This cancer information summary provides an overview of the use of black cohosh as a treatment in breast cancer patients and survivors, generally for the relief of symptoms or side effects. The summary provides a brief history of black cohosh research, the results of laboratory and clinical trials, and possible side effects of black cohosh use.
This summary contains the following key information:
Native to eastern and midwestern North America, black cohosh (Actaea racemosa, also known as Cimicifuga racemosa) [
Various types of extracts of black cohosh roots and rhizomes have been studied for their chemical composition and biological activity. Lipophilic extracts have predominantly been used in laboratory studies and only infrequently in clinical trials.[
Several of the chemical constituents of black cohosh extracts have biological activities that have been demonstrated through in vitro studies and are candidate markers for the observed in vivo and clinical effects. Triterpene glycosides have structures similar to steroids,[
Other chemical constituents of black cohosh extracts include aromatic acid phenolpropanoids related to caffeic and ferulic acid, along with the black cohosh-specific fukinolic acid.[
Various plants that resemble black cohosh have been mistakenly or intentionally included in some commercial black cohosh products or plants. Such adulteration can be detected by methods such as microscopy, high-performance thin-layer chromatography, high-performance liquid chromatography ultraviolet, and DNA barcoding.[
Black cohosh root, rhizome, and associated preparations have gained considerable international market and consumer interest for more than 60 years, particularly gaining U.S. interest within the last 15 years.[
Companies distribute black cohosh as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval of such supplements by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. The FDA can remove dietary supplements from the market that are deemed unsafe. Because dietary supplements are not formally reviewed for manufacturing consistency, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved the use of black cohosh as a treatment for cancer or any other medical condition.
Black cohosh was in use by American Indian or Alaska Native people when Europeans arrived in the New World.[
Europeans have used black cohosh to treat menopausal symptoms for over 50 years. In Germany, the Commission E approved black cohosh as a treatment for dysmenorrhea, menopausal symptoms, heart palpitations, nervousness, irritability, sleep disturbances, tinnitus, vertigo, perspiration, and depression.[
Various sources suggested that the recommended dose of crude drug is 40 mg per day.[
Mechanism of Action
Given the apparent clinical effects of black cohosh on menopausal symptoms, early preclinical investigations searched for an anticipated estrogenic activity. These research studies demonstrated differences between lipophilic extracts, which often had evidence of estrogenic activity,[
Considering the recent discovery of nitrogenous black cohosh constituents,[
Mechanism of Action, Pharmacokinetics, Pharmacodynamics
Given that the clinically utilized hydrophilic extracts of black cohosh roots and rhizomes are not estrogenic, alternative mechanisms of menopausal symptom relief have been proposed, one of which suggests serotonergic activity by triterpenes to minimize episodes of hot flashes and bone loss.[
The maximum-tolerated dose and PK of 23-epi-26-deoxyactein, the most abundant triterpene found in the plant,[
Although case reports suggested connections between the use of dietary supplements containing black cohosh and liver damage, no evidence of hepatotoxicity—or any other form of serious toxicity—was found in systematic reviews of results from clinical trials of a chemically standardized black cohosh preparation; regardless of dosage administered, no liver function markers were altered.[
Reports of hepatic adverse effects include one case of acute liver failure, two cases of hepatitis (without further description), and two cases indicating mild elevation of liver function markers, though many of these patients were taking multiple botanical products simultaneously.[
Acute toxicity of black cohosh is also purported to occur through interactions with pharmaceutical agents.[
Prevention of Breast Cancer/Recurrence
Observational studies of postmenopausal women without a history of breast cancer indicated no significant association between the use of black cohosh and development of the disease when compared with nonuse (hazard ratio = 1.17; 95% confidence interval [CI], 0.75–1.82; adjusted odds ratio [OR], 0.80; 95% CI, 0.63–1.00).[
One study suggested a possible protective effect. This case-control trial evaluated whether the use of hormone-related supplements, including black cohosh for the management of menopausal symptoms, was associated with cancer risk or protection.[
Recurrence -free survival was also evaluated as a primary endpoint measure in a sample of breast cancer patients and survivors (n = 18,861), 1,102 of whom had received a product containing a black cohosh extract (i.e., Remifemin® or Remifemin® plus; R/R+, a 40% isopropanol black cohosh extract, with or without St. John's wort extract,[
Effect on Menopausal Symptoms
Several studies have investigated black cohosh in treating women suffering from climacteric complaints, including breast cancer patients and survivors.[
Breast Cancer Patients
Observational and open-label studies have demonstrated reductions in the number and severity of hot flashes among breast cancer patients undergoing adjuvant endocrine therapy complemented with black cohosh; however, randomized, double-blind, placebo-controlled clinical trials have failed to demonstrate reductions greater than that seen with placebo.[
Significant declines in hot flash frequency and severity and other menopausal symptoms are reported in a review of observational studies of breast cancer patients and survivors taking Remifemin® (20–40 mg/d), with or without tamoxifen or raloxifene.[
Statistically significant reductions in hot flash symptomology have also been observed in open-label administration of another black cohosh product, CR BNO 1055 from Bionorica in Germany (40 mg/d), in breast cancer survivors who received adjuvant therapy with tamoxifen; however, double-blind studies so far have failed to show this to be a specific effect.[
Thus far, two randomized, placebo-controlled, double-blind clinical trials have assessed the efficacy of black cohosh use (one trial used black cohosh extract;[
One randomized clinical study specifically evaluated the preventative effect of Remifemin® on symptoms of menopause syndrome (MPS) in breast cancer patients who received luteinizing hormone-releasing hormone analogs (LHRH-a).[
Given these conflicting results in observational and randomized clinical trials, a large placebo effect is presumably at play, especially considering the subjective nature of many of the endpoint measures.[
The efficacy of black cohosh supplementation on vasomotor symptoms has also been evaluated in noncancer populations; however, these findings to date remain inconsistent.
At least two meta-analyses have addressed questions about the specific effect of black cohosh supplements versus placebo. The first meta-analysis [
A comprehensive review of clinical trials that studied the use of black cohosh in noncancer menopausal and/or aging women was published in 2014. The review demonstrated that the overall heterogeneity of clinical evidence was due to major variation in exact intervention materials and clinical endpoints.[
Similarly, the Herbal Alternatives for Menopause (HALT) study investigated the effect of black cohosh (CimiPure®, 70% ethanol extract standardized to 2.5% triterpene glycosides, 160 mg/d) and an encapsulated multibotanical-containing black cohosh (ProGyne; black cohosh, 200 mg/d, along with nine other ingredients),[
Randomized controlled investigations of black cohosh used as monopreparations [
Management of Other Conditions
Bone mineral density
The therapeutic effects of black cohosh on bone metabolism have also been investigated as a secondary outcome measure in a randomized, double-blind clinical trial, comparing results to that of conjugated estrogens (CE) and placebo.[
|Reference||Trial Design||ConditionTreated||No. of Patients: Enrolled; Treated; Placebo or No Treatment Controlb||Primary Outcome||Concurrent TherapyUsed||Level of EvidenceScorec|
|KMI = Kupperman Menopausal Index; LHRH-a = luteinizing hormone-releasing hormone analogs; OR = odds ratio.|
|a For additional information and definition of terms, see text and theNCI Dictionary of Cancer Terms.|
|b Number of patients treated plus number of patient controls may not equal number of patients enrolled; number of patients enrolled equals number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated equals number of enrolled patients who were given the treatment being studied AND for whom results were reported.|
|c For information about levels of evidence analysis and scores, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.|
||Randomized, double-blind, placebo-controlled, crossover trial||Hot flashes||131; 66; 65 (crossover in treated and placebo groups)||No difference in hot flashes from black cohosh compared with placebo after 8 weeks of treatment (primary outcome)||Varioushormonal therapies||1iC|
||Randomized, double-blind, placebo-controlled trial||Hot flashes||85; 42; 43||No difference in the number of hot flashes from placebo at 57 to 60 days||Tamoxifen||1iC|
||Randomized controlled trial||Menopausal symptoms||85; 42; 43||Menopausal symptoms (measured by KMI) significantly lower in patients treated with black cohosh||LHRH-a||1iiC|
||Randomized, double-blind, placebo-controlled trial||Bone metabolism||62; 20 (black cohosh), 22 (conjugated estrogens); 20 (placebo)||Statistically significant increase in bone-specific alkaline phosphatase level||Unknown||1iC|
||Retrospective case-control||Breast cancerprevention||101; 25; 76||Statistically significant OR (0.47) for developing breast cancer in women who took black cohosh supplements||Various therapies||2Di|
||Observational retrospective cohort||Breast cancer recurrence||18,861; 1,102; 17,759||Did not promote breast cancer recurrence or inhibit thetherapeuticeffect of tamoxifen||Tamoxifen||2Di|
In general, the hydroalcoholic black cohosh extracts that are widely used as components in commercially available products—and those used in clinical trials —have been very well tolerated, producing rare serious adverse effects, which are likely due to product quality issues (adulteration) rather than black cohosh itself. An overview of the adverse events from a systematic review of the results of several clinical trials, postmarketing surveillance studies, case series, and case reports found only rare serious adverse events that may not have been induced by black cohosh.[
A small number of studies have explored the potential for black cohosh extracts to interfere with the metabolism or activity of drugs. One group studied the in vivo effect of black cohosh extracts on cytochrome P450 enzymes at doses up to 1,090 mg bid (0.2% triterpene glycosides) and found only weak inhibition of CYP2D6 [
To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
The Committee on Herbal Medicinal Products of the European Medicines Agency describes black cohosh products as a medicine that may be used for the treatment of menopausal symptoms, based on their assessment of the results of around 20 clinical trials involving over 6,000 patients who received black cohosh.[
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text about the results of a meta-analysis that compared the effect of oral black cohosh monopreparations with that of the control group. Subjects in the control group were given red clover, fluoxetine, or placebo. Also added text about the results of a second meta-analysis that included six different randomized controlled trials and investigated the efficacy of a single formulation of black cohosh in reducing climacteric symptomology in perimenopausal and postmenopausal women (cited Castelo-Branco et al. as reference 17).
Added text to state that a comprehensive review of clinical trials that studied the use of black cohosh in noncancer menopausal and/or aging women was published in 2014. The review demonstrated that the overall heterogeneity of clinical evidence was due to major variation in exact intervention materials and clinical endpoints (cited Geller et a. as reference18). Variability in study results are possibly because of differences in extract preparation methods, potentially affecting the concentration of alkaloid constituents, which have not been previously studied in in vitro and clinical research. Other factors that contributed to the heterogeneity included doses administered and study group characteristics.
Renamed Table 1 title from Clinical Studies of Black Cohosh to Clinical Studies of Black Cohosh in Patients With Cancer.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of black cohosh in people with cancer.. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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Levels of Evidence
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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Black Cohosh. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/black-cohosh-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2022-06-07
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