Medicines Q&As
Q&A 364.3
What are the safety concerns surrounding the use of black
cohosh?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Date prepared: 1st November 2012
Background
The extensive media interest surrounding the safety of hormone replacement therapy (HRT) has
meant that many women are considering other options for control of menopausal symptoms. Many
herbal medicines and dietary supplements have been actively marketed as remedies for menopausal
symptoms1,2.
Black cohosh (Cimicifuga racemosa L. Nutt) is a coarse perennial woodland herb native to North
America, where it has been traditionally used by native American Indians for the treatment of various
ailments, including menstrual and menopausal problems 1,3.
The mechanism of action of black cohosh is not well understood. It appears to exert an oestrogenic
effect, although studies have shown that it does not act directly on oestrogen receptors 3.
There have been several concerns raised about the safety of black cohosh, in particular
hepatotoxicity.
This Medicines Q&A assesses and summarises the available evidence regarding safety concerns of
black cohosh.
Answer
Herbal medicines which are unlicensed or that are not regulated under the MHRA’s Traditional Herbal
Registration scheme are not subject to specific standards of safety or quality. The amount of active
constituents in herbal products is subject to variation depending on factors such as parts of the plant
used, growing and harvesting conditions, and methods of extraction 4,5. Long term safety of black
cohosh is unknown; some studies have evaluated use of the herb for up to a year, but most research
is limited to 6 months treatments 3.
Interactions
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Because of the lack of information available about herbal medicines, lack of a documented interaction
does not necessarily mean none exists; it may just mean that the possibility of an interaction has not
yet been studied 2. A summary of possible interactions with black cohosh may be found in table 1.
Table 1. Interactions of black cohosh 3,4
Interaction
Hepatotoxic drugs and
herbal medicines
Severity
High
Onset
Unknown
Likelihood
Possible
Management
Avoid combinations
Substantiation
Theoretical
Tamoxifen
High
Unknown
Unknown
Avoid
Atorvastatin
High
Delayed
Possible
Avoid concomitant
use
Poor- in vitro
research
Poor-One case
report
Cisplatin
High
Unknown
Possible
Avoid
Animal research
Immunosuppressants
High
Unknown
Possible
Avoid
CYP2D6 substrates
Moderate
Unknown
Possible
Avoid
Poor- One case
report with
confounders
Conflicting
Notes
May be increased risk of
liver failure and hepatitis in
combination with other
hepatotoxic drugs and
herbal medicines
An enhanced effect of
tamoxifen may occur.
Elevated LFTs with the
combination, which
resolved on dechallenge.
This may be due to
inhibition of CYP3A4
enzymes
Black cohosh may
decrease effectiveness of
cisplatin
See details below
Black cohosh may inhibit
CYP2D6 enzymes,
although evidence is
conflicting.
Cancer
Conflicting evidence surrounds whether or not black cohosh has oestrogenic activity. If it does act on
oestrogen receptors, there is a risk that it may negatively affect hormone sensitive cancers. In vitro
animal studies suggest that black cohosh may increase the risk of metastasis in women with preexisting breast cancer 3,6.
Due to the lack of clear safety data, women with a history of breast or other hormone sensitive
cancers should avoid use of black cohosh 3.
Transplantation
One case report describes an acute kidney transplant rejection in a patient who was taking black
cohosh and alfafa supplements. Alfafa supplements may have immunostimulating effects, so may be
more likely to have induced the rejection than black cohosh. Although causality of the transplant
rejection has not been established, it would be prudent for patients who have undergone
transplantation, or who are taking immunosuppressant medications, to avoid black cohosh until
further information is known about its use in this patient group 3,4,7.
Liver disease
Several case reports describe hepatotoxicity, many of which required liver transplantation. Due to the
potentially serious nature of this adverse reaction, the use of black cohosh should be discouraged,
especially since liver failure can develop suddenly. Patients who still decide to take black cohosh
should have regular liver function tests 3.
One case report describes a 54 year old woman who presented with acute severe hepatic failure after
8 months of taking a black cohosh supplement. She required a liver transplant and died whilst
undergoing the operation due to uncontrollable haemorrhage 8. In other cases, jaundice and deranged
LFTs have developed following use of black cohosh for menopausal symptoms, requiring
transplantation 9.
Reports of hepatotoxicity have also been received through national pharmacovigilance schemes
worldwide, including the MHRA’s Yellow Card Scheme 9,10. Although causality has not been
established through these case reports, and many have methodological limitations, these reports
have prompted the MHRA to recommend that warnings regarding the possibility of hepatotoxicity
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should be added to products containing black cohosh11. Use of black cohosh is contra-indicated in
patients with pre-existing liver disease 3,9. Teschke et al has recently assessed the likelihood of
causality based on published case reports and spontaneous reports by applying the liver-specific
CIOMS (Council for the International Organisation of Sciences) assessment scale. In each study they
found a lack of causality in all cases and inadequate reporting of confounding factors 12,13,14.
Firenzuoli et al conducted a survey of 107 patients who had undergone 12 months continual
treatment with black cohosh. The study found no signs of hepatotoxicity or hepatic disease in any of
the participants 15.
A meta-analysis of randomised, double blind controlled trials found no clinically significant effects on
liver enzymes in five trials with a total of 1,117 women who had been treated with isopropanolic black
cohosh extract 16. The trials included in the meta analysis were of 3 months or 6 months duration.
In October 2012, the MHRA released a statement reminding the healthcare professionals and the
public of the risk of liver failure with black cohosh remedies. This was in response to a serious case of
liver failure resulting in a liver transplant. The MHRA reiterated the importance of selecting a
registered product and ensuring that patients read the information leaflets and consult a qualified
healthcare professional prior to taking a black cohosh product 17.
Protein S deficiency
There is a theoretical risk that black cohosh may increase risk of thrombosis in patients with protein S
deficiency 3. This is dependent on black cohosh having oestrogenic effects. One case report
describes a patient suffering retinal vein thrombosis following use of a product containing black
cohosh, although causality was not established due to the presence of other herbal extracts in the
product18.
Pregnancy and Lactation
Traditionally, black cohosh has been used to induce labour. There is, however, insufficient available
data to justify its use in this manner 9,19.
One case report describes the use of a mixture of blue and black cohosh for induction of labour in a
previously uneventful pregnancy. The child was born with low apgar scores and no spontaneous
breathing which resulted in hypoxia, acute necrosis and seizures. The quality of the report was limited
by lack of detail regarding the product used and a reliance on animal studies to suggest the clinical
activity of the herbs 4,9.
Theoretically, the possibility of oestrogenic effects may result in an increased risk of miscarriage.
There is, however, insufficient data to suggest this may be the case 4. This lack of data on the use of
black cohosh during pregnancy means that its use should be avoided during pregnancy 9.
There is no data available about levels of black cohosh in breast milk, or any reports of paediatric
concerns caused by breast feeding, although there is a theoretical risk that its oestrogenic activity
may reduce lactation. Because of this lack of safety data, Black cohosh preparations should not be
recommended in lactating women 4,20.
For more information on the use of herbal medicines in breast-feeding women, see Medicines Q&A
93.3 Is it safe for breast feeding women to take herbal medicines?
Adverse effects
Side effects reported on use of black cohosh include GI upset, cramping, rash, headache, dizziness,
weight gain, and peripheral and facial oedema, which appear to occur rarely, (less than 1 in 1000, but
more than 1 in 10,000 patients) 4,21.
Very rarely, breast tenderness, and vaginal spotting may occur.
Liver disorders and deranged LFTs are reported as a rare side effect (see above) 4,20.
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Other reports of adverse reactions include: seizures, asthenia and muscle damage, cutaneous
pseudolymphoma, cutaneous vasculitis and endometrial hyperplasia 4,9. Bradycardia, coagulation
activation, and fluid retention have also been linked with black cohosh use in the literature 22,23.
Summary
Black cohosh is a herbal product commonly used for relief of menopausal symptoms. There are a
number of safety concerns surrounding use of black cohosh, but because of limited and poor quality
data, many concerns remain theoretical. In addition to this, as herbal products are subject to
variations in quality, safety and efficacy, their use should not be recommended routinely.
PRODIGY guidelines state that the use of complementary medicines for control of menopausal
symptoms is not recommended, and if these products are being used, the following advice should be
given:
 The efficacy of these products has not yet been established.
 There is very little control over the quality of the products available, which may vary considerably.
 Some of these treatments (ginseng, black cohosh, and red clover) have oestrogenic properties
and should not be used in women with contraindications to oestrogen (e.g. breast cancer)
 Long-term safety (e.g. effects on the breast and endometrium) has not been assessed.
 Some treatments may have serious adverse effects (e.g. liver toxicity has been reported with
black cohosh and kava)24
Limitations
This Q&A considers only the safety concerns of black cohosh. It does not take into account in detail
the efficacy data, which would need to be considered when treatment decisions are being undertaken.
The amount of good quality information available about herbal medicines is often limited due to the
lack of regulation of these products. Many of the safety concerns are theoretical or are based on case
reports only.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
 Q&As are believed to accurately reflect the medical literature at the time of writing.
 The authors of Medicines Q&As are not responsible for the content of external websites and
links are made available solely to indicate their potential usefulness to users of NeLM. You
must use your judgement to determine the accuracy and relevance of the information they
contain.
 See NeLM for full disclaimer.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drugs and Therapeutics Centre
Date Prepared
1st November 2012
Checked by
Sarah Smith, Regional Drugs and Therapeutics Centre
Date of check
1st November 2012
Search strategy
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Medicines Q&As
Embase: Cimicifuga Racemosa /ae
/ct
/it
Medline Cimicifuga
limit to: humans
limit to: /ae
*Cimicifuga AND *drug interactions
NeLM
ALTMEDEX
MHRA
Natural Medicines Database
PRODIGY Guidelines
References
1
Mahady GB, Fabricant D, Chadwick LR et al. Black Cohosh: An Alternative Therapy for
Menopause?. Nutr Clin Care 2002; 5(6): 283-289
2 NHS Knowledge Service. Behind the Headlines: Dangers of herbal cures. NHS Choices 2009
accessed via http://www.nhs.uk/news/2009/01January/Pages/Menopauseherbalremedies.aspx on
25/10/10.
3 Natural Medicines Comprehensive Database: Black cohosh. 3120 West March Lane, PO Box 8190,
Stockton, California. Accessed via http://naturaldatabase.therapeuticresearch.com/home.aspx?cs= on
25/10/10.
4 ALTMEDEX ® system: Hammerly M, Koffler K, Marray M et al: Black Cohosh. In: Klasco RK (Ed):
ALTMEDEX system (electronic version). Thomson Micromedex, Greenwood Village, Colorado USA.
Available at: http://www.thomsonhc.com . Cited 25/10/10
5 Herbal Medicines Regulation and Safety. The Medicines and Healthcare Products Regulatory
Authority. Accessed via
hhttp://www.mhra.gov.uk/Howweregulate/Medicines/Herbalmedicines/index.htm on 25/10/10.
6 Davis VL, Jayo MJ, Ho, A et al. Black Cohosh increases metastatic mammary cancer in transgenic
mice expressing c-erbB2. Cancer Res 2008: 68(20): 8377-8383
7 Light TD and Light JA. Acute Renal Transplant Rejection Possibly Related to Herbal Medications.
Am J Transplant 2003: 3(12): 1608-1609.
8 Lynch CR, Folkers ME, and Hutson WR. Fulminant Hepatic Failure Associated with the Use of Black
Cohosh: A Case Report. Liver Transplantation 2006; 12: 989-992.
9 Cohosh, Black In: Herbal Medicines. [online] London: Pharmaceutical Press. Accessed via
http://www.medicinescomplete.com/ on 25/10/10.
10 MHRA: Cimicifuga: Drug Analysis Print. Accessed via
http://www.mhra.gov.uk/Onlineservices/Medicines/Druganalysisprints/index.htm on 25/10/10.
11 Press Release: MHRA action on safety concerns over black cohosh and liver injury. MHRA 2006.
12 Teschke R, Schwarzenboeck A, Schmidt-Taenzer et al. Herb-induced liver injury presumable
caused by black cohosh: A survey of initially of purported cases and herbal quality specifications.
Annals of Hepatology 2011; 11(3): 249-259
13 Tescke R, Schmidt-Taenzer W, Wolff A. Spontaneous reports of assumed herbal hepatotoxicity by
black cohosh: is the liver unspecific Naranjo scale precise enough to ascertain causality?
Pharmacoepidemiology & Drug Safety. 2011; 20(6): 567-582
14 Teschke R. Black Cohosh and suspected hepatotoxicity: inconsitencies, confounding variables, and
prospective use of a diagnostic causality algorithm. A critical review. Menopause 2010; 17(2): 426440
15 Firenzuoli F, Gori L, and di Sarsina P. Black Cohosh Hepatic Safety: Follow-up of 107 Patients
Consuming a Special cimicifuga racemosa rhizome Herbal Extract and Review of Literature. Evidence
Based Complementary and Alternative Medicine 2008; doi: 10.1093/ecam/nen009.
16 Naser B, Schnitker J and Minkin M et al. Suspected black cohosh hepatotoxicity: no evidence by
meta-analyisis of rendomised controlled clinical trials for isopropanolic black cohosh extract.
Menopause 2011; 18(4): 366-375
17 Liver Failure case highlights need to use black cohosh remedies carefully. Medicines and
Healthcare Products Regulatory Agency Press Release 29/10/2012 Accessed via
http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON199545 on 01/11/2012
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18
Lai Cheong JE and Bucknall R. Retinal Vein Thrombosis Associated with a Herbal Phytoestrogen
Preparation in a susceptible Patient. Postgrad Med J 2006; 82(964) 135.
19 Murray T and Safranek S. Do any folk remedies or herbals help induce labour? The Journal of
Family Practice 2008; 57(8): 542-544.
20 Hale, TW. Black Cohosh. In: Medications and Mother’s Milk [online version]. Hale Publishing, Texas
USA. Accessed via http://medsmilk.com/html/contact.html on 25/10/10.
21 Summary of Product Characteristics- Menopret (Black Cohosh). Bionorica SE. Accessed via
http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con090787.pdf on 25/10/10
[date of revision of the text 09/06/2010]
22 McKenzie S and Rahman A. Bradycardia in a patient taking black cohosh. Medical Journal of
Australia 2010; 193(8): 479-481
23 Zimmermann R, Witte A, Voll R et al. Coagulation activation and fluid retention associated with the
use of black cohosh: a case study. Climacteric 2010; 13(2): 187-191
24 PRODIGY (2012) Menopause. Accessed via
http://prodigy.clarity.co.uk/menopause/management/scenario_managing_the_menopause_without_hr
t/management_without_hrt on 9th August 2012
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