Description
Black cohosh (Actaea racemosa, Cimicifuga racemosa) is a medicinal plant traditionally used for managing menopausal symptoms, particularly hot flushes. It is of clinical interest in women with a history of breast cancer, who may experience treatment-induced menopause.
Efficacy
A systematic review of 14 randomized controlled trials (RCTs), seven uncontrolled trials, and five observational studies as well as a subsequently published RCT have evaluated black cohosh for menopausal symptoms, cancer risk, and hormonal effects in women with a history of breast cancer.
- Menopausal symptoms: Evidence is inconsistent. While uncontrolled (n=2) and observational studies (n=1) suggest symptom relief in women with a history of breast cancer, RCTs (n=4) generally do not show significant benefit over placebo.
- Hormonal effects: Across 13 RCTs and five uncontrolled studies, black cohosh does not alter oestradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, and shows no oestrogenic effects on breast, endometrial, or vaginal tissues.
- Breast cancer Risk: Observational data are mixed; two studies show no impact, and two suggest a potential protective effect. There is no evidence that black cohosh increases risk of breast cancer or recurrence.
Safety
Generally well tolerated short-term, including in cancer patients. Caution is advised in those with liver concerns or hormone-sensitive conditions. Data on long-term use and drug interactions are limited.
Description
Black cohosh (Actaea racemosa, Cimicifuga racemosa) also known as bugbane, black snakeroot, rattle weed) is a medicinal plant from the Ranunculacea family (Leach 2012). Its root or rhizome is used medicinally. Native to eastern North America, it was traditionally used by Native Americans and Europeans for women’s health issues like chronic ovaritis and amenorrhoea (NatMed 2023). It has been widely used in Europe since the 1940s for menopausal symptoms, dysmenorrhoea, and neurovegetative complaints. Today, it's mainly used for hot flushes and other menopausal symptoms (Leach 2012).
Ingredients and quality requirements
The root contains active compounds including triterpene glycosides (acetin, cimicifugoside), fatty acids, caffeic acids, and isoflavones. Extracts are typically ethanolic or isopropanolic and standardized to 2.5%–5% triterpene glycosides (Leach 2012; NatMed 2023).
Alleged indications
Primarily used for menopausal symptoms such as hot flushes, night sweats, sleep problems, and mood changes (Kligler 2003), it is also used for premenstrual syndrome and dysmenorrhoea (Fritz 2014).
Women with breast cancer often experience premature menopause or a worsening of menopausal symptoms due to anti-hormone therapies such as tamoxifen (Fritz 2014). They may consider black cohosh as an alternative to hormone replacement therapy because of evidence of a relationship between long-term use of HRT and increased risk of breast cancer (Roussow 2002), and potential stimulation of cancer growth by HRT (Schairer 2003).
Application and dosage
Black cohosh is a dietary supplement, usually available as tablets. The most common dosage is 40mg daily of a standardized extract of black cohosh (usually standardized to 1mg or 2.5-5% triterpene glycosides) (Kligler 2003). In clinical trials doses ranging from 40mg-160mg/day, administered from 4 weeks to 12 months have been used (Leach 2012).
Mechanism of action
Black cohosh exhibits context-dependent and tissue-specific effects, particularly with relevance to hormone modulation and anticancer activity. (Fritz 2014)
Hormone modulation
- Most clinical studies: No significant changes in oestradiol, follicle stimulating hormone (FSH), or luteinizing hormone (LH).
- Some isolated findings: increased oestradiol or FSH in specific studies. One study showed reduced breast cancer risk; another showed reduced recurrence risk (possibly due to concomitant tamoxifen use).
Black cohosh manifested selective oestrogen receptor (SERM)-like effects (Fritz 2014, NatMed 2024).
- In vitro: Black cohosh downregulates ER-α expression dose-dependently and reduces cell viability, especially when combined with estrogen, ICI, or tamoxifen. (Crone 2019)
- In vivo: Synergistic effect with tamoxifen, increasing tumour-free survival (Ruan 2019).
Anticancer activities
In vitro, black cohosh and its bioactive compounds have shown several anticancer properties (Fatima 2024).
- Whole extract: Cytotoxicity, apoptosis, cell cycle arrest in various cancers (breast, liver, myeloma); enhanced methotrexate cytotoxicity (all in vitro).
- Cimicifugoside: Inhibits nucleoside uptake—may enhance chemotherapy (hypothesized).
- Acerinol: Enhances sensitivity to doxorubicin, vincristine, paclitaxel (in vitro).
- 5-Anhydrocimigenol-xylopyranoside: Induces apoptosis and inhibits hepatoma tumour growth (in vitro).
- Actein & triterpenes: Synergize with paclitaxel, doxorubicin, 5-FU, and trastuzumab (all in vitro).
Legal issues
Black cohosh holds a traditional herbal registration from the European Medicines Agency's Committee on Herbal Medicinal Products for relieving menopausal symptoms like hot flushes, night sweats, and mood changes (HMPC 2018). Under EU law, herbal medicines can be registered as drugs if used medicinally for at least 30 years, including 15 years within the EU (MHRA 2019).
Current clinical research on black cohosh in cancer patients focuses exclusively on breast cancer. A 2014 systematic review remains the most comprehensive source, including 26 studies: 14 RCTs, 7 uncontrolled trials, and 5 observational studies. (Fritz 2014) It evaluated black cohosh’s effect on menopausal symptoms, hormone levels, and breast cancer risk. Only one additional RCT has been published since (Wang 2019). No human studies have investigated its use in other cancer types.
Findings for black cohosh for menopausal symptoms in non-cancer populations will not be reviewed here but are generally similar to those found in cancer populations. (e.g. Castelo-Branco 2021; Leach 2012; Shams 2010).
Description of included studies
Menopausal symptoms
Evidence for black cohosh in managing hot flushes in breast cancer patients is mixed. Improvements in hot flushes were reported for black cohosh in the two uncontrolled trials and the open-label RCT, but there was no significant benefit found in the two placebo-controlled RCTs or the cohort study. All studies used a black cohosh extract (most often Remifemin) at doses of 20-40mg daily for minimum 4-weeks. Study sizes ranged from 23 to 132 women who were pre or post-menopausal with a history of breast cancer, or high risk of breast cancer Participants were often on endocrine therapy (e.g., tamoxifen or aromatase inhibitors).
A 2019 open-label RCT found Remifemin (40 mg/day) with Lutenizing hormone release hormone analogue (LHRH-a) and endocrine therapy (aromatase inhibitor or SERM) significantly reduced menopausal symptoms (Kupperman Menopause Index) in 85 pre/peri-menopausal breast cancer survivors. (Wang 2019) However, due to the lack of placebo control these findings need to be confirmed.
Hormone levels
Seventeen trials (12 RCTs, 5 uncontrolled trials) reviewed in the systematic review showed no significant impact of black cohosh on circulating hormone levels or proliferation in oestrogen responsive tissues (Fritz 2014). Similarly, the 2019 trial found no significant changes in FSH, LH, oestradiol, endometrial thickness, ovarian cysts, or fibroids, however a higher incidence of cervical cysts was reported in the Remifemin group (21.4% vs. 4.7%, p = 0.02).
Breast cancer risk
Three observational studies in the 2014 review examined primary breast cancer risk, with two showing no association and one indicating reduced risk (OR = 0.47; 95% CI: 0.27–0.82) among postmenopausal users. One study found a reduced recurrence risk (HR = 0.75; 95% CI: 0.63–0.89) in survivors, though differences in tamoxifen use may have contributed (35.8% vs. 24%). Negative interaction with tamoxifen appears unlikely. There is no evidence that black cohosh increases risk of breast cancer or its recurrence. (Fritz 2014; Henneicke 2007)
Adverse events
Black cohosh is generally well tolerated. Meta-analyses show low risk of hepatotoxicity (Naser 2011; Castelo-Branco 2021); most liver injury reports lacked clear causality. (Teschke 2009-2011; Huang 2010; Firenzuoli 2011; Mahady 2008).
Reported adverse events in humans are mostly isolated, with unclear or unknown causality (NatMed 2024; Borrelli 2008):
Cardiac/Neurological: Reversible bradycardia, seizure, dyskinesia (with ginseng), mania, light-headedness.
Hepatic: Transient hepatitis, one severe; one autoimmune, resolved after discontinuation; three cases of liver enzyme elevations-resolved after discontinuation. context-related, unknown due to insufficient data.
Breast cancer patients on tamoxifen and black cohosh: Mild side effects (e.g. constipation, vaginal bleeding, weight gain, endometrial changes).
Menopausal patients: Light-headedness, dry mouth, sleep issues, anxiety, pain.
Other: Cutaneous pseudolymphoma, retinal vein thrombosis, allergic conjunctivitis, uterine bleeding, arthralgia/oedema, hyponatraemia (1 case in pregnancy, Blitz 2016).
Contraindications
Pregnancy and lactation: theoretical risk due to hormone modulatory effects of black cohosh (insufficient clinical evidence).
Children: No safety data available.
Hormone-sensitive cancers/conditions: hypothesized risk due to potential oestrogenic modulation. (Fritz 2014, Crone 2019).
Hepatic impairment: Conflicting and insufficient data, context dependent. (NatMed 2024).
Interactions
Interactions are mainly based on limited or inconclusive data with unknown clinical relevance.
Hepatotoxic drugs: hypothesized interactions include hepatotoxic drugs based on possible increased risk of hepatotoxicity reported in human case reports (see Adverse Events section), Unknown: Risk of hepatotoxicity.
Statins: One case report of liver enzyme elevation, reversible. Unclear cause-effect relationship. (NatMed 2024).
Hormonal therapies: dose-dependent decrease in oestrogen receptor-alpha (Erα), and progesterone receptor A/B. Unknown: Risk of reduced efficacy of oestrogen-based therapies-hypothesized (NatMed 2024).
Oxidant chemotherapy:
- Scavenged oxidative species (in vitro) (Burdette 2002)
- Increased efficacy: Doxorubicin, docetaxel (in vitro).
- Decreased efficacy: Cisplatin (in vitro).
- No effect on outcome: Cyclophosphamide, radiation (in vitro).
Unknown: Risk of chemotherapy inefficacy (NatMed 2024).
CYP450 enzymes:
- CYP3A4: Inhibited in vitro (Tsukamoto 2005); not in humans (Gurley 2006. Unclear clinical significance.
- Tamoxifen/raloxifene/aromatase inhibitors: Synergism in humans; (Fritz 2014; interference with tamoxifen (Li 2011). Unknown: drug-drug interaction risk, toxicity increase risk.
P-glycoprotein (P-gp): Black cohosh did not modulate P-gp and did not affect digoxin in a small study including 16 healthy women (Gurley 2005). Unknown: drug-toxicity risk.
Checkpoint inhibitors: Animal data in mice suggest increased cytotoxic T-cell response; clinical relevance unknown. (Smith 2014). Unknown: Risk of enhanced effect/toxicity.
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Citation
CAM Cancer Collaboration. Black cohosh (Actaea racemosa) | CAM Cancer, May 2025.
Document history
Update of “Mechanisms of action” and “Is it safe” sections in April 2025 by Lisa Dal Pozzo; “What is it” and “Does it work” sections by the CAM Cancer Collaboration. Updated literature search in April 2025.
Updated in May 2020 by Ellen Conte. Assessed as up to date in January 2019, March 2017, September 2013 by Barbara Wider. Updated in June 2012 and August 2009 by Jianping Liu, Xun Li and Guoyan Yang. Summary first published in March 2006, authored by Jianping Liu.
Photo: Mostphotos.com
