A study of St John’s wort liquid extract showed a statistically decline in hot flashes severity, duration and frequency in the SJW group compared to placebo at week 8.[1]

Another double blind randomized clinical trial demonstrated that after 3 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. [2]

About ten years ago, a non placebo controlled, drug monitoring study was conducted in women with menopause symptoms using 900 mg of St. Johns wort for 12 weeks. About three quarters of the women experienced improvement in both the self-rating scale and the physician rating, and significantly improved in psychological and psychosomatic symptoms as well as a feeling of sexual well-being.[3]

The first of three studies using St. John’s wort and black cohosh was published in 1999. This double-blind, randomized, placebo-controlled trial used St. John’s wort and black cohosh made by the makers of Remifemin.[4] The Kupperman index for the combination product decreased from 31.4 to 18.7 compared with a decrease in the placebo group from 30.3 to 22.3. Psychological symptoms also improved significantly in the black cohosh/St. John’s wort combination group.

A double-blind randomized placebo-controlled study was done using a combination trial of black cohosh and St. John’s wort. The mean Menopause Rating Scale score decreased 50% in the treatment group and 19.6% in the placebo group.[5] The Hamilton Depression Rating Scale score decreased 41.8% in the treatment group and 12.7% in the placebo group. In both testing measures the St. John’s wort + black cohosh group was significantly superior to the placebo group.

Another black cohosh/St. John’s wort trial was carried out in peri or postmenopausal Korean women, and was published in 2007.[6] Mean Kupperman index scores at 4 and 12 weeks were significantly lower in the treatment group (P < 0.002). At the end of the study, the average decrease in the Kupperman Index was 20 points in the treatment group and only 8.2 points in the placebo group (P < 0.001). Vaginal dryness and low libido were two symptoms that did not improve, but the average hot flash scores were significantly lower in the black cohosh/St. Johns wort group.

Finally, a study was done in which a combination of black cohosh with or without St. John’s wort was used in 6141 women at 1287 outpatient gynecologists in Germany in a prospective, controlled open-label observational study.[7] The greatest changes occurred with the combination therapy for nervousness/irritability and mood swings, but in the area of depression, there was a reduction in both treatment groups.

St. John’s wort is emerging as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, as a single agent, or in combination with other therapies.

References

[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.

[2] 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.

[3] Grube B, Walper A, Whatley D. St. John’s wort extract: Efficacy for menopasual symptoms of psychological origin. Adv Ther 1999;16:177.

[4] Boblitz N, Schrader E, Henneicke-Von Zepelin H, et al. Benefit of a fixed drug combination containing St. John’s wort and black cohosh for climacteric patients-results of a randomised clinical trial )poster presentation from 6^th Annual Symposium on Complementary Health Care, Exeter, England, December 2-4 1999). Focus Alt Comp Ther 2000;5(1):85-86.

[5] Uebelhack R, Jens-Uwe Blohmer, et al. Black cohosh and St. john’s wort for climacteric complaints. Obstet Gynecol 2006;107:247-255.

[6] Chung D, Kim H, Park K, et al. Black cohosh and St. John’s wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007;48(2):289-294.

[7] Briese V, Stammwitz U, Friede M, et al. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment- Results of a large-scale, controlled, observational study. Maturitas 2007;57:405-414.

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.

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

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.)

The pharmacokinetics of the desogestrol was also not affected by co-administration of the St. John’s wort extract. There was a small decrease in ethinylestradiol and 3- ketodesogestrel but it was not considered significant. In addition, there was no break through bleeding induced by the addition of the St. John’s wort extract.[1]

Comments

The results of this study are in contrast to other previous reports and studies. Two reports have shown break-through bleeding and spotting with co-administration of St. John’s wort and OCs.[2],[3]

Three studies indicate an alteration of the pharmacokinetics of the OC with co-administration of St. John’s wort. [4], [5], [6] These studies used a different St. John’s wort preparation (80% methanolic extract) and at a much higher dose (900 mg) containing a much higher amount of hyperforin (20-35 mg) than the current study.

The lower daily total dose and hyperforin intake would appear to be the likely reason for the lack of interaction of the St. John’s wort extract with the OC pharmacokinetics in this current study. Accordingly, using a lower dose St. John’s wort extract with reduced hyperforin content does not appear to interact with OC nor cause breakthrough bleeding (an indication of possible ovulation).

References

[2] Ernst E. Second thoughts about safety of St. John’s wort. Lancet 1999;354:2014-2016.

[3] Raetz A, vonMoos M, Drewe J. Johanniskraut: ein Phytopharmakon mit potentiell gefahrlichen Interaktionen. Praxis 2001;90:843-849.

[4] Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St. John’s wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003;56:683-690

[5] Hall S, Wang Z, Huang S, Hamman M, et al. The interaction between St. John’s wort and an oral contraceptive. Clin Pharmacol Ther 2003; 74:525-535.

[6] Murphy P, Kern S, Stanczyk F, Westhoff C. Interaction of St. John’s wort with oral contraceptives: effects on the pharmacokinetics of norehindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005;71:402-408

6141 women at 1287 outpatient gynecology offices were treated with recommended doses of black cohosh isopropanol extract,Remefemin (1 cap bid) or Remifemin plus combination with St. Johns wort (1 or 2 tablets bid) at the discretion of the clinician.

Treatment responses were assessed on the menopause rating scale (MRS), an established standard for evaluating menopause symptoms. The primary effectiveness variable was the change in the MRS subscore PSYCHE (including depressive mood, nervousness, irritability, impaired performance and memory) from baseline to month three.

Of the enrolled women, 3027 received the black cohosh only and 3114 received the black cohosh/St. Johns wort combination. During the study, 244 women changed treatment from monotherapy to the combination product and 87 women changes from the combination product to monotherapy.

Women receiving combination therapy had significantly higher PSYCHE scores, i.e. worse symptoms than those in the black cohosh group. More women in the combination group had clightly more concomitant diseases.

The symptom scores improved in both groups. The changes in the PSYCHE symptoms were greater in the combination therapy group than in the black cohosh only group at month 3 and 6. The greatest effects, with both treatments, were seen with hot flushes and night sweats and these were similar. Results were evident at month 3, and even more so, at month 6.

Both treatments were very well tolerated. The rate of adverse events related to the treatments was very small, at 0.16% or 10 cases. Seven cases were in the black cohosh only group and three in the combination group.

Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin H. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment – Results of a large-scale, controlled, observational study. Maturitas 2007; 57(4): 405-414.

Commentary: The results from the large study supports the effectiveness of black cohosh preparations alone or in combination with St. Johns wort for relief common menopausal symptoms such as hot flushes/nightsweats and psychological symptoms. The combination of the two herbs, appears to be the best approach for symptoms that include depressive moods, nervousness, irritability, and impaired memory.