Vol.2 Issue 1
Menopause

I'm a gynecologist and several of my menopausal patients have discontinued their hormone replacement therapy (HRT) in light of the recent findings of the Women's Health Initiative. Some of these patients have begun using black cohosh to manage their symptoms. What's the evidence to support the estrogenic effects of black cohosh and is it a safe substitute for HRT?

Reviews of the data from published clinical trials have concluded that a standardized black cohosh extract (Remifemin® is the only black cohosh product that has been clinically tested) is more effective than placebo for the treatment of hot flashes in healthy women. Thus, the hypothesis that black cohosh is estrogenic was based on the observation that menopausal symptoms occur when estrogen levels decline, therefore anything that relieves menopausal symptoms must be estrogenic. However, data from a number of the clinical trials showed no changes in hormone levels in women treated with a standardized black cohosh extract, and thus do not support an estrogenic theory. Only one clinical study has reported a significant reduction in LH levels in women treated with a black cohosh extract as compared with placebo. However, the methodology used in this investigation was questionable, as baseline measurements were never performed. The latest human study showed no estrogenic effects in menopausal women treated with a standardized black cohosh product (Remifemin®). Furthermore, data from numerous in vitro and in vivo studies with estrogen receptor-positive breast cancer cell lines have shown mixed results. For example, one of the latest studies by a group of German researchers does not support an estrogenic mechanism for black cohosh. This group evaluated the safety of a standardized black cohosh extract (Remifemin®) in ovariectomized female rats to determine the effects of extract on estrogen-receptor positive mammary gland cells, in animals with 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumors. No overt estrogenic effects were observed and treatment with the extract did not stimulate the growth of mammary tumors in these animals. In the few conflicting publications, where estrogenic effects are claimed for black cohosh, there is a problem with the description of the extract. Most of these publications do not describe the type of black cohosh extract used in the investigation, thus putting into question the study outcomes. Quality and standardization issues for herbal preparations are one of the most critical issues in botanical research today, and are still a stumbling block for the botanical industry. How extracts are prepared, in what solvent (ethanol versus petroleum ether), from what part of the plant, proper plant identification and similarity from batch to batch, are all essential pieces of information to any investigation. A poorly defined extract will most likely lead to experimental data that are not reproducible or inconsistent with other investigations. This appears to be the case for black cohosh. Data from studies that used alcohol extracts of the roots/rhizomes of the plant are consistent and do not support an estrogenic mechanism of action for black cohosh. Other mechanisms of action have been suggested, such as effects on neurotransmitters, and research is currently underway in this area.

How this information translates to safety for the consumer is complicated. There are numerous black cohosh products available on the U.S. market today, including many combination products. With the exception of the Remifemin® products, no other black cohosh products have been clinically tested for safety and efficacy. Therefore, to issue a general statement that black cohosh is safe and effective for the treatment of menopausal symptoms would be misleading. As a pharmacist, I believe that consumers should be directed toward products that have some clinical data for safety and efficacy, and at this point in time only recommend the Remifemin® products. Unfortunately, long-term safety studies have not been performed for any of these products, and the longest clinical trial has only been six months. Thus, if menopausal symptoms are so severe that they affect a woman's quality of life, and she cannot or does not want to take estrogens, black cohosh (Remifemin®) is a good alternative. The caveat is that it may take 4 to 6 weeks before the full therapeutic effects are observed and use should be limited to six months.

Gail Mahady, PhD
Assistant Professor
Departments of Pharmacy Practice &
Medicinal Chemistry and Pharmacognosy
University of Illinois at Chicago

References

Borrelli F, Ernst E. Cimicifuga racemosa: a systematic review of its clinical efficacy. Eur J Clin Pharmacol 2002, 58(4):235-41

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.

Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecological disorders. Advances in Therapy, 1998, 15:45-53.

Mahady GB, Fong HHS, Farnsworth NR. Rhizoma Cimicifugae Racemosae. WHO Monographs on selected medicinal plants. Volume II, WHO, Geneva, Switzerland, 2002.

Mahady GB, Fabricant D, Chadwick LR, Dietz B. Black Cohosh: An Alternative Therapy for Menopause? Nutrition in Clinical Care, 2002, 5:283-289.

Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002, 137(10):805-13