Women who had the highest intake of thiamine were 25% less likely to develop PMS than those with the lowest intake. Women with the highest intake of riboflavin were 35% less likely to develop PMS. The intake of all B vitamins together in a B-complex supplement did not appear to lower the risk for PMS.

Comments: Vitamin B6 (pyridoxine) has shown benefits in treating PMS in most, but not all studies, and has shown a substantial and broad effect on the whole range of PMS symptoms in the positive studies. Doses have ranged from 50 gm to 500 mg per day. Given this body of research and information spanning since 1973, I’m not sure what compelled the investigators in this current study to track vitamins B1 and B2, rather than vitamin B6.

Reference: Chocano-Bedoya P, et al. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr 2011 May; 93:1080

The evidence for the use of chaste tree berry in the treatment of mastalgia has been reported in both randomized and non-randomized studies. A large open study without a control group of 1634 women with cyclic mastalgia as part of their premenstrual syndrome demonstrated that after 3 months of treatment, 80% of patients rated their response as a good and 81% rates it as a very good treatment for their mastalgia. [1] In a prospective, multi-center trial using chaste tree in 50 patients with premenstrual cyclic mastalgia, 43 women were treated daily with chaste tree for three consecutive menstrual cycles.[2] By the end of the study period, cyclical mastalgia decreased significantly along with a smaller degree of improvement even 3 months after stopping the plant. Thirty-eight women rated the effectiveness as moderate to excellent, with 5 reporting no effect. In a randomized controlled trial, 97 women with cyclical mastalgia had twice the decrease in intensity of pain after one or two treatment cycles as compared to placebo.[3] The duration of pain also improved in the chaste tree group. In the chaste tree group, half the women did not have severe pain at all during any time of the menstrual cycle and only 25% had severe pain for 4% of the days compared with severe mastalgia one fifth of the time before their use of chaste tree began. In a randomized trial of premenstrual dysphoric disorder, comparing chaste tree with an SSRI, 58% of patients being treated with chaste tree had an improvement in their cyclical mastalgia and 68% of patients had improvements in their psychological symptoms.[4] In a randomized controlled placebo controlled trial, 170 women were given chaste tree or placebo for three consecutive cycles. The improvement in breast pain was greater in the chaste tree group (52%) compared with the placebo group (24%). [5]

Consider a standardized extract of chaste tree berry—usually one capsule per day all month long for a minimum of two but preferably three consecutive months.

References

[1] Loch E, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med 2000;9:315-320.)

[2] (Berger D, Schaffner W, Schrader E, Meier B, Brattstrom A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome. Arch Gynecol Obstet 2000;264:150-153.)

[3] ( Halaska M, Beles P, Gorkow C, Sieder C. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study. Breast 1000; 8:175-181. )

[4] (Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol 2003;18:191-195.)

[5] (Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. Br Med J 2001;322:134-137.)

Symptoms were rated using the Daily Symptom Report, The State Anxiety Inventory, the Beck Depression Inventory and the Aggression Questionnaire and Barratt Impulsiveness Scale. Numerous hormones and physiological markers were also measured in the follicular and luteal phases: follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, prolactin, testosterone, cytokine interleukins= IL-1B, IL-6, IL-8, interferon and tumor necrosis factor alpha.

St. John’s wort was statistically more beneficial than placebo in food cravings, swelling, poor coordination, insomnia, confusion, headaches, crying and fatigue. There were no significant effects of St. John’s wort compared with placebo in any of the biochemical blood measurements. St. John’s wort was not statistically more beneficial in anxiety, irritability, depression, nervous tension, mood swings, feeling out of control and pain-related symptoms during two cycles of treatment. However, these pain-related symptoms appeared to improve more than placebo towards the end of each treatment period

Commentary: The results of this PMS study demonstrate once again, the benefit of St. John’s Wort for the treatment of PMS. In this study, it was determined their PMS was mild. The benefit received by women taking St. John’s Wort was achieved during the first menstrual cycle in which it was taken. While St. John’s Wort did not prove to be statistically better than placebo for mood and pain-related PMS symptoms, the pain symptoms did appear to improve more than placebo towards the end of each treatment period, implying that there may be more pain benefits with St. John’s wort after a longer duration of treatment. Several other studies have shown benefit with St. John’s wort.

Reference: Canning S, Waterman M, Orsi N, et al. The efficacy of Hypericum perforatum (ST John’s Wort) for the treatment of premenstrual syndrome. CNS Drugs 2010; 24(3):207-225.

This study was a double blind clinical trial in 150 women in Iran. Two groups of 75 women each were evaluated for severity and duration of breast pain which was measured according to a breast pain chart and something called a Visual Analog Scale.

Chewable tablets of either vitamin E 200 mg tablets or a placebo were given twice a day for 4 months, and again, the severity and duration of breast pain was evaluated at the end of the second and fourth month. The results at two months for vitamin E were dramatically better than placebo in severity and duration, and appear to be achievable in about 70% of the women. The improvement was seen as soon as two months, and no continued improvement after 4 months.

Commentary: Other studies have been conducted in vitamin E and breast pain. In 1997, Khanna et al compared vitamin E with a drug called Danazol. Vitamin E reduced pain in 41% of the women in the studies and Danazol had similar pain reduction in 72% of the women. Clearly the drug helped more women, but the side effects of that drug are significant and one third of the women developed other side effects. Meyer et al did a study in 1990 but did not show any benefit from Vitamin E. Ernester in 1985 studied 201 women with mastalgia as it relates to fibrocystic breast disease. He concluded that vitamin E was not effective, but he was not evaluating breast pain as a distinct issue. In 2004, Bespalov et al studied 66 women with a combination of beta-carotene, vitamin E, vitamin C and garlic powder. There was a reduction in the severity of mastalgia, premenstrual syndrome, infrequent menses and menstrual cramping as well as a reduction in symptoms of fibromatosis in 75% of the women compared with 45% of women on placebo.

If vitamin E alone is not sufficiently helpful in reducing mastalgia, evening primrose or borage oil should be considered, as well as carotenoids, iodine, eliminating caffeine, lowering saturated fats in the diet and increasing fiber.

References

Parsay S, Olfati F, Nahidi S. Therapeutic effects of vitamin E on cyclic mastalgia. The Breast Journal 2009;15(5):510-514.

The daily dose of herbal products given were 3 tablets containing 5400 mg of St. John’s wort standardized to contain 990 mcg hypericin, 9 mg hyperforin and 18 mg flavonoid glycosides. The daily dose of chaste tree berry was one tablet of an extract equivalent to 1000 mg of dry fruit. This was not a standardized extract. There was a matching placebo group. Participants recorded the severity of their PMS symptoms using the Abraham’s Menstrual Symptom Questionnaire.

The active treatment group was statistically superior to placebo for total PMS-like symptoms as well as subgroups of PMS depression and PMS food cravings.

Commentary: Based on previous research in PMS and chaste tree berry and PMS and St. John’s wort, as well as my clinical experience, it is not surprising that a combination of the two plants would be effective. PMS symptoms are common in regularly menstruating women, and it is also a common phenomenon in peri-menopausal women whose cycle and hormonal regularity is beginning to change. While this study evaluated a small group of women, it does address a significant population of women— those who are peri-menopausal and newly or still, experiencing PMS symptoms.

Reference:

Van Die M, Bone K, Burger H, et al. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: Findings from a subpopulation analysis. J Alternative and Complementary Medicine 2009;15(9):1045-1048.

Peer-reviewed research studies were located in various data-bases searching for studies investigating vitamin D and depression, seasonal affective disorder, PMS, postpartum depression, perinatal depression, depressive disorder or mood disorder in women. Eleven studies were initially identified, but five were eliminated because they did not meet the inclusion criteria. Of these six studies, four reported significant results showing an association between low serum 25 (OH) D levels and symptoms of a mood disorder, SAD, major depressive disorder, or PMS. One study of major depression and one on SAD did not report an association. Only one of the four positive studies was a randomized controlled trial.

Vitamin D receptors are involved in the regulation of glucocorticoid signaling and dysfunctional glucocorticoid signaling and increased glucocorticoids have been implicated in major depressive disorder. Other biochemical mechanisms may also exist, associating vitamin D with mood disorders.

I look forward to more research on specific mood disorders in women and vitamin D levels.

References:

Murphy P, Wagner C. Vitamin D and mood disorders among women: an integrative review. J Midwifery Women’s Health 2008;53:440-446.

After the treatment period, there was a significant decrease in the overall severity of symptoms and physical and psychological symptoms in both the Ginkgo group (23.68%) and the placebo group (8.74%). The average decrease in the severity of symptoms was significantly more in the Ginkgo group compared to the placebo group.

Comments: The results of this study demonstrated that ginkgo was more effective than placebo in reducing the severity of symptoms and the severity of physical and psychological symptoms in young women in Iran, with PMS. A previous study also found benefits with ginkgo and PMS, especially with breast tenderness and fluid retention. They also saw significant improvements in irritability and aggression, compared with placebo. The current study confirms the benefits of a standardized extract of ginkgo for the treatment of PMS. Based on the published -research to date, standardized extracts of – Vitex agnus castus (chaste tree berry), Hypericum perforatum (St. Johns wort) and Ginkgo biloba (ginkgo), appear to be the most effective botanical treatments for PMS. I would encourage women and their practitioners to seek PMS formulas that have at minimum, these three botanicals in the formulation.

References

Ozgoli G, Selselei E, Mojab F, Majd H. A randomized, placebo-controlled trial of ginkgo biloba in the treatment of premenstrual syndrome.

The mean total Premenstrual Syndrome Diary (PMSD) score decreased from 29.23 at baseline to 6.41 at the end of the third cycle for the Vitex group and from 28.14 at baseline to 12.64 at the end of the third cycle for the placebo group. The difference in the PMSD score from baseline to the third cycle was significantly lower in the treatment group than in the placebo group. The Premenstrual Tension Syndrome Self-Rating Scale (PMTS) decreased from 26.17 at baseline to 9.92 for the treatment group and from 27.10 to 14.59 for the placebo group; similar positive results to the PMSD scores.

Comments: I’ve long used Vitex for the treatment of PMS and in my opinion, it is the single most important plant for the treatment of PMS. The effect of Vitex is on the hypothalamus-hypophysis axis and results in an increased secretion of luteinizing hormone which then favors a progesterone effect. Several other placebo controlled studies have found that Vitex reduced a variety of PMS symptoms. The current study adds to the clinical relevance of this plant in the treatment of moderate to severe symptoms of PMS.

References

He Z, Chen R, Zhou Y, et al. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas 2009; 63:99-103

At the end of treatment, the severity of dysmenorrhea decreased in all groups and no differences were found between the groups in pain severity, pain relief or satisfaction. More women in the ginger group became completely pain free, vs. the mefenamic acid and ibuprofen groups. The rate of satisfaction from the treatments was 20/50 women in the mefenamic acid group, 22/50 women in the ibuprofen group and 21/50 women in the ginger group.

The cause of menstrual cramps is thought to be due to an increased production of prostaglandins in the endometrium (lining of the uterus). Menstrual blood of women with primary dysmenorrhea has greater amounts of the prospasmodic and proinflammatory prostaglandins, PGE2 and PGF2 alpha. Both mefenamic acid and ibuprofen act as inhibitors of the synthesis of these prostaglandins. It is thought that the anti-inflammatory properties of ginger are due to the gingerols, also leading to and prostaglandin reduction as well as some inflammatory substances. Consider using ginger root either alone, or in combination with other important natural ingredients in the relief of menstrual cramps such as cramp bark, niacin, vitamin B6, valerian, wild yam and more.

References

Ozgoli G, Goli M, Moattar F.  Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea.  J Alternative and Complementary Med 2009; 15(2):129-132.

According the Hamilton Depression Rating Scale, 15 of 25 women in the saffron group responded to treatment vs only 1 of 25 in the placebo group. (P< 0.0001). Again, a significant difference was seen between cycles 3 and 4 with a statistically significant difference by the study end (P< 0.0001).

Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Agha-Hosseini M, Kashani L, Aleyaseen A, et al. BJOG 2008;115:515-519.

Commentary: Improvements in the Total Premenstrual Daily Symptoms and the Hamilton Depression Rating Scale with saffron should give us definite motivation to try this simple treatment. Saffron has been previously shown to have an antidepressant effect in women with mild to moderate depression, through a serotonergic mechanism, so it’s not surprising that it would work in PMS. Research on PMS in the last several years has pointed strongly to the etiology being the dysregulation of the serotonergic system. This is why we have seen conventional medical practitioners focus on the use of SSRIs in treatment.

This is the first clinical trial I’ve seen in the use of saffron for the treatment of PMS. While only a small study and short follow-up, the positive results warrant further study, and in the meantime, accumulating some clinical experience.