Black Cohosh and Menopausal Hot Flushes

Abstract & Commentary

By Leon Speroff, MD, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland. Dr. Speroff is a consultant for Barr Laboratories and does research for Wyeth.

Synopsis: Black cohosh, when studied in appropriate randomized trials, is no different than placebo treatment in affecting hot flushing.

Source: Pockaj BA, et al. Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial NO1CC1. J Clin Oncol. 2006;24:2836-2841.

Pockaj and colleagues from the mayo clinic reported the results of a double-blind, randomized, cross-over clinical trial to study the efficacy of black cohosh for the treatment of menopausal hot flushes.1 The studied dose was 20 mg b.i.d. of Cimicifuga racemosa (the dose of the most commonly marketed black cohosh product in the United States, Remifemin). The similarity of the studied product with Remifemin was confirmed by high performance liquid chromatography and proton nuclear magnetic resonance analysis. 132 patients were treated for two 4-week crossover periods. Black cohosh reduced hot flushing scores by 20% in the fourth treatment week compared with 27% in the placebo group; and frequency was reduced 17% on black cohosh and 26% on placebo. The authors concluded that black cohosh had no effect on hot flushing beyond that of a placebo response.

Commentary

Black cohosh is also called black snakeroot and bugbane. It has been heavily promoted, especially by German clinicians, for the treatment of menopausal hot flushes. We have learned that the study of hot flushing requires randomization to placebo treatment because placebo treatment is associated with an average 51% reduction in hot flush frequency.2 Unfortunately, most of the reports supporting the efficacy of black cohosh were case series or studies without placebo control groups or the studies did not directly and quantitatively measure hot flushing.

"Remifemin" is commercially available, as an alcoholic extract of the root. Black cohosh has been reported to contain formononetin, a methylated precursor that is metabolized to the two primary phytoestrogens, genistein and daidzein. More sophisticated analysis, however, using liquid chromatography methods, has failed to detect the presence of formononetin in various black cohosh preparations, nor in black cohosh roots and rhizomes.3

An older clinical trial was noteworthy and alone in finding a similar impact on hot flushing with black cohosh and placebo treatment.4 Finally, recent trials are confirming that early study and providing us with a uniform story. The Herbal Alternatives for Menopause (HALT) Study is centered in Seattle, Washington. This double-blind trial randomized 351 women to placebo or one of 4 treatment groups: (1) black cohosh 160 mg daily (note the higher dose); (2) a multibotanical treatment containing 50 mg black cohosh, alfalfa, chaste tree, dong quae, false unicorn, licorice, oats, pomegranate, and Siberian ginseng, 4 capsules daily; (3) the multibotanical plus counseling to increase dietary soy intake; (4) conjugated estrogens 0.625 mg with or without 2.5 mg medroxyprogesterone acetate.5 After one year, no differences were observed in hot flushing comparing any of the 3 herbal treatment groups to placebo.6 The herbal remedies also had no effect on sleep quality as reported after 3 months.7

How can I say it any more forcefully than this: black cohosh is not estrogenic, and black cohosh has no effect on menopausal symptoms. Thus far, all phytoestrogen products (this includes soy and red clover extracts) are proving to be no different than placebo for treating hot flushes. Estrogen products continue to be the most efficacious for this purpose. The serotonin uptake inhibitor class of antidepressants is the next most effective. There has not been a head-to-head comparison study of estrogen and SSRIs, but it is reasonable to estimate that an SSRI will reduce hot flushing by about 60% compared to 90% suppression with estrogen.

References

1. Pockaj BA, et al. Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial NO1CC1. J Clin Oncol. 2006;24:2836-2841.

2. Maclennan AH, et al. Oral oestrogen replacement therapy versus placebo for hot flushes. Menstrual Disorders Module of the Cochrane Database of Systematic Reviews 2000.

3. Jiang B, et al. Analysis of formononetin from black cohosh (Actaea racemosa). Phytomedicine. 2006;13:477-486.

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;19:2739-2345.

5. Newton KM, et al. The Herbal Alternatives for Menopause (HALT) Study: background and study design. Maturitas. 2005;52:134-146.

6. Newton KM, et al. HALT: Herbal Alternatives for Menopause Study. North American Menopause Society Annual Meeting, Abstract S-13, 2005.

7. Newton KM, et al. The impact of hormone therapy and herbal remedies for menopause symptoms on sleep quality: the HALT trial (7th European Congress on Menopause, Abstract FCO8.5). Maturitas. 2006;54S:S52.