In the newest of the St. John’s wort studies in perimenopausal/menopausal women, a total of 100 Iranian women with an average age of 50 participated in a randomized, double-blind, placebo-controlled clinical trial comparing St. John’s wort with placebo in the treatment of hot flashes.[1] 50 women received 20 drops three times daily of St. John’s wort extract (Hypericin) that contained hypericin 0.2 mg/mL and 50 women received a placebo of distilled water. The study duration was two months. Clinical exams and interviews were performed at baseline, 4 weeks and 8 weeks. Treatment effectiveness was measured evaluating frequency, duration and severity of hot flashes as the main objective of the study.

In women taking St. John’s wort, the frequency began to decline during the 1^st and 2^nd months, but showed more improvement during the 2^nd month. There was no statistical change in hot flash frequency during the first month of placebo but did improve during the second month. Women who used St. John’s wort showed more improvement in hot flash frequency than placebo. The decline in duration of hot flashes was statistically significant at week 8 and the decline was much more evident in the St. John’s wort group. The severity of hot flashes was relieved in the St. John’s wort group during the 2 months of treatment and was more significant in the second month. Women in the placebo group did not show any significant decrease in severity of hot flashes during the 1^st month, but they did have some improvement during the 2^nd month, but not as great as those women in the St. John’s wort group.

Comments

St. John’s wort has emerged as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, and/or sleep problems either as an encapsulated standardized extract from 300 mg twice per day to three times per day, or a tincture/liquid extract ½ tsp 2-3 times per day, or in combination with other menopause therapies such as black cohosh, maca extract, kava or others.

Reference

[1] Abdali K, Khajehei M, Tabatabaee R. Effect of St. John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2): 326-331.

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.

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.

RESULTS: After 12 weeks of treatment, a non-significant difference in favor of the St. John’s wort group was observed in the daily hot flash frequency and the hot flash score. However, after those three months of treatment, women in the St. John’s wort group reported significantly better quality of life scores, and significantly fewer sleep problems compared to placebo.

Commentary: St. Johns wort research is expanding into the realm of use for perimenopause and menopause symptoms. Other recent studies have reported improvement in psychological, well-being and quality of life in symptomatic perimenopausal and menopausal women. In the current study, while not especially helpful for hot flashes, there was an improvement in quality of life scores and sleep problems. I commonly use St. Johns wort with black cohosh for women with hot flashes and mood issues during perimenopause and menopause. The research on each and even two studies using the combination of the two reveal that these two plants in combination are a premium option for perimenopausal and menopausal women with some of the most common of symptoms.

Reference

Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Mar-Apr;16(2):307-14

Patients were randomly assigned to drink one cup of Hibiscus or black tea two times per day for one month. Each infusion contained one tea sachet weighing 2 gm, placed in a tea pot with 240 ml boiling water and steeped for 20-30 minutes and then added one cube of sugar.

The average systolic blood pressure (SBP) in the hibiscus group decreased from 134.4 +/- 11.8 mm Hg at the start of the study to 112.7 +/- 5.7 mm Hg after 1 month. The average SBP changed from 118.6 +/-14.9 to 127.3 +/- 8.7 mm Hg in the black tea group during the same time period. There were no statistically significant effects on the mean diastolic blood pressure in either group.

Commentary:

It’s always gratifying to see a simple, safe, inexpensive herb studied for such a common problem. Hibiscus has been used historically for high blood pressure and contains several important ingredients including alkaloids, anthocyanins and quercetin. It is thought that the antioxidant and diuretic effects are the most important mechanisms.

References

Mozaffari-Khosravi H, Jalali-Khanabadi B, Afkhami-Ardekani M, et al. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Human Hypertension 2009;23:48-54.

This study was a single-blind controlled randomized clinical trial in women up to 20 weeks of pregnancy in Iran. 32 women received ginger and 35 received placebo. One ginger (250 mg) or placebo capsule four times per day was given over the course of four days. A four page questionnaire was used for each woman, one page per day for the four days. Women were also asked to record nausea intensity twice a day. At the end of four days, a researcher completed the questionnaire based on the woman’s responses.

Nausea intensity improved in 84% of those who used the ginger and in 56% of the women in the control group. The incidence of vomiting in the control group was 9% decreased and 50% decreased in the ginger group.

Commentary: At least four previous published studies have shown success in the use of ginger for nausea and vomiting of pregnancy. Doses of 1,000 mg – 1,500 mg per day have been used previously. The current study showed not only a positive effect, but women were satisfied with that effect and no complications were observed during the treatment period.

References

Ozgoli G, Goli M, Simbar M. Effects of ginger capsules on pregnancy, nausea and vomiting. J Alternative and Complementary Medicine 2009;15(3):243-246

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

St John’s wort was compared with a placebo in a double-blind, randomized clinical trial on symptoms and quality of life issues in perimenopausal women. Forty-seven 40 to 65 y.o. perimenopausal women who experienced three or more hot flashes per day were randomized to receive either 900 mg three times daily of a St. John’s wort extract or placebo for 3-months. Hot flash severity and frequency were evaluated and the Menopause-Specific Quality of Life questionnaire was used to evaluate menopause related quality of life.

After 12 weeks, only a small difference was seen favoring St. John’s wort in the frequency of hot flashes. A 30% improvement in 50% of the women was seen in the St. John’s wort group and only 23% in the placebo group. A significant reduction in sleep problems and depression was seen with St. John’s wort and the St. John’s wort group scored significantly better menopause related quality of life.

References

Al-Akoum M, Maunsell E, Verreault R, et al. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 2009; 16(2):307-314

Folic acid updates for pregnant women

It has been known for a considerable amount of time, that folic acid when given to women planning for pregnancy and during pregnancy, can lower the risk for neural tube defects. Based on the research up to that time, the US Preventive Services Task Force (USPSTF) first published their recommendations in 1996. This has recently been updated and the USPSTF has issued a new statement in May, 2009. Based on the observational evidence and randomized controlled trials published since 1996, the USPSTF found convincing evidence that supplements containing 0.4 to 0.8 mg of folic acid during the preconception period lowers the risk for neural tube defects.[i]

There now appears to be additional benefits for folic acid before conception and during pregnancy, possibly the prevention of cleft lip (BMJ 2007;334:464) and most recently, lowering the rates of severe congenital heart defects. In a Quebec study, investigators observed a drop in the prevalence of severe congenital heart defects after mandatory folic acid fortification of grains. The average prevalence of severe congenital heart defects at birth was 1.64 per 1000 births during the 9 years before the folic acid food fortification began and the rate fell by 6.2% yearly during the seven years studied, after the mandatory fortification.[ii]

Following the recommendation that all women of child bearing age should take a daily supplement containing 0.4 mg to 0.8 mg per day of folic acid is good, safe medicine and perhaps even more beneficial than previously thought.

References

[i] (Woffe T, Takacs-Witkop C, Miller T, Syed S. Folic acid supplementation for the prevention of neural tube defects: An update of the evidence for the U.S. Preventive Services Task Force. May 2009.150; (9): 632-639)

[ii] (Ionescu-Ittu R, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Time trend analysis in Quebec, Canada. BMJ 2009;338:b1673.)