They weren't significantly less depressed, and breast tenderness or other signs of water retention didn't improve.[5] Anxiety did drop slightly-but-significantly (16 percent on average), and the participants' appetites and craving for sweets diminished by an impressive 31 percent. (At least that's what they said. The study didn't attempt to find out if they actually ate any less.)

But I'm not convinced that an increased appetite and a craving for sweets is such a problem. In one recent study, women ate about 200 to 300 extra calories - and a teaspoon or two more sugar - per day the week before menstruating.[6] So what? They returned to a lower calorie and sugar intake during the following weeks.

Burning for B-6. I might have been tempted to try Optivite, to see if it curbed my "anxiety" ... if it weren't for the hazards of vitamin B-6.

The six Optivites taken every day by Chakmajian's patients supplied a total of 300 mg of the vitamin. Women who have taken 500 mg or more of B-6 (often for PMS) for two months or longer have developed burning, shooting, or tingling pains or numbness in their hands and feet, clumsiness, or unstable gait - a condition known as sensory neuropathy.[7]

Fortunately, it goes away when the victims stop taking B-6. One report says that does as low as 50 mg can cause the disorder in sensitive people.[8]

"At doses less than 500 mg, neuropathy is not a problem," says Abraham, arguing that the report was not well-documented. But most B-6 experts are not that cavalier.

"I consider 300 mg to be in a gray area," says Robert Reynolds, of the U.S. Department of Agriculture. "We don't have sufficient data to say whether that dose can be take with complete confidence or complete panic."

Until someone gets sufficient data, 300 mg is too close to the danger dose for me. Especially when I'm not convinced that B-6 works.

Three earlier double-blind studies on vitamin B-6 alone (not Optivite) showed that it failed to alleviate the symptoms of PMS. Abraham says that's because the doses (50 to 200 mg) were too low.

In his own study, 500 mg relieved symptoms in 21 out of 25 patients.[9] But that study has been heavily criticized.

"Abraham didn't diagnose his patients properly," says David Rubinow, clinical director of the NIMH. Samuel Smith, of Sinai Hospital in Baltimore, agrees. "Forty percent of his patients didn't have PMS," he says. "They had symptoms during the [post-menstrual] phase."

Nevertheless, the NIMH hasn't given up on B-6. It's testing 200 mg a day on women with confirmed premenstrual syndrome (so far, none of the participants has had problems with that does). The results, says the NIMH's Peter Schmidt, "should be available in the next year or so."

Down the Primrose Path. Samuel Smith's solution, at least for PMS-sufferers who have breast tenderness or water retention, is now illegal.

The supplement - evening primrose oil - is 72 percent linoleic acid (the major component of safflower, corn, and soybean oil). Nine percent is gamma-linolenic acid, the so-called "active" ingredient.

The Food and Drug Administration recently won a lawsuit to prohibit the sale of evening primrose oil, on the grounds that the oil is not generally recognized as safe and is not approved for use as a food additive.

(I asked the FDA's John Thomas why this now-illegal supplement is still widely available in health food stores and through the mails. His answer: "The police can't catch everyone who goes through a red light.")

So far, only one well-designed study has tested evening primrose oil as a treatment for PMS.[10] The women taking the oil reported 11 percent less depression. Water retention, irritability, insomnia, and headaches did not improve.

Nevertheless, Smith recommends it for PMS patients who have breast tenderness, because of an earlier study on women who had breast pain (not necessarily from PMS), and because of his own "clinical experience." In other words, it works for his patients.

That's what worries me. When I asked Smith about vitamin E, he said, "Anecdotally, I can tell you it doesn't work with my patients."

That phrase sounded vaguely familiar. Ah yes. Vitamin-E-and-Optivite-researcher Robert London said the same thing about evening primrose oil.

Run It Off? You can't blame Jerilynn Prior for trying to test exercise's ability to prevent premenstrual symptoms. The researcher from the University of British Columbia got eight sedentary women to run an average of 32 miles per menstrual cycle. After three months, the women reported significantly less breast discomfort and "puffiness" than six women who did not participate.[11]

In a later study that lasted six months, eight other sedentary women who ran an average of 47 miles per cycle reported the same improvements, plus significantly less "personal stress" than six ordinarily active women who were not in training.[12]

But these studies were small, and weren't well-designed. What's more, Prior's - or anyone's - studies on exercise have an inherent problem: you can't give one group a placebo. If you're not exercising, you know it. So it's possible that the women who exercised felt better because they expected to.

Are Carbs the Cure? I was about to give up. So far, only a few studies had relieved any symptoms, and none of those had used women the National Institute of Mental Health would consider true PMS-sufferers.

Then I heard of a new study on carbohydrates by Judith Wurtman, of the Massachusetts Institute of Technology (MIT).[13]

Wurtman screened her participants with excruciating care. Each filled out questionnaires, recorded symptoms, sat through interviews with psychiatrists, tool personality and depression tests, and gave blood and urine samples. "We rejected more than 90 percent of the applicants because their PMS wasn't severe enough," she says.

The surviving 19 PMS-sufferers and nine non-sufferers ("controls") lived at an MIT research center to three to five days during the premenstrual and two days during the postmenstrual weeks of their monthly cycles. That way, Wurtman could monitor everything they ate.

"The women with severe PMS ate significantly more food, primarily carbohydrates - not just sweets, but rolls, pasta, and potato salad - but only when they were premenstrual," she reports. "The controls had no change in food intake."

But Wurtman didn't stop there. In a second phase of the study, she fed each woman a high-carbohydrate meal consisting of "a vary big, banal, bland bowl of corn flakes with low-protein, artificial milk."

One hour after the women with severe PMS consumed the cornflakes, they reported 43 percent less depression, 38 percent less confusion, 47 percent less fatigue, 42 percent less tension, and 69 percent less anger. "The effects were gigantic," says Wurtman. "The sort of thing you'd see with women on Valium."

The cornflakes had no effect on the controls' moods or on the PMS-sufferers' moods during their postmenstrual week.

Cornflakes, Not Snickers. But once again, it's possible that the women felt better because they expected to. To really test her theory, Wurtman would have to feed half the participants a high-carbohydrate meal and half a low-carbohydrate meal that looked and tasted identical.

Still, Wurtman's work pokes a hole in the popular advice to cut back on carbs. "The anecdotal reasoning went something like this," she explains. "Women who have PMS crave carbohydrates and throw knives at their husbands, so they shouldn't eat carbohydrates. But the advice has never been tested."

Instead of avoiding carbohydrates, she says, PMS-sufferers should eat more of them. "And they don't have to be Snickers," she adds. "Try pasta salad with vegetables, oatmeal with honey, sweet potatoes with marmalade, or breakfast cereals."

Back to the Drawing Board. I would be exaggerating if I said I can't wait to try out Wurtman's advice. (And I'm a bit skeptical, since I already eat lots of carbohydrates.)

Still, it's encouraging to think that Wurtman may be on to something, because no one else has found anything to lessen the symptoms of PMS.

Most of the PMS supplements on the market are either high-dose multi-vitamins and minerals or B-6 with a few other ingredients, such as herbs, a sprinkling of vitamins, or the amino acid DL-phenylalanine.

Interestingly, whenever I asked their manufacturers for evidence that the products work, I got the same answer: "We make no claims."

"PMS Formula" sure sounds like a claim to me.

Even prescription drugs have failed to alleviate PMS. "There are no pharmacological agents that have been consistently and convincingly superior to placebo except for those that cause cessation of ovarian function," says NIMH clinical director David Rubinow.

Those drugs (like Danocrine or Synarel) cause side effects that mimic menopause, including hot flashes, headache, decreased breast size, weight gain, vaginal atrophy, and bone loss.

That's what we have to look forward to when PMS ends? I'm depressed already.

[1] J. Reprod. Med. 33:340, 1988. [2] J. Reprod. Med. 32:400, 1987. [3] J. Am. Coll. Nutr. 2:115, 1983. [4] J. Reprod. Med. 32:435, 1987. [5] J. Appl. Nutr. 37:12, 1985. [6] Am. J. Clin Nutr. 49:252, 1989. [7] N. Eng. J. Med. 309:445, 1983. [8] Lancet i: 1168, 1985. [9] Infertil. 3:155, 1980. [10] J. Reprod. Med. 10:149, 1985. [11] Eur. J. Appl. Physiol. 55:349, 1986. [12] Fertil. Steril. 47:402, 1987. [13] Am. J. Obstet. Gynecol. 161:1228, 1989.