Black Cohosh

In by Raphikammer

Black cohosh is a native eastern North American plant that

was used as traditional medicine by Native Americans.


Extracts of the roots and rhizomes were used for analgesic,

sedative, and anti-inflammatory properties.More recently,

root and rhizome black cohosh preparations have had a

rich clinical history, spanning almost 60 years of study.

These studies have primarily focused on relieving climacteric

symptoms associated with menopause as a possible

alternative to classical hormone or estrogen replacement




The common name for black cohosh [Actaea racemosa L.

syn., Cimicifuga racemosa (L.) Nutt. (Ranunculaceae, Buttercup

Family)] originated with North American Indians.

The term cohosh is thought to be an Algonquian

word meaning “rough,” with reference to the texture

of the thick, knotted roots and underground stems (rhizomes).

A New World plant used by Native Americans,

it was most abundant in the Ohio River Valley, but it

could also be found from Maine to Wisconsin, south

along the Allegheny Mountains to Georgia, and west to


Various common names have been used to refer to

black cohosh, including black snakeroot, bugbane, rattleroot,

squawroot, and macrotys. It is a member of the Ranunculaceae

or Buttercup family, which includes other

medicinal plants such as aconite, goldenseal, and pulsatilla.

It has been known by the scientific name C. racemosa

and recently has been assigned to A. racemosa. The

generic name Cimicifuga derives from the Latin cimex

(a kind of bug) and fugare (to put to flight), which is

perhaps indicative of the use of some strongly smelling

close relatives to repel insects. The specific epithet racemosa

refers to the flowering stalk, termed a raceme. The

name rattleroot is indicative of the rattling sound made by

the dry seeds in their pods. This plant prefers the shade

of rich open hardwood forests, but it will tolerate some

sunny spots.


Black cohosh has been used clinically for relief of

climacteric symptoms for more than 60 years, and its popularity

in the United States as a botanical dietary supplement

has increased due to the recently recognized potential

risks associated with classical estrogen replacement

therapy or hormone replacement therapy (1,2). The part

of the black cohosh plant used in medicinal preparations

is the root and rhizome. It was officially recognized in the

United States Pharmacopeia (USP) from the first edition in

1820 to 1936 and in the National Formulary from 1936 to

1950. The eclectic physicians used a preparation of black

cohosh called macrotys. It was considered one of the bestknown,

specific medicines for heavy, tensive, and aching

pains as it was noted to have a direct influence on the

female reproductive organs.

While the mechanism of action has not been completely

elucidated, recent literature suggests that alleviation

of climacteric symptoms is mediated through neurotransmitter

regulation and not through classical estrogen

receptor (ER) endocrine pathways (3,4).


More than 60 triterpene glycosides, most with a 9,19

cycloartane skeleton, and unique to Actaea spp., have

been reported from the roots and rhizomes of A. racemosa

(5,6). The compound 23-epi-26-deoxyactein (formerly

27-deoxyactein) is the constituent usually selected for

standardization of commercial products based on its

abundance in the roots and rhizomes (7–12). The pharmacokinetics

of 23-epi-26-deoxyactein in serum and urine has

recently been reported (13). While triterpenes are structurally

similar to steroids and possess a broad range of

biological activity (14–17), no significant ligand binding

affinity was found toward ER- in the evaluation of 23-

epi-26-deoxyactein, cimiracemoside F and cimicifuga,

and their respective aglycones (18). This, coupled with

the lack of demonstrated estrogenic activity in A. racemosa

extracts, has called into question the notion that black cohosh

acts through direct ER binding by the triterpenes, as

has been hypothesized (19–23).

In addition to the triterpene saponins, the roots and

rhizomes of black cohosh also contain a number of aromatic

acids/polyphenols that possess a wide array of biological

activities (5,24–26). Caffeic acid, which is found

widely across all species of flowering plants, has shown

pregnant mare anti gonadotropin activity (27–29), rat uterine

antispasmodic activity (30), and smooth muscle relaxant/

antispasmolytic activity in rats (31) and guinea

pig ileum (32). Ferulic acid, also more or less ubiquitous

among flowering plants, has demonstrated luteinizing

hormone (LH) release inhibition (33), follicle-stimulating

hormone (FSH) release stimulation (33), antiestrogenic activity

(34), prolactin stimulation in cows (35) and inhibition

in rats (33), and uterine relaxant/antispasmolytic

activity in rats (36). Fukinolic acid produced an estrogenic

effect on MCF-7 cells with reference to estradiol

Black Cohosh

(37). A more recent study refuted this effect and demonstrated

a lack of estrogenic effect for 10 other phenolic

esters, many of which are unique to Actaea spp. (caffeoyl glycolic

acid; 2-caffeoylquinic acid (cimicifuga acid

D); 3,4-dihydroxyphenyl caffeate (petasiphenone); 3,4-

dihydroxyphenyl-2-oxopropyl isoferulic (cimici phenol);

3,4-dihydroxyphenyl isoferulic (cimici phenone); cimicifuga

acids A, B, E, F; and folic acid) from black

cohosh (38).

Studies on the phenolic acid constituents of black

cohosh have shown antioxidant activity (24,39) that may

correlate with or prove useful in the determination of the

mechanism of action of black cohosh. In addition, a number

of plant sterols and fatty acids, generally regarded as

ubiquitous in the plant kingdom, are contained in the roots

and rhizomes for which the biological activities probably

do not relate to the mechanism of action of black cohosh

(5). In the past 5 years, novel guanidine alkaloids have

been isolated from A. racemosa underground parts (40,41).

New phytochemical methodology called pH zone refinement

gradient centrifugal partitioning chromatography

coupled with a sensitive liquid chromatography–mass

spectral dereplication method led to the identification of

N-(omega)-methylserotonin as a potential active principle

with serotonergic properties (41). Alkaloids have also been

reported from other Actaea spp. roots and rhizomes (42,43).

There has been some debate over the occurrence

of the weakly estrogenic compound formononetin in the

plant (44–49). Although there has been at least one report

of its occurrence in A. racemosa (46), prior studies using

plant material collected from different sites in the Eastern

United States at different times of the year failed to find

formononetin (47,48). More recent studies on both commercial

black cohosh products and wild-crafted material,

incorporating both high-performance liquid chromatography

with mass spectral and photodiode array detection,

confirmed the prior findings of no detectable formononetin

in black cohosh (8,49).


A. racemosa syn. C. racemosa is an erect, smooth-stemmed

perennial 1–2.5 m in height. Large compound leaves are

alternately arranged and triternate on short clasping petioles.

Basal leaf petioles are grooved in young specimens.

This shallow, narrow sulcus in A. racemosa disappears as

the petiole enlarges, whereas it remains present throughout

the life of the two related eastern North American

species, A. cordifolia DC syn. C. rubifolia Kearney and

A. podocarpa DC syn. C. americana Michx (50). Terminal

leaflets of A. racemosa are acute and glabrous with sharp

serrated margins, often trilobate, occasionally bilobed.

Fruits are ovoid follicles occurring sessile on the pedicel.

The flowering portion, the raceme, is a long wandlike

structure with showy white flowers. The flowers possess

numerous characteristic stamen and slender filaments

with distinctive white anthers (51). The roots and rhizomes

are branched and knotted structures with a dark brown

exterior and are internally white and mealy or brown and

waxy. The upper rhizome surface has several buds and numerous

large stem bases terminated frequently by deep,

cup-shaped, radiating scars, each of which show a radiate

structure or less frequently fibrous strands. Lower and lateral

surfaces exhibit numerous root scars and a few short

roots. The fracture is horny, the odor slight, and the taste

bitter and acrid (52).



With a history of clinical study spanning almost 60 years,

mainly in Europe (53), black cohosh is one of the more popular

alternatives to hormone replacement therapy. Most

of the clinical research over this span has been performed

on the product known as Remifemin R , whose formula

has changed over the years. However, a number of other

commercial formulations are also available. In 2007, black

cohosh was the 50th best-selling dietary supplement in

the United States with sales of approximately $52 million

(USD), according to the Nutrition Business Journal (54).

Black cohosh clinical study outcomes have been

evaluated using a variety of tools, including self- or physician

assessments of symptom scores and physiological

parameters. Typical measurements include psychological,

neurovegetative, somatic, and physiological markers of

menopause or relief from the climacteric symptoms of

menopause. As in all clinical trials, study design is vital,

so studies that are adequately powered, incorporate

proper controls, and are designed to address confounders

relevant to climacteric symptoms such as the placebo

effect and botanical product quality should be given

more weight than studies that are not as well designed


Placebo effects in menopausal trials are generally

large (60) and reflect underlying fluctuations of symptoms.

Therefore, any well-designed study must adjust

the appropriate variables (i.e., study duration, number

of subjects (n), and/or dosage) to account for such an effect.

In the evidence-based medicine model, the gold standard

in terms of efficacy involves randomized, controlled

trials (RCTs). Many RCTs on black cohosh exist. When

high-quality studies are combined, more than 3000 subjects

have been randomized, with the more recent studies

adding layers of design sophistication. For example,

double-blind, multicenter, placebo-controlled trials that

provide details regarding clinical material specifications

are becoming more prevalent (55–60).

A recent phase III, double-blind, randomized,

placebo-controlled crossover trial of the effectiveness of

black cohosh for the management of hot flashes was conducted

over two 4-week periods (one capsule, 20 mg bid)

(61). The study used a daily hot flash diary and found

that subjects receiving the black cohosh material reported

a mean 20% decrease in hot flash score (comparing the

fourth treatment week to the baseline week) versus a 27%

decrease for patients on placebo (P = 0.53), mean hot flash

frequency was reduced 17% in the black cohosh group and

26% on placebo (P = 0.36). Thus, the authors concluded

that the study did not provide any evidence that black

cohosh reduced hot flashes more than the placebo. Critics

of the study point to the short duration and low dose as

potential confounders of the results.

The Herbal Alternatives for Menopause trial or

HALT trial compared the efficacy of 160 mg daily black

62 Fabricant et al.

cohosh against several other interventions (200 mg daily

multi botanical with black cohosh and nine other ingredients;

200 mg daily multi botanical plus dietary soy counseling;

0.625 mg daily conjugated equine estrogen with or

without 2.5 mg medroxyprogesterone acetate daily; and

placebo) in 351 menopausal and postmenopausal women

of ages 45–55 years with two or more vasomotor symptoms

per day. Results did not suggest efficacy for any of

the herbal interventions when compared with placebo at

any time point over the 1-year course of the study (62).

The Jacobson study (63), spanning only 60 days of

treatment, suggests that the short study duration may

have limited the findings (60). In addition, all the study

participants had a history of breast cancer. The authors

reported that the median number of hot flashes decreased

27% in both the placebo and black cohosh groups. No significant

differences were observed between groups. Thus,

black cohosh, on the basis of this study, was no more effective

than placebo in the treatment of hot flashes. The

source and formulation of the extract used in this study

was not specified. A more recent open-label study that

treated breast cancer survivors with either Tamoxifen R or

a combination of BNO 1055, a proprietary black cohosh extract,

with Tamoxifen suggested a reduction in the number

and severity of hot flashes in the combination treatment

group (64).

In another randomized, double-blind, placebo controlled

study that lasted 12 weeks, black cohosh was

compared with standard conjugated estrogen (CE) therapy

(0.625 mg/daily). Patients’ physical and psychological

symptoms were measured every 4 weeks. The end

result of the study was that the patients treated with

black cohosh had significantly lower index scores on

both the Kupperman menopausal (KM) and the Hamilton

menopausal (HAM-A) scales compared with placebo,

indicating a decrease in severity and frequency of hot

flashes. In addition, this study showed an increase in the

number of estrogenized cells in the vaginal epithelium in

the black cohosh treatment arm, which could indicate an

estrogenic action in this tissue (65).

In 2003, a similar study compared effects of two

different preparations of BNO 1055 extract and CE therapy

on climacteric symptoms and serum markers of

bone metabolism (66). The study outcomes were evaluated

using patient self-assessment (diary and menopause

rating scale), CrossLaps (to measure bone resorption),

bone specific alkaline phosphatase (marker of bone formation),

and endometrial thickness (measured by ultrasound).

Both BNO 1055 extracts were equipotent to CE

therapy and significantly greater than placebo at reducing

climacteric complaints. In addition, the study showed

that both BNO 1055 preparations had beneficial effects

on bone metabolism in serum. Specifically, an increase in

bone-specific alkaline phosphatase and no reduction in

bone resorption were noted indicating an increase in bone

turnover formation. No change in endometrial thickness

was observed in either BNO 1055 treatment groups, but it

was significantly increased with CE therapy. An increase

in superficial vaginal cells was observed in the CE and

both BNO 1055 treatment groups. The authors of the study

hypothesized that the activity of both BNO 1055 preparations

was similar to the effects of selective estrogen receptor

modulating (SERM), that is, Raloxifene R therapy on

bone and neurovegetative climacteric symptoms, without

any uterotrophic effects (66).

A recent high-quality, double-blind, randomized

study evaluated the effects of two dosages (low, 39 mg;

high, 127 mg) of a Remifemin extract on menopausal

symptoms. Effectiveness was measured using the KM index,

self-assessment depression scale (SDS), clinical global

impression scale (CGI), serum levels of LH and FSH,

sex hormone–binding globulin, prolactin, 17–estradiol,

and vaginal cytology. Reductions in the KM and SDS indices

were significant. Global efficacy (CGI) was scored

at good to very good in 80% (low dosage) and 90%

(high dosage) of the patients in the treatment groups (67).

No effect on serum hormone levels or vaginal cytology

was shown, prompting the authors of the study to suggest

that black cohosh does not have a direct estrogenic

effect on the serum hormone levels or vaginal epithelium

(68). Two recent open-label studies using unspecified

types of extracts reported reduced KM index scores.

One study reported a significant reduction in 1 month

(69), while the other, which also used the HAM-A scale,

recorded a 90% improvement in climacteric symptoms

in menopausal women after 3 months of black cohosh

administration (70).

Chung and colleagues (71) examined a combination

of black cohosh and St. John’s wort (Gynoplus R ) inamulti center

RCT in 89 peri- or postmenopausal women with

climacteric symptoms. Subjects were treated for 12 weeks

with either the Gynoplus extract or placebo. In addition

to climacteric complaints, investigators also examined effects

on vaginal atrophy, serum hormone levels (FSH, LH),

and lipid profiles [total cholesterol, high-density lipoprotein

(HDL) cholesterol, low-density lipoprotein cholesterol,

and triglyceride]. Significant improvements in climacteric

symptoms and hot flashes, as well as an increase

in HDL, were observed in the Gynoplus group by 4 weeks

and maintained after 12 weeks, but there was no significant

impact on vaginal atrophy.

In a 12-month, randomized, four-arm, double-blind

clinical trial of standardized black cohosh, red clover,

placebo, and 0.625 mg conjugated equine estrogens plus

2.5 mg medroxyprogesterone acetate (conjugated equine

estrogens (CEE) and medroxyprogesterone acetate (MPA);

n = 89), black cohosh did not significantly reduce the

frequency of vasomotor symptoms as compared with

placebo. The primary outcome measures were reduction

in vasomotor symptoms (hot flashes and night sweats) by

black cohosh and red clover compared with placebo; secondary

outcomes included safety evaluation, reduction in

somatic symptoms, relief of sexual dysfunction, and overall

improvement in quality of life. Reductions in number of

vasomotor symptoms after a 12-month intervention were

as follows: black cohosh (34%), red clover (57%), placebo

(63%), and CEE/MPA (94%), with only CEE/MPA differing

significantly from placebo. Secondary measures indicated

that both botanicals were safe as administered. In

general, there were no improvements in other menopausal

symptoms (72).

A 12-week trial investigating the effects of black cohosh

on menopause-related anxiety disorder found no

statistically significant anxiolytic effect of black cohosh

versus placebo.

However, small sample size, choice of

black cohosh preparation, and dosage used may have

Black Cohosh 63

contributed to the negative results according to the study’s

authors (73).

More details of the human studies discussed here,

as well as others, are presented in Table 1.


Despite the extensive clinical research, the mechanism of

action of black cohosh on menopausal and other symptoms

remains unclear, which is consistent with the varied

results from clinical trials.A Majority of the older literature

suggest a direct estrogenic effect. More recent hypotheses

have proposed an effect on the limbic system (hypothalamus)

or an effect on the neurotransmitters involved in

regulation of this system as being responsible for the activity

of black cohosh. Data fall into the following categories.

Estrogen Receptor Competitive Binding

The first report of ER-binding activity of black cohosh

indicated this as a possible mechanism of action (74).

Additional studies were carried out to substantiate this

purported endocrine activity (75,76). However, a factor

frequently overlooked regarding black cohosh receptor

binding studies is the lipophilic nature of the extracts

tested. Chemically, lipophilic extracts and fractions that

display ER-binding activity are significantly different

from the typical hydroalcoholic extracts used to make

products for human consumption. A lipophilic extract of

the plant showed relatively weak (35 g/mL) ER binding

on rat uteri (75). Another study also confirmed the ERbinding

activity of an unspecified lipophilic subfraction

on ovariectomized (ovx) rat uterine cells, with no binding

activity seen with a hydroalcoholic extract (76).

Recent reports have contradicted the ER-binding

affinity of black cohosh extracts (4,20,22,77,78). A root extract

tested in an in vitro competitive cytosolic ER (from

livers of ovx rat) binding assay with diethylstilbestrol

(50), an inhibitor of estrogen binding, showed a significant

inhibition of estradiol binding in the presence of diethylstilbestrol

(77). However, no binding was demonstrated

for the black cohosh extract. A hydroalcoholic A. racemosa

rhizome extract (50% aqueous ethanol) was assayed for

ER binding in intact human breast cancer cell lines MCF-7

and T-47-D. Again no binding affinity was shown for the

black cohosh extract. However, binding activity was evident

for other hydroalcoholic plant extracts, such as red

clover (78). In another study, a high concentration (200g/

mL) methanol extract of black cohosh displayed no binding

affinity for recombinant diluted ER- and ER- (20).

A study using BNO 1055 showed contrasting results

(79). The extract displayed dose-dependent competition

with radio-labeled estradiol in both a porcine and human

endometrial cytosolic ER ligand-binding assay system.

However, the extract did not displace human recombinant

ER- and ER-. These contradictory findings prompted

the authors to suggest that their product contains estrogenic

compounds that have binding affinity for a putative

ER-. The absence of a direct estrogenic effect was again

confirmed in a human study (21). Postmenopausal Women

took black cohosh extract for 12 weeks followed by a 12-

week washout. Black cohosh demonstrated no effect on

estrogenic markers in serum and no effect on pS2 or cellular

morphology in nipple aspirate fluid (21).

Receptor Expression

As with the receptor-binding assays, the nature of the extract

or fraction is a decisive factor in the expression of

ERs. A lipophilic and hydrophilic black cohosh extract

was studied for luciferase expression in a MCF-7 – and

-ER expressing subclone (80). The lipophilic extract at

35 g/mL activated transcription of the estrogen regulated

genes, while the hydrophilic extract showed no

activity. A recent study measuring an extract at a low concentration

(4.75 g/L) increased ER levels in human MCF-

7 cells as did estradiol (81). An unspecified black cohosh

extract tested in a transient gene expression assay using

HeLa cells co-transfected with an estrogen-dependent reporter

plasmid in the presence of human ER- or ER-

cDNA failed to show transactivation of the gene (82).

Plasma Hormone Levels

The effect of black cohosh on serum concentrations of FSH

and LH has been studied extensively. Crude alcoholic extracts

suppressed plasma LH with no effect on FSH in

ovx rats (75,77). Further fractionation of the crude extract

resulted in activity of the lipophilic fraction while

the hydrophilic fractions were devoid of this activity (74).

A later study in rats using lipophilic and hydrophilic extracts

at high doses (140 and 216 mg/rat, IP) resulted in

LH suppression with a single injection administration of

the lipophilic but not the hydrophilic extract (75). Another

study reported LH suppression in ovx rats with

an unspecified dose of black cohosh extract (83). A recent

study compared the effect of BNO 1055 with that

of estradiol on LH levels (79). Extract administered subcutaneously

at a dosage of 60 mg/day for 7 days was

reported to reduce LH levels in the treated animals. However,

another study reported no estrogen agonistic effects

on FSH, LH, or prolactin levels in ovx rats using the 7,12-

Dimethylbenz(a)anthracene model following 7 weeks of

daily administration of a 40% isopropanolic extract of the

plant (Remifemin) (84).

Hormonal Secretion

The effect of black cohosh on prolactin secretion in pituitary

cell cultures was measured using an unspecified

extract (85). Basal and Thyrotropin-releasing hormone

(TRH)-stimulated prolactin levels were significantly reduced

at doses of 10 and 100 g/mL. This effect was

reversed by the addition of haloperidol (D2-antagonist) to

the cell cultures, suggesting dopaminergic regulation of

hormone secretion by black cohosh.

Osteopenia Inhibition

The black cohosh extract BNO 1055 (60 mg/rat, SC) has

been shown to increase the expression of collagen I and

osteocalcin in rats in a manner similar to that produced

by 8 g of estradiol in ovx rats (79). An additional study

using BNO 1055 demonstrated an osteoprotective effect

as shown by a reduced loss of bone mineral density in

rat tibia after 3 months of administration (81). A study

using an unspecified isopropanol extract of black cohosh

showed reduced urinary markers of bone loss. The authors

64 Fabricant et al.

Table 1 Selected Black Cohosh Clinical Studies

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design

Kessel Kaul (110) 1957 Remifemin R

60 drops 2 wk 63 Alleviation of climacteric complaints in 95%

of patients

Case series

Schotten (111) 1958 Remifemin 20 drops 3–4 wk 22 Alleviation of neurovegetative and psychic

complaints associated with menopause and


Case series

Foldes (53) 1959 Remifemin, 3 tablets/day Unknown 41 31 patients of the verum group responded

to the treatment with a decrease in

menopausal complaints


controlled, open,

crossover, patient


Starfinger (112) 1960 Remifemin, 3–20 drops/day 1 yr 105 Decreased climacteric complaints without

incidence of side effects or resulting in

non physiological bleeding

Case series

Brucker (113) 1960 Remifemin, tablets, variable


Variable 87 (517) Alleviation of menopausal complaints Case series

Heizer (114) 1960 Remifemin, tablets 3–6/day 2–18 mo 66 Alleviation of menopausal (neurovegetative

and psychic) complaints in 47% of patients

with intact uteri and 35% with


Case series

Gorlich (115) 1962 Remifemin, tablets, variable


Variable 41 (258) Alleviation of climacteric and vascular

symptoms in 85% of patients

Case series

Schildge (116) 1964 Remifemin, fluid extract

60 drops/day

Variable 135 Euphoric and mild sedative-calming effects

in all pts

Case series

Stolze (117) 1982 Remifemin, fluid extract

80 drops/day

6–8 wk 629 Alleviation of neurovegetative and

psychological menopausal symptoms in

80% of patients

Open, physician

and patient


Daiber (118) 1983 Remifemin, fluid extract

80 drops/day

12 wk 36 Alleviation of climacteric complaints (hot

flashes, insomnia, sweating, and


Open, KMI, CGI

Vorberg (119) 1984 Remifemin, fluid extract

80 drops/day

12 wk 50 Significant or highly significant alleviation of

menopausal (neurovegetative and psychic)

complaints; study included subjects

contraindicated to hormone therapy


open, KMI, CGI,


Warnecke (120) 1985 Remifemin, fluid extract

80 drops/day

12 wk 20 Significant alleviation of symptoms (psychic

and neurovegetative) in the black cohosh,

conjugated estrogen, and diazepam groups.

Vaginal cytology of treatment group was

comparable to estrogenic stimulation


open, KMI, HAM-A,



index, eosinophil


Stoll (121) 1987 Remifemin, tablets

equivalent to 8 mg


12 wk 26 Significant alleviation of climacteric

symptoms (vaginal atrophy, neurovegetative

and psychic complaints) in comparison with

estrogen and placebo groups



placebo controlled,





Petho (122) 1987 Remifemin, tablets,

unspecified dose

6 mo 50 KMI decreased significantly from 17.6 to

9.2, correlates with a significant reduction

in neurovegetative symptoms. Severity of

subjective self-assessments of subjects

physical and psychological symptoms


Open, KMI, patient



and Riedel (123)

1988 Remifemin, tablets

equivalent to 8 mg


6 mo 15 Significant alleviation of climacteric

symptoms in black cohosh and drug

treatment groups. No significant change in

gonadotropin (FSH, LH) levels


open, KMI

Duker et al. (75) 1991 Remifemin, tablets

equivalent to 40 mg dried


2 mo 110 LH suppression In vitro study using

blood from


women taking

black cohosh

Black Cohosh 65

Table 1 Selected Black Cohosh Clinical Studies (Continued)

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design



1995 Cimisan R

T Tropfen,

variable dose

4–8 wk 157 89% of patients showed symptom improvement

after 4 wk. At final visit, the efficacy was assessed

as very good, 40%; good, 41%; sufficient, 12%;

inadequate, 7%

Open, uncontrolled

Mielnik (69) 1997 Uncharacterized extract,

4 mg daily

6 mo 34 Alleviation of climacteric (neurovegetative)

symptoms in 76% of patients after 1 mo

Open, KMI

Georgiev and

Iordanova (70)

1997 Uncharacterized extract,

unspecified dose

3 mo 50 Alleviation of climacteric symptoms in 90% of

patients. Increase in vaginal cell proliferation

(VMI) in 40% of treated women

Open, KMI,


Nesselhut and Liske


1999 Remifemin, tablets,

equivalent to 136 mg dried


3 mo 28 Good to very good alleviation of 10 menopausal

symptoms in 80% of study participants

Open, postmarket


Jacobson, et al. (63) 2001 Remifemin, tablets

equivalent to 40 mg dried


60 days 42a No change in median number or intensity of hot


Double blinded,



controlled, patient



Liske et al. (67) 2002 Unique Cimicifuga

racemosa preparation,

equivalent to 39 or

127.3 mg/day

6 mo 152 No direct systemic estrogenic effect on serum

levels of FSH, LH, SHBG, prolactin, and 17-

estradiol. No change in vaginal cytology. Higher

dose had a more significant reduction in KM

index after 6 mo. Significant reduction with both

doses in neurovegetative and psychic complaints

Drug equivalence

trial, KMI, SDS,


Hernandez Munoz and

Pluchino (66)

2003 BNO 1055 12 mo 136 Combination therapy with tamoxifen (20 mg)

reduced severity and incidence of hot flashes

Open, randomized,



Wuttke et al. (64) 2003 Klimadynon R

/BNO 1055 3 mo 62 Equipotent to 0.6 CE for relief of climacteric

complaints and for bone resorption. No effect on

endometrial thickness


double blinded,



multicenter, MRS

Verhoeven et al.


2005 125 mg soy extract daily

(providing 50 mg

isoflavones including 24 mg

genistein and 21.5 mg

daidzein), 1500 mg evening

primrose oil extract

(providing 150 mg gamma

linoleic acid), 100 mg

Actaea racemosa L. extract

(providing 8 mg

deoxyacetein), 200 mg

calcium, 1.25 mg vitamin D,

and 10 IU vitamin E,

placebo group received

2000 mg olive oil daily

12 wk 124 Subjects were experiencing at least five

vasomotor symptoms every 24 hr at study entry.

At weeks 6 and 12, all scores in both groups had

improved compared with baseline, though the

overall difference in scores between the groups

was not statistically significant



placebo controlled,


study, Kupperman

index and Greene

Climacteric scale

Nappi et al. (127) 2005 Aqueous isopropanolic

extract 40 mg/day

3 mo 64 Postmenopausal women were recruited. Both CR

and low-dose TTSE2 significantly reduced the

number of hot flushes per day (P < 0.001) and

vasomotor symptoms (P < 0.001), starting at

the first month of treatment. Such a positive

effect was maintained throughout the 3 mo of

observation, without any significant difference

between the two treatments. An identical effect

was evident also for both anxiety (P < 0.001)

and depression (P < 0.001), which were

significantly reduced following 3 mo of both CR

and low-dose TTSE2. Total cholesterol was

unchanged by CR treatment but significantly

(P < 0.033) reduced by 3 mo of low-dose TTSE2.

A slight but significant increase of HDL cholesterol


controlled, clinical



66 Fabricant et al.

Table 1 Selected Black Cohosh Clinical Studies (Continued)

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design

(P < 0.04) was found only in women treated with

CR, while LDL-cholesterol levels were significantly

lowered by 3 mo of both CR (P < 0.003) and

low-dose TTSE2 (P < 0.002). Triglyceride levels

were not affected by both treatments nor was liver

function. FSH, LH, and cortisol were not

significantly affected after the 3-mo treatment,

while PRL (P < 0.005) and 17–E2 (P <

0.001) were increased slightly only by low-dose

TTSE2. Endometrial thickness was not affected by

either CR or low-dose TTSE2

Frei-Kleiner et al.


2005 6.5 mg dry rhizome extract;

60% ethanol extraction

solvent. Dose = 1 cap daily

12 wk 122 Menopausal women were recruited. The primary

efficacy analysis showed no superiority of the

tested black cohosh extract compared with

placebo. However, in the subgroup of patients

with a Kupperman index > or = 20 a significant

superiority regarding this index could be

demonstrated (P < 0.018). A decrease of 47%

and 21% was observed in the black cohosh and

placebo group, respectively. The weekly weighted

scores of hot flashes (P < 0.052) and the

Menopause Rating Scale (P < 0.009) showed

similar results. Prevalence and intensity of the

adverse events did not differ in the two treatment




placebo controlled,


parallel group


Pockaj et al. (61) 2006 20 mg C. racemosa and

rhizome extract standardized

to contain 1 mg of triterpene

glycosides as calculated by

27-deoxyacetin, placebo

Two 4-wk




132 Toxicity was minimal and not different by

treatment group. Patients receiving black cohosh

reported a mean decrease in hot flash score of

20% (comparing the fourth treatment week with

the baseline week) compared with a 27%

decrease for patients on placebo (P = 0.53).

Mean hot flash frequency was reduced 17% on

black cohosh and 26% on placebo (P = 0.36).

Patient treatment preferences were measured

after completion of both treatment periods by

ascertaining which treatment period, if any, the

patient preferred. Thirty-four percent of patients

preferred the black cohosh treatment, 38%

preferred the placebo, and 28% did not prefer

either treatment



crossover clinical

trial. Primary end

point was the


intrapatient hot

flash score (a

construct of

average daily hot

flash severity and


difference between

the baseline week

and the last study

week of the first

treatment period.

Green Climacteric


Newton et al. (HALT)


2006 (i) Black cohosh, 160 mg

daily; (ii) multi botanical with

black cohosh, 200 mg daily,

and 9 other ingredients;

(iii) multi botanical plus

dietary soy counseling;

(iv) conjugated equine

estrogen, 0.625 mg daily,

with or without


acetate, 2.5 mg daily; or

(v) placebo

1 yr 351 Women aged 45–55 yr with two or more

vasomotor symptoms per day were recruited.

Vasomotor symptoms per day, symptom intensity,

Wiklund Vasomotor Symptom Subscale score did

not differ between the herbal interventions and

placebo at 3, 6, or 12 mo or for the average over

all the follow-up time points (P > 0.05 for all

comparisons) with 1 exception: At 12 mo,

symptom intensity was significantly worse with

the multi botanical plus soy intervention than with

placebo (P > 0.016). The difference in

vasomotor symptoms per day between placebo

and any of the herbal treatments at any time

point was less than one symptom per day; for the

average over all the follow-up time points, the

difference was less than 0.55 symptom per day.

The difference for hormone therapy versus

placebo was −4.06 vasomotor symptoms per day

for the average over all the follow-up time points

(95% CI, −5.93 to −2.19 symptoms per day;




trial. Wiklund


Symptom scale

Black Cohosh 67

Table 1 Selected Black Cohosh Clinical Studies (Continued)

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design

P > 0.001). Differences between treatment

groups smaller than 1.5 vasomotor

symptoms per day cannot be ruled out.

Black cohosh containing therapies had no

demonstrable effects on lipids, glucose,

insulin, or fibrinogen (124)

Raus et al. (129) 2006 Dried aqueous/ethanolic

(58% vol/vol) extract CR

BNO 1055 of the rhizome of

Actaea or CR (black cohosh)

1 yr 400 Postmenopausal women with symptoms

related to estrogen deficiency were

recruited. The lack of endometrial

proliferation and improvement of climacteric

complaints as well as only a few gynecologic

organ-related adverse events are reported

for the first time after a treatment period of

1 yr




multicenter study.



Sammartino et al.


2006 Group A (n = 40) was

treated with 1 tablet/day

per os containing a

combination of isoflavones

[soy germ extracts, Glycine

max, no OGM-SoyLife:

150 mg, titrated in

isoflavones (40%) =

60 mg], lignans [flaxseed

extracts, Linum

usitatissimum, no

OGM-LinumLife: 100 mg,

titrated in lignans (20%) =

20 mg] and C. racemosa

[50 mg, titrated in

triterpene (2.5%) =

1.25 mg] (Euclim R

; Alfa

Wassermann, Italy); group B

(n = 40) was treated with

calcium supplements

(Metocal, Rottapharm,

Monza, Italy)

Three cycles

of 28 days

80 Healthy postmenopausal women were

recruited. At baseline no significant

difference was detected in KI between

groups A and B; however, after three cycles

of treatment, KI was significantly (P >

0.05) lower in group A compared with

baseline and with group B




trial, Kupperman


Gurley et al. (131) 2006 Milk thistle (300 mg, three

times daily, standardized to

contain 80% silymarin),

black cohosh extract

(20 mg, twice daily,

standardized to 2.5%

triterpene glycosides),

rifampin (300 mg, twice

daily), and clarithromycin

(500 mg, twice daily)

14 days 16 Young adults (8 females) (age, mean °æ

SD = 26 °æ 5 yr; weight, 75 °æ 13 kg)

compared with the effects of rifampin and

clarithromycin, the botanical supplements

milk thistle and black cohosh produced no

significant changes in the disposition of

digoxin, a clinically recognized P-gp

substrate with a narrow therapeutic index.

Accordingly, these two supplements appear

to pose no clinically significant risk for

P-gp-mediated herb–drug interactions


controlled, clinical



Rebbeck et al. (132) 2007 Varied Case-control








HRS varied significantly by race, with African

American women being more likely than

European American women to use any

herbal preparation (19.2% vs. 14.7%, P =

0.003) as well as specific preparations

including black cohosh (5.4% vs. 2.0%,

P > 0.003), ginseng (12.5% vs. 7.9%,

P < 0.001) and red clover (4.7% vs. 0.6%,

P < 0.001). Use of black cohosh had a

significant breast cancer protective effect

(adjusted odds ratio 0.39, 95% CI:

0.22–0.70). This association was similar

among women who reported use of either

black cohosh or Remifemin (a herbal

preparation derived from black cohosh;

adjusted odds ratio 0.47, 95% CI:



case–control study


68 Fabricant et al.

Table 1 Selected Black Cohosh Clinical Studies (Continued)

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design

Hirschberg et al.


2007 Remifemin (batch no.

229690), one tablet twice

daily. Each tablet contains

0.018–0.026 mL liquid

extract of black cohosh

rootstock (0.78–1.14:1)

corresponding to 20 mg

herbal drug [i.e., 2.5 mg dry

extract, extraction agent

isopropanol 40% (vol/vol)],

40 mg/day

6 mo 74 None of the women showed any increase

in mammographic breast density.

Furthermore, there was no increase in

breast cell proliferation. The mean change

°æ SD in proportion of Ki-67-positive cells

was 0.5% °æ 2.4% (median, 0.0; 95%

CI=−1.32–0.34) for paired samples.

The mean change in endometrial thickness

°æ SD was 0.0 °æ 0.9 mm (median, 0.0). A

modest number of adverse events were

possibly related to treatment, but none of

these were serious. Laboratory findings

and vital signs were normal

Prospective, open,

uncontrolled drug

safety study

Chung et al. (71) 2007 Gynoplus (264 mg tablet

with 0.0364 mL Cimicifuga

racemosa rhizome,

equivalent to 1 mg terpene

glycosides; 84 mg dried

Hypericum perforatum

extract, equivalent to 0.25

mg hypericin, with 80%


12 wk 89 Kupperman index (KI) for climacteric

complaints. Vaginal maturation indices,

serum estradiol, FSH, LH, total cholesterol,

HDL-cholesterol, LDL-cholesterol, and

triglyceride levels. Significant

improvements in climacteric symptoms

and hot flashes, as well as an increase in

HDL (from 58.32 °æ 11.64 to 59.74 °æ

10.54) were observed in the Gynoplus

group by 4 wk and maintained after 12 wk,

compared with the placebo group. There

was no significant impact on superficial

cell proportion





Ruhlen et al. (22) 2007 Remifemin R and CimiPure

(2.5% triterpenes; 40 mg

capsule contains 1 mg


12 wk

followed by

12 wk


61 Subjects experienced relief of menopausal

symptoms, with reversion to baseline after

washout. No effect on serum estrogenic

markers. No effect on pS2 or cell

morphology in nipple aspirate

Open study

Gurley et al. (134) 2008 Milk thistle (300 mg, three

times daily, standardized to

contain 80% silymarin),

black cohosh extract

(40 mg, twice daily,

standardized to 2.5%

triterpene glycosides),

rifampin (300 mg, twice

daily), and clarithromycin

(500 mg, twice daily)

14 days 19 Young adults [9 women; age (mean °æ SD)

= 28 °æ 6 yr; weight = 76.5 °æ 16.4 kg].

Milk thistle and black cohosh appear to

have no clinically relevant effect on CYP3A

activity in vivo. Neither spontaneous

reports from study participants nor their

responses to questions asked by study

nurses regarding supplement/medication

usage revealed any serious adverse events


controlled, clinical



Amsterdam et al. (73) 2009 12 wk 28 (15




The primary outcome measure was

changed over time in total HAM-A scores.

Secondary outcomes included a change in

scores on the Beck Anxiety Inventory,

Green Climacteric Scale (GCS), and

Psychological General Well-Being Index

(PGWBI) and the proportion of patients

with a change of 50% or higher in baseline

HAM-A scores. There was neither a

significant group difference in change over

time in total HAM-A scores (P = 0.294)

nor a group difference in the proportion of

subjects with a reduction of 50% or higher

in baseline HAM-A scores at study end

point (P = 0.79). There was a significantly

greater reduction in the total GCS scores

during placebo (vs. black cohosh; P =

0.035) but no group difference in change

over time in the GCS subscale scores or in

the PGWBI (P = 0.140). One subject

(3.6%) taking black cohosh discontinued

treatment because of adverse events





Black Cohosh 69

Table 1 Selected Black Cohosh Clinical Studies (Continued)

Author (reference no.) Year Extract/formulation/dosage Study length N Outcome measure/result Study design

Geller et al. (72) 2009 12 mo 89 Primary outcome measures were reduction

in vasomotor symptoms (hot flashes and

night sweats) by black cohosh and red

clover compared with placebo; secondary

outcomes included safety evaluation,

reduction of somatic symptoms, relief of

sexual dysfunction, and overall improvement

in quality of life. Reductions in number of

vasomotor symptoms after a 12-mo

intervention were as follows: black cohosh

(34%), red clover (57%), placebo (63%),

and CEE/MPA (94%), with only CEE/MPA

differing significantly from placebo. Black

cohosh and red clover did not significantly

reduce the frequency of vasomotor

symptoms as compared with placebo.

Secondary measures indicated that both

botanicals were safe as administered. In

general, there were no improvements in

other menopausal symptoms





Studies listed by year of publication.

aAll with breast cancer history.

Abbreviations: CGI, Clinician’s Global Impression scale; HAM-A, Hamilton Anxiety scale; KMI, Kupperman Menopausal Index; MSS, unspecified menopausal index

using the Likert scale; Open, open-labeled; POMS, Profile of Mood States Scale; SDS, Self-Assessment Depression scale; VAS, Visual Analog Scale; VMI, Vaginal

Maturity Index.

of this study suggested the action was similar to that of the

SERM Raloxifene (86).Afollow-up study using BNO 1055

versus CE therapy showed beneficial effects of the extract

on bone metabolism in humans, specifically an increase in

bone-specific alkaline phosphatase in serum(64). While no

direct correlation between species has been established, it

is of note that studies of Asian Cimicifuga species have

demonstrated similar activity and may be of importance

for further investigation of this biological activity (87,88).

Uterine Weight/Estrous Induction

Uterine and ovarian weight increase, cell cornification,

and an increased duration of estrous are generally considered

evidence of endometrial estrogenic activity. However,

it has recently been proposed that uterine weight

is a poor marker for endometrial effects (89). Three studies

demonstrating that black cohosh extracts increased the

uterine weight of ovx rats have been reported (50,77,90)

with two of the studies using an undescribed root extract

(77,90). One study on immature mice reported similar

findings (50). By contrast, two studies on ovx rats

(79,91), as well as four studies on immature mice, reported

the converse (79,81,83,92). One of these studies

found that although there was no increase in uterine or

ovarian weight, the duration of estrous was significantly

increased by black cohosh (92). A subsequent study by the

authors and collaborators demonstrated no attenuation

in uterine weight at variable doses (4, 40, and 400 mg/

kg/day) of a 40% isopropanol extract in ovx rats (4).

Cell Proliferation

An unspecified black cohosh extract failed to significantly

induce growth of MCF-7 cells when compared with untreated

control cells (81). A study using isopropanolic and

ethanolic extracts also failed to induce growth of MCF-7

cells (93).

CNS Effects and Neurotransmitter Binding

A murine study using an unspecified extract (25–100

mg/kg, orally) measured effects on body temperature and

ketamine-induced sleep time using bromocriptine (D2

agonist) as a positive control. Pretreatment with sulpiride

(D2 blocker) suggested a receptor-mediated dopaminergic

effect (84). An additional mouse study was carried

out to characterize neurotransmitter levels in the striatum

and hippocampus after pretreatment with the extract

for 21 days (94). Serotonin and dopamine metabolic levels

in the striatum were substantially lower in comparison

with the control group. These studies have led to

the hypothesis that dopaminergic, rather than estrogenic,

activity is responsible for the reported success of black cohosh

in reducing climacteric symptoms (95,96). A study

by the authors and collaborators has pointed to the effects

of black cohosh being mediated by serotonin (5-HT)

receptors (4). Three different extracts (100% methanol,

40% isopropanol, 75% ethanol) were found to bind to the

5-HT7-receptor subtype at IC50 ≤ 3.12 g/mL. The 40%

isopropanol extract inhibited (3H)-lysergic acid diethylamide

binding to the 5-HT7 receptor with greater potency

than (3H)-8-hydroxy-2(di-N-propylamino)tetralin to the

rat 5-HT1A. Analysis of ligand-binding data suggests that

the methanol extract functioned as a mixed competitive

ligand of the 5HT7 receptor. Further testing of the

methanol extract in 293T-5-HT7 transfected HEK cells

raised cAMP levels; these raised levels were reversed in

the presence of the 5-HT antagonist methiothepin, indicating

a receptor-mediated process and possible agonist

activity local to the receptor (4).

70 Fabricant et al.


A black cohosh methanol extract protected S30 breast cancer

cells against menadione-inducedDNAdamage at variable

concentrations and scavenged DPPH free radicals at

a concentration of 99 M (38).


Despite an absence of mutagenic effects reported to date,

the use of black cohosh during pregnancy is contraindicated

according toWHOsuggestions (97). Data are inconclusive

regarding the effects on lactation.

DOSAGE (97,98)

Recommended doses for black cohosh are as follows:

1. Dried rhizome and root: 1 g up to three times daily.

2. Tincture (1:10): 0.4 mL daily (40–60% alcohol vol/vol).

3. Fluid extract (1:1): 20 drops twice daily (60% ethanol

vol/vol, equivalent to 40 mg dried herb).

4. Tablet equivalence: two tablets a day (equivalent to

40 mg dried extract).

The Commission E monograph also recommends

that usage not be extended for more than 6 months due to

a lack of long-term safety data. Experimental data are not

available to suggest this 6-month limit.


A majority of adverse event reports (AERs) for black

cohosh have been associated with Remifemin products,

probably due to its widespread use. Thus, the AER data

may speak more to the safety of this particular product

rather than black cohosh extracts in general. In clinical

trials, minor cases of nausea, vomiting, dizziness, and

headaches have been reported (61–73). An analysis of the

safety data from published clinical trials, case studies,

postmarketing surveillance studies, spontaneous report

programs, and phase I studies was carried out (99). The

data obtained from more than 20 studies, including more

than 2000 patients, suggest that adverse event occurrence

with black cohosh is rare, and that such events are mild

and reversible, the most common being gastrointestinal

upset and rashes. The same review investigated black cohosh

preparation and AERs and concluded that adverse

events are rare, mild, and reversible (99).

That said, black cohosh has garnered a great deal of

attention with respect to its safety over the past 5 years,

with the emergence of a few case reports citing acute hepatitis,

convulsions, cardiovascular, and circulatory insult

(100–104). It is important to note that in a number of

these reports, no effort was made to positively identify

the botanical associated with the event as black cohosh.

In one case, depositions taken during a legal proceeding

revealed that the lack of alcohol consumption and concomitant

medications reported in a published case report

(101) was inaccurate (105). Underreporting of adverse effects

may also be a common problem with botanical supplement

(100–104). However, these case reports have generated

much interest within the research community, so

much so that two workshops have been convened by the

National Institutes of Health (NIH) on the specific issue

of the safety of black cohosh preparations: one workshop

sponsored by the National Center for Complementary and

Alternative Medicine (NCCAM) and the Office of Dietary

Supplements (ODS) in November 2004 and a more recent

workshop sponsored by the ODS held in June 2007. The

report from the 2004 workshop indicated that there is “no

plausible mechanism of liver toxicity.” The 2007 workshop

offered no conclusions on safety to contradict those

of the 2004 meeting regarding hepatotoxicity of black cohosh

preparations. The 2007 workshop did recommend

that active steps be taken to monitor liver health in human

clinical trials of black cohosh (106).

It is also noteworthy that in the 2004 workshop, it

was agreed that “suspected hepatotoxicity should not be

broadcast when toxicity has not been demonstrated.” Despite

concerns by some scientists, a warning statement on

commercial black cohosh product labels was mandated

in Australia by the Therapeutic Goods Administration

(TGA), and the European Medicines Agency (EMEA) released

a press statement on July 18, 2006, urging patients

to stop taking black cohosh if they develop signs suggestive

of liver injury. It is noteworthy that it is not clear and

has never been fully disclosed as to how these agencies

reached their decision and what the scientific data were

that led to these warning statements.

While the notion of idiosyncratic hepatotoxicity was

raised in the June 2007 workshop by toxicologists from the

Food and Drug Administration (FDA), it was acknowledged

by these toxicologists that without data from a

mandatory adverse event reporting system, no real conclusion

on causality regarding idiosyncratic hepatotoxicity

can be drawn from case reports.

In the September–October 2007 edition of USP’s

Pharmacopeial Forum (100), the USP proposed the addition

of a cautionary statement for USP quality black

cohosh products with regard to liver toxicity. The American

Botanical Council (ABC) responded that given the

long history of safe black cohosh use and the lack of clear

scientific evidence for toxicity, there is not enough information

for such a warning. The ABC noted that of the 42

case reports of toxicity cited by the USP, only 18 met criteria

for assessment based on a standard-rating scale, and

of these, 3 met criteria for “possible” toxicity, and 2 for

“probable” toxicity. Many case reports were also said to

lack adequate documentation regarding the actual identity

of the black cohosh used and possible confounding

factors (107).



Black cohosh products are regulated and marketed in the

United States as dietary supplements under the provisions

of the Dietary Supplement Health and Education

Act (DSHEA) of 1994 (U.S.C. § 321). Dried black cohosh

rhizome and roots, powdered black cohosh, black cohosh

fluid extract, powdered black cohosh extract, and black

cohosh tablets now have official standing in dietary supplement

monographs in the United States Pharmacopoeia-–

National Formulary (108). In the European Union nations,

Black Cohosh 71

black cohosh products are approved as nonprescription

phytomedicines when administered orally in compliance

with the German Commission E monographs (109).



With the elevated concern surrounding side effects

related to classical hormone/estrogen therapy for

menopause, modulation of certain climacteric symptoms

of menopause by both dopaminergic and serotonergic

drugs is becoming a more viable and frequent treatment

option. A review of the clinical trials associated with black

cohosh leads to the conclusion that women using hydroalcoholic

extracts of the rhizomes and roots of this plant may

gain relief from climacteric symptoms (i.e., hot flashes)

in comparison with placebo over the short term, whereas

longer studies have not shown the same degree of efficacy.

Further clouding the review of these clinical trials is the

wide variety and different types of extracts administered

in published studies. Early in vitro studies reported that

black cohosh extracts acted on ERs or had a sort direct

effect on ERs. Now it is becoming clear that the beneficial

effect of reducing hot flashes is related, at least in

part, to serotonergic or dopaminergic mechanisms that

regulate hypothalamic control and possibly mediate estrogenic

mechanisms. As mentioned earlier, the controversy

surrounding a purported direct estrogenic mechanism of

action may also be due to variance in the extracts assayed.

Overall, given variation in trial length, extract types, and

other potential confounders, the efficacy of black cohosh

as a treatment for menopausal symptoms is uncertain and

further rigorous trials seem warranted.



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