Premenstrual Syndrome, Part 1


Eighty percent of women experience premenstrual emotional or physical changes, whereas only about 20% to 40% of these women have difficulties as a result.

Eighty percent of women experience premenstrual emotional or physical changes, whereas only about 20% to 40% of these women have difficulties as a result. A much smaller number, about 2.5% to 5%,1 feel it has a significantly negative impact on their lives, to the point where work, relationships, and home life are jeopardized.

It is difficult to identify the cause in a condition that overlaps so broadly with normal physiology, affects so many, and has such a wide array of symptoms. Many theories have been explored and none found completely satisfying. Most likely, this is because it is such a complex interaction of factors both physiologic and social. While absolute levels of estrogen and progesterone are no different in premenstrual syndome (PMS) sufferers, we know that in women in whom both hormones are pharmaceutically blocked, PMS diminishes by 75%.2 It is likely that ovarian hormones affect the neurotransmitter, neuroendocrine, and circadian systems that influence mood and behavior differently in each woman. In this article, the author will discuss nutrition, exercise, and nutritional supplements and how they affect PMS. In part 2, the authors will discuss botanicals.

One of the theories that may prove to be the most accurate is that it is influenced by serotonin levels. Rapkin studied serotonin levels in women with PMS and those without and found that serotonin levels fell after ovulation in women with PMS.3 There is also evidence that estrogen levels affect the serotonin system. New therapies that have been successful include selective serotonin reuptake inhibitors (SSRIs), which further supports this approach. Numerous nutritional supplements can also increase serotonin levels. These include tryptophan and 5 hydroxytryptophan, S-adenosylmethionine (SAMe), magnesium, and B6. Only B6 has been studied for the treatment of PMS, which is discussed in the nutritional supplement section of this article. Acute tryptophan depletion was shown to correlate with PMS and aggravation of premenstrual symptoms.4

Excessive and incorrect prostaglandin (PG) synthesis has been implicated in the cause of PMS; a deficiency of prostaglandin E1 (PgE1) at the central nervous system has been proposed to be involved in PMS.5 There are many nutrients important for the synthesis of PgE1. These include magnesium, linoleic acid, vitamin B6, zinc, vitamin C, and vitamin B3. This theory is carried through as a basis for some of the nutritional therapies in the treatment of PMS.

Numerous natural alternative therapies are appropriate for the treatment of PMS including lifestyle changes, vitamin and mineral supplementation, herbal medicines, and natural hormones. Many of these have demonstrated their effectiveness in scientific studies; these are a mixture of controlled randomized clinical trials and uncontrolled. But at least an equal number have either shown no effect or an effect that was not statistically significant. Herein lies one of the curiosities of medicine, elegantly portrayed with PMS: Why do conventional scientific studies fail to demonstrate success with many of these natural therapies that women consistently rely on for their monthly successful treatments?

Perhaps the answer lies in the difficulty of determining what works for one person is different than what works for another. Double-blind, placebo-controlled, scientific studies attempt to find what works for as many people as possible, not what works best for an individual. The interaction between neurotransmitters, the body's steroids, circadian systems, mood, behavior, plus plants and nutrients from nature may remain scientifically elusive, but have often instinctually come upon safe and effective natural solutions. What follows is a guide to some of the natural approaches in the management and treatment of PMS that have been investigated.

Women who have PMS typically have dietary habits that are worse than the standard American diet. In a nutritional analysis published in 1983, Abraham reported that PMS patients consumed 62% more refined carbohydrates than women who did not have PMS, 275% more refined sugar, 79% more dairy products, 78% more sodium, 53% less iron, 77% less manganese, and 52% less zinc.6

As mentioned earlier, a deficiency of PgE1 may be a cause of PMS. The synthesis of PgE1 requires magnesium, linoleic acid, vitamin B6, zinc, vitamin C, and vitamin B3. Arachidonic acid is a precursor to PgE2, which has antagonistic effects with regard to PgE1. Vegetable oils are rich sources of linoleic acid and animal fats are the main dietary source of arachidonic acid. Patients with PMS would be wise to decrease their consumption of animal fats and increase their consumption of vegetable oils.

Many women with breast symptoms in the premenstrual phase benefit from avoiding caffeine. Even though scientific studies are conflicting on this subject, for many women, the practical results speak for themselves. Ernster conducted the first randomized study of a moderate number of women, in which for 4 months 158 women eliminated caffeine (coffee, tea, cola, chocolate) from their diets as well as caffeinated medications. She found a significant reduction in clinically palpable breast findings in the abstaining group compared with the control group, although the absolute change in the breast lumps was quite minor and considered to be of little clinical significance.7 Several other studies have been done with mixed reports, three showing no association between methylxanthines and benign breast disease and two showing positive correlations.

General regular physical exercise has been the subject of several controlled trials. In all of these, the results show that women who exercise regularly have less intense or fewer PMS symptoms. Aerobic training appears more effective at reducing PMS symptoms than strength training.8 Frequency of exercise seems more effective than intensity; gradual increase in running distances correlate directly with greater reductions in symptoms; and regular exercisers show improvement in all PMS parameters, eg, concentration, affect, pain, water retention, fear, guilt, and sadness.9

Multiple Vitamin/Minerals
It has been hypothesized that women with PMS are deficient in certain nutrients. Nutritional profiles, biochemical and hematological evaluations in eleven women have concluded that they did indeed have various nutritional deficiencies.10 Other biochemical investigations have found no evidence that premenstrual symptoms are caused by either absolute or relative nutritional deficiencies.11,12 Positive results seen in some studies with nutritional supplementation most likely represent a pharmacologic response to therapeutic doses of vitamins or minerals rather than reversing an underlying deficiency.

A multiple vitamin and mineral supplement may be helpful for women with PMS. A study was done in 1985 of a multiple called "Optivite." In a double-blind, placebo-controlled, crossover study, 16 of 23 subjects reported feeling better during the cycles in which they took the supplement, and seven reported feeling better during the placebo cycles.13 When selecting a multiple vitamin and mineral supplement, formulations made especially for women take into account some of the special nutritional needs of women.

A second study on the same product was done in 199114 to assess the effectiveness of a vitamin/mineral supplement in controlling symptoms of premenstrual syndrome. This double-blind randomized study of 44 women divided women with PMS into four subgroups depending on their symptoms. Subjects were randomly assigned to receive either placebo or 6 or 12 tablets of the supplement a day for three menstrual cycles. All subjects had significant differences in severity of symptoms between the follicular and luteal phase of the control cycle. Comparing pretreatment versus posttreatment luteal phase scores, significant placebo effects were noted for two PMS subgroups: PMS-A (nervous tension, mood swings, irritability, anxiety) and PMS-C (headaches, craving for sweets, increased appetite, heart pounding, fatigue). Six daily tablets of Optivite was associated with significant reduction in all symptom categories: PMS-A, PMS-C, PMS-D (depression, insomnia, forgetfulness, crying, confusion), except PMS-H (weight gain, breast tenderness, swelling of extremities, abdominal bloating). Twelve tablets of Optivite was associated with significant reductions in all PMS subgroups.

Vitamin B6
As noted earlier, declining levels of serotonin, and also of dopamine, have been implicated in the etiology of PMS. Vitamin B6 (pyridoxine) is thought to be unique in its ability to increase the cerebral synthesis of several neurotransmitters, including serotonin and dopamine, and more than a dozen studies have been done of vitamin B6 and PMS. These studies used vitamin B6 at a dose of 50 to 500 mg per day. Some of them found no effect, but others reported a substantial and broad effect. Abraham and Hargrove, Barr and Hallman reported positive effects, although the symptoms did not completely disappear.15-17 Five studies demonstrated some benefits but did have some ambiguous effects.18-22 An overview of these studies has been published in the British Journal of Obstetrics and Gynaecology.23

Essential Fatty Acids
The main strategy of supplementing with essential fatty acids is an attempt to raise the body's own formation of PgE1. The most popular method of doing so has been to supplement with evening primrose oil (EPO) to supply increased levels of gamma linolenic acid. Several studies show positive results, but some of the studies did not include a placebo group, and three studies failed to show a statistically significant difference between the treatment group and the placebo group.24-26 Four double-blind, crossover, controlled trials of EPO have demonstrated a significant effect over the placebo group.27-30 One of these studies used 3 g of EPO per day; the others used 4 g per day. Other sources of oils that contain gamma linolenic acid and raise PgE1 levels include borage oil, black currant oil, and rapeseed oil.

Magnesium has shown some beneficial effect in the treatment of PMS. The mechanism of magnesium and its possible role in PMS are not well understood, but we do know that magnesium is involved in essential fatty acid metabolism and pyridoxine (vitamin B6) activity. Three small randomized clinical trials have investigated supplementation with magnesium. Two reported significant effects compared with placebo, but the symptoms were different. In the first, the positive results were for overall scores and negative affect.31 The second found a significant effect but only for symptoms of fluid retention.32 The same authors of this study conducted another study and reported no significant effects of magnesium when used alone but there were improvements in anxiety symptoms when magnesium was combined with vitamin B6.33

Calcium Carbonate
A recent randomized, double-blind placebo-controlled, multicenter clinical trial was conducted to test the hypothesis that problems in calcium regulation may underlie some of the symptoms of PMS. Four hundred ninety-seven women were enrolled and given either 1,200 mg of calcium carbonate or placebo for three menstrual cycles.34 During the luteal phase of the treatment cycle, a significantly lower symptom complex score was observed in the calcium group for both the second and third months. By the third month, calcium effectively resulted in a 48% reduction in total symptom scores from baseline compared with a 30% reduction in the placebo group. All four symptom factors (ie, negative mood affect, water retention, food cravings, and pain) were significantly reduced by the third treatment cycle. Earlier calcium studies in women with PMS have found that calcium supplementation effectively alleviates the majority of premenstrual mood disorders.35,36

Vitamin E
Vitamin E is probably not a big player in PMS relief, although studies have demonstrated a reduction in premenstrual nervous tension, headache, fatigue, depression, insomnia, and breast tenderness.37 Three studies have demonstrated that vitamin E is clinically useful in relieving pain and tenderness of the breasts, whether cyclical (premenstrual) or noncyclical.38-40 The studies have been done with varying dosages: 150 international units (IU), 300 IU, and 600 IU per day.

Part 2, Botanical and Natural Treatments


Tori Hudson, ND, is a professor, National College of Naturopathic Medicine, and director, A Woman's Time, PC, Portland, Ore.


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4. Menkes D, Coates D, Fawcett P. Acute tryptophan depletion aggravates premenstrual syndrome. J Affective Disord. 1994;32:37-44.

5. Jakubowica D. The significance of prostaglandins in the premenstrual syndrome. In: Taylor R, ed. Premenstrual Syndrome. London, England: Medical New-Tribune; 1983:16.

6. Abraham G. Nutritional factors in the eitiology of the premenstrual tension syndromes. J Reprod Med. 1983; 28:446-464.

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9. Aganoff J, Boyle G. Aerobic exercise, mood states and menstrual cycle symptoms. J Psychosom Res. 1994;38:183.

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11. Mira M, Stewart P, Abraham S. Vitamin and trace element status in premenstrual syndrome. Am J Clin Nutr. 1988;47:636-641.

12. Chuong C, Dawson E, Smith E. Vitamin E levels in premenstrual syndrome. Am J Obstet Gynecol. 1990;163:1591-1595.

13. Chakmakjian Z, Higgins C, Abraham G. The effect of a nutritional supplement, Optivite for women, on premenstrual tension syndrome: effect of symptomatology, using a double blind crossover design. J Appl Nutr. 1985;37:12.

14. London R, Bradley L, Chiamori N. Effect of a nutritional supplement on premenstrual symptomatology in women with premenstrual syndrome: a double-blind longitudinal study. J Am Coll Nutr. 1991;10(5):494-499.

15. Abraham G, Hargrove J. Effect of vitamin B6 on premenstrual tension syndromes: a double blind crossover study. Infertility. 1980;3:155-165.

16. Barr W. Pyridoxine supplements in the premenstrual syndrome. Practitioner. 1984;228:425-427.

17. Hallman J, Oreland L. Therapeutic effect of vitamin B6 in the treatment of premenstrual syndrome. A double-blind cross-over study. Comprehensive summaries of Upsala Dissertations from the Faculty of Medicine. 1987;88:1-15.

18. Smallwood J, Ah-Key D, Taylor I. Vitamin B6 in the treatment of premenstrual mastalgia. Br J Clin Pract. 1986;40:532-533.

19. Stokes J, Mendels J. Pyridoxine and premenstrual tension. Lancet. 1972;1:1177-1178.

20. Williams M, Harris R, Dean B. Controlled trial of pyridoxine in the premenstrual syndrome. J Int Med Res. 1985;13: 174-179.

21. Kendall K, Schnurr P. The effects of vitamin B6 supplementation on premenstrual symptoms. Obstet Gynecol. 1987;70: 145-149.

22. Doll H, Brown S, Thurston A, Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract. 1989;39:364-368.

23. Kleijnen J,ter Jtiet G, Knipschild P. Vitamin B6 in the treatment of the premenstrual syndrome - review. Br J Obstet Gynaecol. 1990;97:847-852.

24. Callender K, McGregor M, Kirk P, Thomas C. A double-blind trial of evening primrose oil in the premenstrual syndrome: nervous symptom subgroup. Hum Psychopharmacol. 1988;3:57-61.

25. Khoo S, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust. 1990; 153:189-192.

26. Collins A, Cerin A, Coleman G, Landgren B. Essential fatty acids in the treatment of premenstrual syndrome. Obstet Gynecol. 1993;81:93-98.

27. Puolakka J, Makarainen L, Viinikka L, Ylikorkala O. Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors. J Rep Med. 1985;30(3):149-153.

28. Ockerman P, et al. Evening primrose oil as a treatment of the premenstrual syndrome. Rec Adv Clin Nutr. 1986;2: 404-405.

29. Massil H, et al. A double-blind trial of Efamol evening primrose oil in premenstrual syndrome. 2nd Internat Symp on PMS, Kiawah Island, Hawaii. September 1987.

30. Casper R. A double blind trial of evening primrose oil in premenstrual syndrome. 2nd Internat Symp on PMS. Kiawah Island, Hawaii. September 1987.

31. Facchinetti F, Borella P, Sances G, et al. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991;78:177-181.

32. Walker A, De Souza M, Vickers M, et al. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Women's Health. 1998;7:1157-1165.

33. De Souza M, Walker A, Robinson P, Bolland K. A syndergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, cross-over study. J Women's Health Gender-Based Med. 2000;9:131-139.

34. Thys-Jacobs, et al. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Am J Obstet Gynecol. 1998; Aug: 444-452.

35. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium Supplementation in Premenstrual Syndrome. J Gen Intern Med. 1989;4(May/June):183-189.

36. Penland J, Johnson P. Dietary calcium and manganese effects on menstrual cycle symptoms. Am J Obstet Gynecol. 1993;168(5):1417-1423.

37. Abraham G. Nutritional factors in the etiology of the premenstrual tension syndromes. J Reprod Med. 1983;28:446-464

38. London R, Sundaram G, Manimekalai S, et al. Mammary dysplasia: Endocrine parameters and tocopherol therapy. Nutr Res. 1982;7:243.

39. London R, Sundaram G, Schultz M, et al. Endocrine parameters and alpha-tocopherol therapy of patients with mammary dysplasia. Cancer Res. 1981;41:3811-3813.

40. London R, Sundaram G, Murphy L, Goldstein P. Evaluation and treatment of breast symptoms in patients with the premenstrual syndrome. J Reprod Med. 1983;28(8):503-508.

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