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: Osmers R, et al. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 2005;105: 1074-1083.
Abstract: In a randomized, multicenter, double-blind, placebo-controlled clinical trial, the efficacy of a standardized black cohosh preparation was studied in 304 postmenopausal women. Subjects were at least 45 years of age and were selected from 24 gynecological practices in Germany. Women entered in the trial were required to have an interval of at least 12 months since their last regular menstruation or an interval of at least six months since their last regular menstruation plus follicle-stimulating hormone (FSH) of > 50 U/L. Additionally, climacteric complaints as defined by the Menopause Rating Scale I (MRS) of > 0.4 in at least three items. Participants were randomized to receive either 20 mg of black cohosh (Cimicifuga racemosa) extract (Remifemin®, Schaper & Brummer GmbH & Co. KG, Salzgitter, Germany) or placebo bid for 12 weeks.
Clinical examinations were performed pretreatment and at weeks 4 and 12. The primary outcome measure was the intensity of climacteric symptoms as defined by the MRS, 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. The primary endpoint was defined as change from baseline in the MRS mean score, analyzed in a linear regression model considering the following cofactors and covariates: age at study onset, MRS at baseline, FSH at baseline, and others that are beyond the scope of this review. Secondary measures included changes in MRS subscores (hot flashes [includes hot flashes, sweating, sleep disorders], psyche [includes depressive moods, nervousness, nervous irritability, impaired memory and performance], soma [includes cardiac complaints, joint and muscle symptoms], atrophy [includes disorders of sexuality, urinary complaints, vaginal dryness], and safety variables).
A total of 268 women successfully completed the trial. At the end of 12 weeks, the difference in the decrease in MRS score was significantly greater in the black cohosh group compared to placebo (P = 0.027). When confounders and covariates were considered, this difference became more significant. Notable is the fact that when considering women in the early stages of menopause and lower baseline FSH (FSH = 20 U/L and one year duration of climacteric complaints) compared to women in later stages of menopause (FSH = 40 U/L and three years duration of symptoms), the differences in MRS scores became even greater (P < 0.001). The MRS subscore for hot flashes changed most significantly in the black cohosh group compared to placebo (P = 0.007), although significant, but smaller differences were noted for the atrophy (P = 0.012) and psyche (P = 0.019) subscores. The difference on the soma subscore did not reach significance. These differences again were greater among women in early menopause compared to those in later stages.
All 304 women originally enrolled in the trial were included in the safety analysis. In the black cohosh group, 50 (32.7%) women reported 71 adverse events compared to 47 (31.1%) in the placebo group. A causal relationship to the study medication was judged to be at least possible in six events (3.9%) reported in the black cohosh group compared to 7 (4.6%) in the placebo group. Most of the adverse events were mild in nature with gastrointestinal complaints being distributed equally between both groups. There were no notable increases in liver enzymes in either group during the 12 weeks of the trial.
Comments
This large randomized trial supports the use of black cohosh extract to treat menopausal symptoms, most notably hot flashes. However, it is the first successful trial to demonstrate that the duration of menopause symptoms and baseline FSH levels may be a predictor of how effectively it works. Namely, women with symptoms lasting one year or less and with lower baseline FSH levels are more likely to have a reduction of symptoms than women with a longer duration of symptoms and higher baseline FSH. The effect size for the black cohosh group was -0.03 to -0.05 MRS units, similar to the -0.036 MRS units noted for recent studies using conjugated estrogens.1
Notable as well is the finding that black cohosh did not appear to have any hepatotoxic effects according to serum enzyme measures. Issues regarding the potential hepatotoxicity of black cohosh have arisen over the past couple of years, including isolated case reports.2 The authors do report that a longer safety trial is currently underway.
The publication of this trial coincides with a report by the Mayo Clinic that an eight-week placebo-controlled, crossover design trial shows no efficacy for black cohosh in treating hot flashes.3 This trial studied 132 women and found no difference compared to placebo. The study treated women with black cohosh for four weeks and used a generic black cohosh product that, according to the authors, they procured under the assumption that it duplicated Remifemin. Presented at the American Society of Clinical Oncology in Orlando, Florida (May 13-17, 2005), the study was funded by a grant from the National Cancer Institute. By my scorecard, that makes two poorly designed trials on black cohosh funded by the U.S. government to date—the other being an eight-week trial completed at Columbia University with women with a history of breast cancer, many taking tamoxifen.4
Conclusion
The results of this clinical trial suggest that 40 mg/d of black cohosh extract safely and effectively treat symptoms associated with menopause with the most significant effect being on hot flashes. This is the first trial to suggest that duration of menopause and baseline FSH levels may be predictors of the efficacy of black cohosh. The results suggest that women with symptoms for one year or less and with a lower baseline FSH are more likely to benefit from black cohosh therapy than women with a longer duration of symptoms and higher baseline FSH.
References
1. Wuttke W, et al. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo- controlled study: Effects on menopause symptoms and bone markers. Maturitas 2003;44(Suppl 1):S67-S77.
2. Levitsky J, et al. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005;50:538-539.
3. Study finds black cohosh no better than placebo in treating hot flashes [press release]. Scottsdale, AZ: Mayo Clinic; May 17, 2005.
4. Jacobson JS, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19: 2739-2745.
Brown D. Black cohosh extract effectively treats climacteric symptoms--best results in early menopause. Altern Ther Women's Health 2005;7(9):69-71.
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