|
A trial conducted collaboratively by the North Central Cancer Treatment Group and the Mayo Clinic, published in the June 20 issue of the Journal of Clinical Oncology, found that a black cohosh (Actaeae racemosa, syn., Cimicifuga racemosa) rhizome extract made specifically for this controversially-designed study did not reduce hot flashes in post-menopausal women.1 However, this trial has multiple design flaws and limitations, as noted in a press release from the American Botanical Council (ABC) in May of 2005, after an abstract of the research was presented and publicized at a conference.2,3
For this randomized, double-blind, placebo-controlled crossover study, 132 postmenopausal women were asked to complete a daily hot flash diary for 9 weeks.1 Participants were given no treatment during the first week, to generate baseline data. During the next 4 weeks, participants were randomly given either a black cohosh capsule (containing 20 mg black cohosh rhizome extract standardized to contain 1 mg of triterpene glycosides, supplied by Hi-Health Corporation, Scottsdale, AZ) or a placebo (not described) twice per day. For the crossover design, the women received the other therapy (i.e., they crossed over, the placebo group receiving black cohosh and vice versa) during the following 4 weeks. The researchers tried to base their dosage and standardization of black cohosh on the commonly marketed product Remifemin®, which at the time was being imported into the U.S. by GlaxoSmithKline (GSK), Research Triangle Park, NC, and is now imported by Enzymatic Therapy, Greenbay, WI. They were unable to use Remifemin for the trial (see below).
Patients in both groups reported small decreases in hot flash scores over the first 2 weeks of treatment, which then stabilized over the remainder of the trial, including the cross-over period. During treatment with both black cohosh and placebo, there was no significant decrease in any of the parameters of the Green Climacteric Scale and no reported difference in overall quality of life. After treatment, and while still blinded, patients were asked which treatment they preferred; 32% chose black cohosh; 37% chose placebo; and 31% did not prefer either treatment. The authors conclude that “black cohosh most likely has a central neurologic effect (suggested to be dopaminergic) as opposed to a hormonal one,” and they recommended that women try other alternatives for treatment of menopausal symptoms instead of black cohosh.
ABC sent out a press release in May of 2005 commenting on the trial’s results, which had been released at a meeting of the American Society of Clinical Oncology that month but were then unpublished.2 ABC pointed out that trial participants were given black cohosh for only 4 weeks, which, based on previous clinical experience and designs of published clinical trials on black cohosh, is most likely too short a period of time to adequately measure any effect, especially since most clinical trials on black cohosh have run for 3 to 6 months. It was also emphasized that many clinical trials on black cohosh support its safety and efficacy in treating symptoms of menopause. This is particularly true of trials of Remifemin®, which has demonstrated safety and efficacy in numerous studies, including a larger and longer trial than that conducted by Pockaj et al.3 ABC concluded that black cohosh preparations have a long history of beneficial use for menopausal symptoms and that such benefits are supported by multiple trials, all of which contradict the recently published trial.2
According to ABC Founder and Executive Director Mark Blumenthal, “It is curious and highly unusual that this trial design was given a green light for funding by the National Institutes of Health. There is no evidence in the published clinical trial literature that black cohosh preparations can produce a measurably positive effect on menopausal symptoms in the relatively short period of 4 weeks. Even though the authors of this trial have described it as having been an “eight-week” trial, because of its crossover design, it is really 2 four-week trials carried out back to back. As such, it may be viewed as an interesting experiment, i.e., to determine if a heretofore untested black cohosh preparation can produce positive effects on menopause symptoms within 4 weeks, but that’s about all it’s worth,” he added.” Plus, Blumenthal emphasized that the black cohosh preparation used in this trial was not equivalent to any black cohosh preparations in the North American marketplace, having been produced specifically for this trial. “Thus, he added, the results of this trial do not have any bearing on any previously tested black cohosh preparation, nor probably to any commercially available black cohosh product, which women normally use for far longer than 4 weeks.”
Comments on the black cohosh preparation used in the trial
The authors of this trial had previously published a smaller trial in which Remifemin (the leading researched black cohosh preparation) had been used, with a positive outcome.4 However, when they reportedly approached GSK and Remifemin’s manufacturer in Germany, Schaper & Brümmer, they reportedly declined to provide Remifemin for the trial due to their recognition that under the proposed 4-week crossover design, the Remifemin would not produce positive results. That is when the researchers attempted to have a third party produce what they intended to be an analogous black cohosh extract, even though there are significant doubts that such an extract could be readily produced.
More specifically, according to Prof. Dr. Eckehard Liske, Head of International Medical Department at Schaper & Brümmer, the analytical tests mentioned in the clinical trial publication are “only useful for a general description of black cohosh products and not for the purpose for demonstrating a pharmaceutical equivalence of different products, i.e., Remifemin® versus the black cohosh product Pockaj et al. used in their clinical trial.” [Liske E. Blumenthal, July 5, 2006.] Further, Dr. Liske elaborated on the testing methodology: “…their detection wavelength is unsuitable for quantifying triterpene glycosides or cimicifugic acids. Thus the ratio between these two groups of efficacy-relevant compounds, which would be characteristic for each product cannot be established. Production and analysis of raw and intermediate materials of Remifemin® are highly standardized processes which not only keep the product quality as high as possible but which also fine-tune several parameters contributing to the product's efficacy. And due to this, an exact comparison with other black cohosh products is to some extent not possible. We know that our product shows in clinical trials that it is effective and very well tolerated. We don’t know the extraction medium Pockaj et al used. We don’t know the genuine drug-to-extract-ratio being an important indicator of effectiveness and selectivity of the extraction process.”
Finally, it is curious that the study was conducted using a capsule formulation but, strangely, the authors describe that they dissolved tablets to perform the analytical comparison.
-Courtney Cavaliere
References
1. Pockaj B, Gallagher J, Loprinzi C, Stella P, Barton D, Sloan J, Lavasseur B, Rao R, Fitch T, Rowland K, Novotny P, Flynn P, Richelson E, Fauq A. Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG trial N01CC. Journal of Clinical Oncology. 2006;24:2836-2841.
2. Research on black cohosh supports benefits in menopause, herb science group shows weaknesses of new unpublished study [press release]. Austin: American Botanical Council; May 17, 2005.
3. Mayo clinic researchers report on effectiveness of treatments for hot flashes [press release]. Scottsdale, AZ: Mayo Clinic; May 15, 2005.
4. Pockaj BA, Loprinzi CL, Sloan JA, et al: Pilot evaluation of black cohosh for the treatment of hot flashes in women. Cancer Invest. 2004;22:515-521.
|