How It Works
Bottom Line: There is still no conclusive evidence that black cohosh is effective for menopausal symptoms.
It is not clear if black cohosh is beneficial for menopausal symptoms due to conflicting results from various studies. There is not enough evidence to support its anticancer effects in humans. Although black cohosh is generally safe, a few cases of liver failure have been reported from its use.
Purported Uses
Menopausal symptoms
Various studies yielded conflicting results about use of black cohosh for menopausal symptoms
To ease painful or heavy menstruation
No clinical trials have evaluated this use.
Premenstrual syndrome (PMS)
No clinical trials have evaluated this use
As a sedative
No scientific evidence supports this use.
Hot flashes
Clinical trial results are mixed.
Research Evidence
Menopausal symptoms
Most studies on black cohosh have been done in Europe using the German product Remifemin®.
A recent study in Poland compared low (39 mg/day) and high (127 mg/day) dose Remifemin® in 149 menopausal and postmenopausal women with moderate to severe symptoms. After twelve weeks, the low dose was just as effective as the high dose in relieving menopausal symptoms and depression. In addition, this product appeared not to have an estrogenic effect, since it did not stimulate vaginal cell growth or change the women's blood levels of female sex hormones. Studies of longer duration may be helpful.
In another study of menopausal symptoms, 60 healthy women were divided into three groups. Group 1 received 40 drops twice a day of black cohosh (Remifemin®); Group 2 received 2 mg of diazepam (Valium®) daily; and Group 3 received hormone replacement therapy (HRT). Symptom reduction in the three groups was similar. After three months the black cohosh group showed a significant decrease of menopausal symptoms.
The manufacturer of Remifemin® conducted a trial of 152 women with a moderate degree of menopausal symptoms. One group received black cohosh (Remifemin®) two tablets twice a day and the other group received 1 tablet twice a day. In both groups menopausal symptoms improved significantly by the same amount. However, this trial lacks a true control group (receiving a placebo pill) with which to compare the effects seen with Remifemin®.
After twelve weeks in a randomized controlled study of 80 menopausal women, those taking black cohosh extract (Remifemin®) experienced notable improvements in symptoms compared to women taking either hormone replacement therapy (HRT) or a placebo pill. The number of hot flashes dropped from an average of 5 daily to 3.5 in the estrogen group and to less than 1 in the black cohosh group. These results suggest that Remifemin® may be even more effective than HRT in reducing menopause symptoms, but this study did not follow the women long-term to determine if Remifemin® is safer than HRT.
Hot flashes from breast cancer treatment
A randomized, controlled trial studied the effect of black cohosh on hot flashes in women who had finished breast cancer treatment. Forty-two women received black cohosh and 43 received a placebo pill twice a day for 2 months. Fifty-nine women were receiving treatment with tamoxifen as well. The black cohosh and placebo groups reported similar improvements in symptoms, although women taking black cohosh had a greater decrease in sweating. From these data alone, it cannot be determined whether black cohosh is an effective treatment of hot flashes. In addition, this study did not follow patients long-term to determine whether black cohosh is safe in estrogen receptor-positive (ER+) breast cancer patients.
Another randomized, controlled trial also studied the effect of black cohosh on hot flashes in premenopausal women who had finished breast cancer treatment and were undergoing tamoxifen therapy. 46 patients received tamoxifen and 90 women received tamoxifen as well as black cohosh for twelve months. Comparing the two groups, the researchers found that significantly more women receiving black cohosh were free of hot flashes and that women receiving black cohosh had significantly fewer severe hot flashes than those on tamoxifen alone.
Warnings
This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Black cohosh should not be confused with blue cohosh.
Precaution: It is still quite controversial whether or not black cohosh possesses estrogenic activity. This product should be used under the supervision of a physician.
Do Not Take If
You currently have, or have been treated for, an estrogen receptor-positive (ER+) cancer (It is still unclear whether black cohosh acts in the same manner as estrogen, and might therefore stimulate growth of these tumors).
You are taking hormonal medications such as birth control pills (If black cohosh has estrogen-like activity, it will interfere with these medicines).
Side Effects
Stomach upset
Liver failure
Special Point
Because it is still unclear whether black cohosh has estrogenic effects, women with estrogen receptor-positive (ER+) cancers should avoid this supplement.
Scientific Name
Cimicifuga racemosa
Common Name
Black snakeroot, rattlesnake root, squawroot
Brand Name
Remifemin®, Menofem®, Klimadynon®
Clinical Summary
Obtained from root of the plant. Black cohosh is used to palliate the symptoms of menopause and dysmenorrhea. Whether black cohosh has estrogenic activity is under debate; caution should be used in patients with hormone-sensitive disease. Black cohosh alone (7) (10) or in combination with St. John's Wort (18) has been shown to be effective in treatment of menopausal symptoms but conflicting data suggest no such potential (24). It was also shown to have antiosteoporotic effects (19). Studies evaluating black cohosh to treat hot flashes in women after breast cancer treatment yeilded mixed results (8) (15) (17). It should be noted that most studies reported were conducted with the brand-name product Remifemin® that is standardized to contain 1 mg of 27-deoxyacteine. Black cohosh was shown to increase the toxicity of chemotherapy drugs, including doxorubicin and docetaxel in vitro (13). It also increased the incidence of metastatic disease in mice (14). Another study reported presence of CYP3A4 inhibitors in Black cohosh (16). It can therefore interact with medications that are metabolized by the CYP3A4 enzyme. Several cases of hepatic failure have been reported from use of black cohosh (20) (21) (22).
Purported uses
- Dysmenorrhea
- Menopausal symptoms
- Premenstrual syndrome
- Sedation
Constituents
Triterpene glycosides (actein, 12-acetylactein and cimigoside)
Tannins
Isoflavone: Small amounts of formononetin (may not be present in commercially available formulations)
Other constituents such as acetic acid, butyric acid, formic acid, isoferulic acid, palmitic acid, salicylic acid, racemosin, phytosterols, cimicifugin 15-20%
(1)
Mechanism of Action
Black cohosh may have estrogenic effects but there are conflicting data
(6). Studies also showed that it has no effect on LH, FSH, prolactin or estradiol
(2). A black cohosh extract was shown to have antiproliferative and antiestrogenic effects in ER negative cells. This suggests that black cohosh mediates its effects via an estrogen independent pathway
(23).
It is unknown whether or not it has a cardiovascular effect. Black cohosh increases the incidence of metastatic disease in mice
(14).
Warnings
Black cohosh should not be confused with blue cohosh.
Precaution: It is still quite controversial whether or not black cohosh possesses estrogenic activity. This product should be used under the supervision of a physician
Adverse Reactions
(Oral): Gastrointestinal upset
Reported (Oral):Hepatotoxicity has been reported following use of black cohosh (20) (21) (22).
Herb-Drug Interactions
Tamoxifen: Black cohosh may haven an additive antiproliferative effect.
Chemotherapy drugs: Black cohosh may increase the toxicity of doxorubicin and docetaxel
(13).
Cytochrome P450 3A4: Black cohosh may interact with drugs that are metabolized by CYP3A4 enzyme
(16).
Literature Summary and Critique
Pockaj BA, et al. Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG trial N01CC. J Clin Oncol 2006;24:2836-41.
One hundred and thirty-two women with persistent hot flashes for at least one month were randomized to receive 20mg of black cohosh extract twice a day or placebo for four weeks. This was followed by a crossover period of four more weeks where women who initially received black cohosh were given placebo and vice versa. Participants maintained weekly diaries of symptoms including nausea, excessive sweating, chills, headache, nervousness etc. At the end of the study period, women who received black cohosh reported a 20% reduction in the hot flash score compared to a 27% decrease by women on placebo.
These data suggest that black cohosh is not superior to placebo in reducing hot flashes.
Liske E, et al. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Women Health Gend Based Med 2002;11:163-74.
A randomized, double-blind, parallel group study conducted at four clinics in Poland. 149 peri- and postmenopausal women with moderate to severe symptoms received either Remifemin 39 mg/day (n=74) or 127.3 mg/day (n=75) for 12-24 weeks. The high-dose group tended to have more perimenopausal women, but all other characteristics were comparable. Kupperman Menopause Index and Self-Rating Depression Scale improved significantly in both groups; both doses were tolerable. Both doses caused a slight but insignificant increase in vaginal cell proliferation, karyopyknotic index, and eosinophilic index, from which the authors infer a lack of estrogenic effect of Remifemin. No changes in levels of E
2, LH, FSH, PRL, or SHBG were found in postmenopausal women. Studies of longer duration may be helpful.
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;19:2739-45.A prospective, randomized, double-blind evaluation of black cohosh extract on hot flashes in women who had completed primary breast cancer treatment. Patients were stratified based on concurrent tamoxifen treatment and instructed to take 1 tablet of black cohosh (n=42) or placebo (n=43) twice daily for 2 months. Primary outcome measured was change in frequency and intensity of hot flashes. Serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were also measured. Patients receiving black cohosh did have a statistically significant decrease in sweating, but all other symptom improvements were similar between treatment groups. No significant increases in FSH or LH were noted. Of the adverse events reported, none were attributed to black cohosh. Additional studies are required to assess the safety of black cohosh in patients with breast cancer.
Duker EM, et al. Effects of extracts of Cimicifuga racemosa (Remifemin) on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420.An open-label controlled comparative trial of 110 female patients was conducted to evaluate estrogenic activity of
Cimicifuga racemosa. In Group 1 (n=55), patients received 8 mg of extract daily for 8 weeks, while Group 2 (n=55) received placebo for 8 weeks. The results showed a significant LH reduction in the placebo group. No significant change in FSH concentrations was noted in either group. The authors concluded that cimicifuga (Remifemin) possesses estrogenic activity but, unlike estrogens, does not affect the release of prolactin and follicle-stimulating hormone. Researchers then fractionated the extract into three distinct types of active compounds based upon ability to reduce LH secretion in ovariectomized rats and to compete in vitro with 17-beta estradiol for estrogen receptor binding sites. They concluded that the LH suppressive effect of cimicifuga is caused by at least three different synergistically acting compounds.
Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas. 2003 Mar 14;44 Suppl 1:S59-65.
A study of 136 premenopausal women receiving tamoxifen after successful breast cancer treatment. 46 women received tamoxifen alone while 90 women received both tamoxifen and Menofem ® / Klimadynon ®, which corresponds to 20 mg of herbal drug for 12 months. After intervention, no women in the tamoxifen-only group were free from hot flashes, while 47% of the intervention group were free from hot flashes. In addition sever hot flashes were reported in 74% of the tamoxifen-only group and only 24% in the intervention group. Researchers conclude that black cohosh appears to reduce the number and severity of hot flashes caused by tamoxifen treatment.
References
- Newall C, et al. Herbal Medicines, A Guide for Health Care Professionals. London: Pharmaceutical Press; 1996.
- Liske E, et al. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Ther 1998;15:45.
- Anon. Remifemin: A Plant-based Gynecological Agent. Scientific Brochure. Schaper & Brümmer. Germany: 1997.
- Blumenthal et al. Herbal Medicine Expanded Commission E Monographs. Austin: American Botanical Society; 2000.
- Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50.
- Zierau O, et al. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002;80:125-30.
- Liske E, et al. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Women Health Gend Based Med 2002;11:163-74.
- 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;19:2739-45.
- Liske E, et al. Therapy of climacteric complaints with C. racemosa: herbal medicine with clinically proven evidence. Menopause 1998;5:250.
- Schaper and Brummers. Remifemin: A plant based gyn agent, Scientific Brochure, 1997. Germany.
- Duker EM, et al. Effects of extracts of Cimicifuga racemosa (Remifemin) on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420.
- Stoll W, et al. Phytopharmacon influences atrophic vaginal epithelium. Double-blind study: Cimicifuga vs. estrogenic substances. Therapeuticum 1987;1:23.
- Rockwell S, Liu Y, HIggins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005;90(3):233-9.
- Davis V, et al. Effects of Black Cohosh on Mammary Tumor Development and Progression in MMTV-neu Transgenic Mice. Abstract. Proceedings of the AACR, Vol 44, 2nd ed., July 2003.
- Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas. 2003 Mar 14;44 Suppl 1:S59-65.
- Tsukamoto S, Aburatani M, Ohta T. Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa). Evid Based Complement Alternat Med. 2005 ;2(2):223-26.
- Pockaj BA, et al. Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Black Cohosh in the Management of Hot Flashes: NCCTG Trial N01CC1. J Clin Oncol 2006;24(18):2836-41.
- Uebelhack R, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107(2):247-55.
- Wuttke W, et al. Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Menopause 2006; 13(2):185-96.
- Levitsky J, et al. Fulminant liver failure associated with the use of black cohosh. Digestive Diseases and Sciences 2005;50(3):538-39.
- Cohen SM, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11(5):575-77.
- Lontos S, et al. Acute liver failure associated with the use of herbal preparations containing black cohosh. MJA 2003;179(7): 390-91.
- Garita-Hernandez M, Calzado MA, Caballero FJ, et al. The growth inhibitory activity of the Cimicifuga racemosa extract Ze450 is mediated through estrogen and progesterone receptors-independent pathways. Planta Med 2006:72(4):317-23.
- Newton KM, Reed SD, LaCroix AZ, et al. Treament of vasomotor symptoms of menopause with black cohosh, mutibotanicals, soy, hormone therapy, or placebo. Ann Intern Med 2006;145:869-879.
