About Herbs, Botanicals & Other Products

Scientific Name
Cimicifuga racemosa
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Common Name

Black snakeroot, rattlesnake root, squawroot

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Brand Name

Remifemin®, Menofem®, Klimadynon®

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Clinical Summary

Obtained from root of the plant, black cohosh is used as a dietary supplement to relieve the symptoms of menopause and dysmenorrhea. Black cohosh has antiosteoporotic effects (8) and has been shown to enhance bone formation (9). Black cohosh alone (1) (2) (3) or in combination with other herbs (4), (5) has been shown in clinical studies to be effective in the treatment of menopausal symptoms, but data are conflicting (6) (31) (32) (36). Studies evaluating black cohosh to treat hot flashes from breast cancer treatment also yielded mixed results (10) (11) (12). Further supplementation with black cohosh did not enhance bone density, menopausal symptoms, or 10-year risk of coronary heart disease in early postmenopausal women (37).

In vitro studies show black cohosh decreases prostate cancer cell proliferation (14) and induces an apoptotic response in liver cells (21). However, it also increased the incidence of metastatic disease in mice (16). Whether it has similar effects in breast cancer patients is not well studied, although a retrospective observational study of breast cancer patients found that black cohosh enhanced disease-free survival (15).

Some studies indiate that black cohosh does not possess estrogenic activity. Until this is confirmed, patients with estrogen receptor-positive cancers should use caution when considering the use of black cohosh dietary supplements.
Hepatoxicity has been assoicated with use of black cohosh (18) (20) (33) (34), but conclusions from a meta analysis contradict such reports (39). Patients should consult their physicians before using black cohosh supplements.

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Purported Uses
  • Dysmenorrhea
  • Menopausal symptoms
  • Premenstrual syndrome
  • Sedation
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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%
    (22)
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Mechanism of Action

Black cohosh may have estrogenic effects, but there are conflicting data (23). Studies also showed that it has no effect on LH, FSH, prolactin, or estradiol (24). 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 (25), possibly through HER-2 signaling (26) It is unknown whether or not it has a cardiovascular effect. Black cohosh increases the incidence of metastatic disease in mice (16).

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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.
  • After reviewing 30 independent cases of reported hepatoxicity associated with black cohosh intake, the United States Pharmacopeia's Botanical Expert Committee decided that black cohosh products should include a statement of caution concerning their use (28).
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Adverse Reactions
  • (Oral): Gastrointestinal upset and rashes are most common followed by dizziness, headaches, nausea, and vomiting when higher than normal doses are taken (27)
  • Reported (Oral): Hepatotoxicity has been reported following use of black cohosh (18) (20) (33) (34).
  • Reported (Oral): Two cases of liver injury resembling autoimmune hepatitis were reported after taking black cohosh. Both patients responded to treatment with corticosteroids (35).
  • Reported (Oral): A case of coagulation activation, fluid retention, and transient autoimmune hepatitis has been reported associated with use of black cohosh(38).
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Herb-Drug Interactions

Tamoxifen: Black cohosh may have 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 (17).

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Literature Summary and Critique

Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment—results of a large-scale, controlled, observational study. Maturitas. Aug 20 2007;57(4):405-414.A prospective, controlled open-label observational study of 6141 women was used to analyze the effect of Black cohosh alone (Remifemin®) or in conjunction with St. John's wort (Remifemin® plus) on menopausal symptoms. After 3 months, the participants' Menopause Rating Scale (MRS) and PSYCHE scores were determined, demonstrating that the menopause-relieving characteristics of black cohosh were enhanced by St. John's wort. However, because of the observational nature of the study, no placebo-controlled group was included.

Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer. Apr 1 2007;120(7):1523-1528.
The relationship between breast cancer risk and hormone-related supplement use, including black cohosh, was assessed in a population-based case-control study of 949 participants with breast cancer and 1524 control participants. Use of either black cohosh or Remifemin® was associated with a reduction in breast cancer risk. Future studies to analyze the putative chemopreventative effects of black cohosh are required.

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.

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References
  1. Anon. Remifemin: A Plant-based Gynecological Agent. Germany: Schaper & Brümmer; 1997.
  2. 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.
  3. Oktem M, Eroglu D, Karahan HB, et al. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther. Mar-Apr 2007;24(2):448-461.
  4. Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107(2):247-55.
  5. Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment—results of a large-scale, controlled, observational study. Maturitas. Aug 20 2007;57(4):405-414.
  6. 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.
  7. Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas. Sep 20 2007;58(1):31-41.
  8. Wuttke W, Gorkow C, Seidlova-Wuttke D. 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.
  9. Chan BY, Lau KS, Jiang B, Kennelly EJ, Kronenberg F, Kung AW. Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells.Bone. May 7 2008.
  10. 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.
  11. Jacobson JS, Troxel AB, Evans J, 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.
  12. Pockaj BA, Gallagher JG, Loprinzi CL, 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.
  13. 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.
  14. Jarry H, Stromeier S, Wuttke W, Nahrstedt A. Petasiphenone, a phenol isolated from Cimicifuga racemosa, in vitro inhibits proliferation of the human prostate cancer cell line LNCaP. Planta Med. Feb 2007;73(2):184-187.
  15. Zepelin HH, Meden H, Kostev K, et al. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther. Mar 2007;45(3):143-154.
  16. Davis VL, Jayo MJ, Ho A, et al. Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2. Cancer Res. 2008 Oct 15;68(20):8377-83.
  17. Tsukamoto S, Aburatani M, Ohta T. Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa). Evid Based Complement Alternat Med. Jun 2005;2(2):223-226.
  18. Cohen SM, O'Connor AM, Hart J, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11(5):575-77.
  19. Levitsky J, Alli TA, Wisecarver J, et al. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci. Mar 2005;50(3):538-539.
  20. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. MJA 2003;179(7): 390-91.
  21. Lude S, Torok M, Dieterle S, et al. Hepatic effects of Cimicifuga racemosa extract in vivo and in vitro. Cell Mol Life Sci. Nov 2007;64(21):2848-2857.
  22. Newall C. Herbal Medicines, A Guide for Health Care Professionals. London: Pharmaceutical Press; 1996.
  23. Zierau O, Bodinet C, Kolba S, et al. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002;80:125-30.
  24. Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Ther. Jan-Feb 1998;15(1):45-53.
  25. 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.
  26. Einbond LS, Wen-Cai Y, He K, et al. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. Jun 2008;15(6-7):504-511.
  27. Low Dog T, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. Jul-Aug 2003;10(4):299-313.
  28. Mahady GB, Dog TL, Barrett ML, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause. Mar 12 2008.
  29. Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer. Apr 1 2007;120(7):1523-1528.
  30. Duker EM, Kopanski L, Jarry H, Wuttke W. Effects of extracts of Cimicifuga racemosa (Remifemin) on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420.
  31. Reed SD, Newton KM, LaCroix AZ, et al. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause. 2008 Jan-Feb;15(1):51-8.
  32. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009 Jul 15. [Epub ahead of print]
  33. Pierard S, Coche JC, Lanthier P, et al. Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution. Eur J Gastroenterol Hepatol. 2009 Aug;21(8):941-5.
  34. Vannacci A, Lapi F, Gallo E, et al. A case of hepatitis associated with long-term use of Cimicifuga racemosa. Altern Ther Health Med. 2009 May-Jun;15(3):62-3.
  35. Guzman G, Kallwitz ER, Wojewoda C, et al. Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh. Case Report Med. 2009;2009:918156.
  36. Shams T, Setia MS, Hemmings R, et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern Ther Health Med. 2010 Jan-Feb;16(1):36-44.
  37. Bebenek M, Kemmler W, von Stengel S, Engelke K, Kalender WA. Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone mineral density, 10-year coronary heart disease risk, and menopausal complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen (TRACE) study. Menopause. 2010 Jul;17(4):791-800.
  38. Zimmermann R, Witte A, Voll RE, Strobel J, Frieser M. Coagulation activation and fluid retention associated with the use of black cohosh: a case study. Climacteric. 2010 Apr;13(2):187-91.
  39. Naser B, Schnitker J, Minkin MJ, et al. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause. 2011 Jan 11. [Epub ahead of print]
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How It Works

Bottom Line: There is some evidence that black cohosh is effective for menopausal symptoms. More research is needed.

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. Patients should use caution as liver failure has been reported from its use.

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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.
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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.

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Patient 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.
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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).
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Side Effects
  • Stomach upset
  • Liver failure
  • Reported (Oral): Hepatotoxicity has been reported following use of black cohosh.
  • Reported (Oral): Two cases of liver injury resembling autoimmune hepatitis were reported after taking black cohosh. Both patients responded to treatment with corticosteroids.
  • Reported (Oral): A case of coagulation activation, fluid retention, and transient autoimmune hepatitis has been reported associated with use of black cohosh.
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Special Point

Because it is still unclear whether black cohosh has estrogenic effects, women with estrogen receptor-positive (ER+) cancers should avoid this supplement.

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Dosage (Inside MSKCC Only)
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Aliases
Cimicifuga Racemosa
Klimadynon®
Menofem®
Remifemin®
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: February 9, 2011