Black Cohosh and St. John's Wort Combination for Menopausal Complaints

By Donald Brown, ND Founder and Director, Natural Product Research Consultants, Inc.; Advisory Board, American Botanical Council; President's Advisory Board, Bastyr University, Seattle; Advisor to the Office of Dietary Supplements at the National Institutes of Health. Dr. Brown is a consultant for Nature's Way, Inc.

Source: Uebelhack R, et al. Black cohosh and St. John's wort for climacteric complaints: A randomized trial. Obstet Gynecol 2006;107:247-255.

Abstract: In a double-blind, randomized, placebo-controlled trial, the efficacy of a combination of a standardized black cohosh extract and standardized St. John's wort extract was studied in women complaining of menopausal symptoms that included depression. Three hundred and one women (ages 45-60 years) experiencing climacteric complaints (menopausal symptoms) with a "pronounced psychological component" (i.e., depression) were entered in the trial. Inclusion criteria were: (1) climacteric complaints for at least three months; (2) complaints untreated for at least two months; (3) Menopause Rating Scale (MRS) score of 0.4 or more in at least three items; (4) Hamilton Depression Rating Scale (HAM-D) total score of 15-23 points; and (5) HAM-D item 1 score of ≥ 2 points.

Participants were randomized to receive either two tablets bid of a fixed combination of an isopropanolic extract of black cohosh (Cimicifuga racemosa; Remifemin®) and an ethanolic extract of St. John's wort (Hypericum perforatum; combination produced by Schaper and Brümmer GmbH & Co. KG, Salzgitter, Germany) for the first eight weeks followed by one tablet bid for weeks 8-16 or a matching placebo. Each tablet contained black cohosh extract standardized to 1 mg triterpene glycosides (corresponding on average to 3.75 mg native extract and 22.5-41.25 mg rootstock/rhizome) and St. John's wort extract standardized to 0.25 mg total hypericin (corresponding to 70 mg native extract and 245-350 mg of the herb).

The primary outcome measure was the change in the MRS from baseline to week 16. The MRS is a 10-item scale with each item being scored from 0 (no complaints) to 1 (severe complaints) in increments of 0.1. Symptoms rated include hot flashes, sleep disorders, joint and muscle symptoms, nervousness, disorders of sexuality, depressive moods, impaired memory, vaginal dryness, cardiac complaints, and urinary complaints. For this study, MRS items were grouped into four factors: hot flashes (items 1 and 3), atrophy (items 7-9), psyche (items 4-6), and soma (items 2 and 10). Secondary outcome measures included the HAM-D, the Clinical Global Impressions (CGI), and patient self-assessment. Patients were evaluated at baseline, week 8, and week 16.

A total of 294 women completed the 16-week study. Compared to baseline, the mean MRS total score was decreased in the treatment group by 34.8% at week 8 and 50% at week 16 compared to 21.7% and 19.6%, respectively, in the placebo group. The group difference between baseline and 16 weeks (mean group difference 0.141 ± 0.015; 95% confidence interval 0.112-0.171) as well as between baseline and week 8 was significant (P < 0.001). Superiority of treatment compared to placebo was noted for l0 items on the MRS, including hot flashes with a decrease of 53.4% at week 16 in the treatment group compared to 25.4% in the placebo group (P < 0.001). The HAM-D total score decreased by 41.8% (18.9 ± 2.2 to 11.0 ± 3.8 points) in the treatment group and 12.7% (18.9 ±2.1 to 16.5 ± 4.3) in the placebo group (P < 0.001). According to the CGI, treatment was judged to be "moderate" or "very good" for 78.8% of the treatment group compared to 14.9% for the placebo group (P < 0.001). There were no significant differences between groups in adverse events or in treatment tolerability.


Depression and anxiety are not uncommon symptoms in women during menopause. In fact, some drug research has focused on use of selective serotonin reuptake inhibitors (SSRIs) in low doses to treat hot flashes.1 The results to date have been poor. Although black cohosh extract has been shown in numerous studies to adequately address vasomotor symptoms, such as hot flashes, its effect on mild-to-moderate depression is not significant.2

Taking a page from traditional herbal medicine and combining two herbs with different mechanisms of action, this interesting clinical trial suggests that the combination of black cohosh and St. John's wort safely and effectively reduced menopausal symptoms such as hot flashes and depression. Practitioners should note the lower dose of St. John's wort used in this trial compared to those that have measured its efficacy alone for mild-to-moderate depression. It is interesting to note that a rather obscure 1999 clinical trial found that 900 mg/d of St. John's wort extract for 12 weeks effectively treated both vasomotor symptoms and depression in menopausal women.3 This trial used a dose of 900 mg/d and was not placebo-controlled. The combination product used in this trial is available commercially in Europe but not in the United States.

It should be noted that the daily dose of black cohosh and St. John's wort extracts was approximately 80 mg/d and 1,200 mg/d, respectively for the first eight weeks and 40 mg/d and 600 mg/d, respectively for the last eight weeks of the trial. Therefore, the dose of black cohosh for the first half of the trial was roughly double the dose used in more recent trials of black cohosh, and the dose of St. John's wort was 300 mg/d greater than the standard 900 mg/d used in most depression trials with the extract. The dose of black cohosh used in the second half of the trial is more in line with that used in more recent trials.

The results of this clinical trial suggest that the combination of black cohosh and St. John's wort may be useful in treating both vasomotor symptoms associated with menopause as well as depression. Future trials should focus on a more standardized dosage regimen and also include comparisons with black cohosh and St. John's wort alone. Current case reports in the literature and pharmacological studies suggest that St. John's wort should not be used concomitantly with cyclosporine, indinavir, irinotecan, digoxin, warfarin, theophylline, carbamazepine, phenprocoumon, and amitriptyline hydrochloride. It also should be used cautiously in women taking oral birth control pills. Due to risk of serotonin syndrome, it also is contraindicated in patients taking SSRIs.


1. Kockler DR, McCarthy MW. Antidepressants as a treatment for hot flashes in women. Am J Health Syst Pharm 2004;61:287-292.

2. Osmers R, et al. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 2005;105:1074-1083. Erratum in: Obstet Gynecol 2005;106:644.

3. Grube B, et al. St. John's wort extract: Efficacy for menopausal symptoms of psychological origin. Adv Ther 1999;16:177-186.