Mohammad-Alizadeh-Charandabi et al.

Chinese Medicine 2013, 8:20

http://www.cmjournal.org/content/8/1/20

RESEARCH Open Access

Efficacy of black cohosh (Cimicifuga racemosa L.)

in treating early symptoms of menopause: a
randomized clinical trial
Sakineh Mohammad-Alizadeh-Charandabi, Mahnaz Shahnazi, Jila Nahaee* and Somaei Bayatipayan

Abstract
Background: This study aims to evaluate the efficacy of Black cohosh (Cimicifuga racemosa L.) in treating early
menopausal symptoms.
Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 84 early post-menopausal
participants with Greene climacteric scale (GCS) scores of 15 to 42, who were referred to two public health care centers
in Tehran, Iran, in 2011–2012. The participants were randomly allocated into treatment (6.5 mg of dried extract of Black
cohosh roots daily) and control (placebo) groups with a ratio of 1:1. The participants took one tablet per day for 8 weeks.
The GCS scores were recorded at baseline, and after 4 and 8 weeks of treatment. Data analysis was carried out using a
general linear model with repeated measures with SPSS software. The level of significance was set at P < 0.05.
Results: There was no loss to follow-up during the 8 weeks of treatment. The GCS total score (primary outcome)
in the treatment group was significantly lower than that in the control group at both week 4 [adjusted mean
difference: −7.8 (95% confidence interval: −11.1 to −4.4)] and week 8 [−12.9 (−16.2 to −9.3)]. The treatment group
showed significantly more improvement than the control group in all GCS subscale scores (vasomotor, psychiatric,
physical, and sexual symptoms; secondary outcomes). The differences between the treatment and control groups at
week 8 were significantly higher (P < 0.001) than those at week 4 in terms of the total scores and the vasomotor and
psychiatric subscale scores. No side effects were reported.
Conclusions: Black cohosh reduced the GCS total score and all GCS subscale scores (vasomotor, psychiatric, physical,
and sexual symptoms) during 4 and 8 weeks of treatment.
Clinical trial registration: This study was approved (Code 9061) by the Ethics Committee of Tabriz University of
Medical Sciences and registered at the Iranian Registry of Clinical Trials with IRCT201107186709N4 on 15 January 2012.

Background other sociodemographic variables [5]. In a study in Ilam,

Menopause is the final menstrual period, and occurs Iran, early post-menopausal women suffered vasomotor
at an average age of 51 years [1,2]. The number of symptoms (55%), vaginal dryness and decreased libido
peri-menopausal women is increasing in the world [1]. (43%), and mild anxiety and depression (54%) [6].
Menopause happens because of loss of ovarian activ- Hormone replacement therapy is the standard treatment
ity, and is associated with a number of early and late for early symptoms in post-menopausal women [7], but
symptoms. Early symptoms include hot flashes, insomnia, increases the risks of stroke, heart diseases, and breast
sweating, anxiety, palpitations, headaches, poor concentra- cancer in older women [8,9]. Some studies have shown that
tion, and loss of libido [3,4]. These symptoms usually last the number of post-menopausal women using hormone
for 1 or 2 years after menopause, but may continue up to replacement therapy is low [10] and that the effects of
10 years or more in some women [2]. The symptoms may hormone replacement therapy in reducing menopausal
reduce quality of life, and are independent of age and symptoms are lower than expected [11,12]. For these
reasons, there has been a tendency toward use of alterna-
* Correspondence: jnahaee@yahoo.com tive therapies to relieve menopausal symptoms [13,14].
Midwifery Department, Tabriz University of Medical Sciences, Tabriz, Iran

© 2013 Mohammad-Alizadeh-Charandabi et al.; licensee BioMed Central Ltd. This is an open access article distributed under
the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Mohammad-Alizadeh-Charandabi et al. Chinese Medicine 2013, 8:20 Page 2 of 7
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Black cohosh (Cimicifuga racemosa L.) is an herb and size containing Black cohosh or placebo tablets were
proposed for treatment of menopausal symptoms [15]. used to conceal the allocation and to maintain the
Cimicifuga roots and rhizomes contain triterpene gly- blinding. Every envelope contained 56 pills of Black co-
cosides (e.g., actein, 27-deoxyactein, and cimifugaside) and hosh or placebo. The participants were instructed to
alkaloids (e.g., cytisine and N-methyl cytisine), derivatives take one tablet per day after dinner for 8 weeks.
of phenylpropane (e.g., ferulic acids and isoferulic acids), The envelopes were prepared by a person who was not
and cimicifugine (25–50% of the root components) [15]. involved in the recruitment, data collection, or data ana-
Although the exact mechanisms underlying the effects lysis. Therefore, the researchers and participants were
of Black cohosh have not been determined, its medical unaware of the kind of tablets given to each participant
effects are related to triterpene glycosides [16]. It functions (blinding).
in a serotogenic manner rather than an estrogenic manner The Black cohosh tablets, which were bought from a
[17-19], binds to estrogen receptors, and selectively sup- pharmacy, were in the form of coated tablets. Each tablet
presses luteinizing hormone secretion with no effect on contained 6.5 mg of dried extract of Black cohosh root,
follicle-stimulating hormone [20]. representing 0.12–0.18 mg of 27-deoxyactein. The tablets,
The effects of Black cohosh on early menopausal symp- named Cimifugol, are commercially distributed by
toms have been inconsistent [21-25]. A systematic review Goldaroo Drug Company in Iran [31]. The placebo
[26] conducted on six randomized controlled trials (RCTs) tablets were produced in the School of Pharmacy of
with a total of 1163 peri- and post-menopausal women Tabriz University of Medical Sciences. These tablets
concluded that the efficacy of Black cohosh in reducing were the same as the Black cohosh tablets in shape,
the symptoms was currently not supported by fully con- color, and size, and were thus indistinguishable from
clusive evidence, and that further investigations were de- the Black cohosh tablets.
sirable. Another review [27] of 16 studies that addressed
the weaknesses of previous studies and their heterogeneity Setting and participants
found insufficient evidence to support the efficacy of Black Women who met the following criteria were eligible for
cohosh on early menopausal symptoms. recruitment: (1) age of 45–60 years; (2) no menstrual
Black cohosh is well tolerated and is generally safe cycle in the last 12 months; and (3) GCS score of 15–42.
[15,26,28,29]. However, some insignificant side effects, The exclusion criteria included: (1) high blood pressure
such as nausea, vomiting, headaches, and dizziness were (more than 140/90 mmHg); (2) history of breast cancer,
reported [15,26]. We found no data for toxic doses of uterine cancer, abnormal vaginal bleeding, liver disease,
Black cohosh. No serious side-event was reported even depression, hypertension, or hyperthyroidism; (3) use of
in a study [24] using a higher dose of Black cohosh that steroids or herbal medications for treatment of menopausal
included 128 mg/day standardized to 7.27 mg of triter- symptoms or psychiatric drugs within the last 2 months;
pene glycosides (ethanolic extract of Black cohosh). (4) sensitivity to spices or essences; (5) smoking; and
The Greene climacteric scale (GCS), which is used to (6) alcohol consumption.
assess the symptoms of menopause, is a comprehensive The subjects were selected from women referred to
validated tool consisting of 21 questions that women use two public health care centers affiliated to Beheshti Uni-
to rate how much they are bothered by the symptoms [30]. versity of Medical Sciences, Tehran, Iran. These centers
The inconclusive evidence on the efficacy of Black co- had the highest numbers of clients for family planning
hosh has resulted in inconsistent practices by clinicians services among the centers affiliated to the university.
regarding the prescription of Black cohosh in the study All participants had household records at the centers for
area, leading to confusion for some patients on their de- receipt of primary health care, including family planning
cision about its use. To provide more evidence in this services, in previous years and had reached the age of
area, this study aims to evaluate the efficacy of Black co- menopause. To contact the participants, we found their
hosh on early menopausal symptoms using an RCT. phone numbers from the records. Some of the eligibility
criteria were checked over the phone. The potentially
Methods eligible subjects were invited to attend the centers. At
Design the centers, the women were further informed about the
This study was a randomized, double-blind, placebo- study, the eligibility criteria were checked precisely, and
controlled trial. A total of 84 menopausal women were informed consent forms were signed by the eligible women.
randomly allocated into treatment and control groups The research protocol were approved (Code 9061) by
based on a block randomization with block sizes of 4 the Ethics Committee of Tabriz University of Medical
and 6 and an allocation ratio of 1:1. The allocation se- Sciences and registered at the Iranian Registry of Clinical
quence was identified by computerized random numbers. Trials with IRCT201107186709N4 on 15 January 2012
Sequentially numbered sealed envelopes of the same shape (http://www.irct.ir/searchresult.php?id=6709&number=4).
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Table 1 Demographic characteristics of the study participants in the treatment (Black cohosh) and control
(placebo) groups
Variables Treatment Control Statistical results
(n = 42) (n = 42)
Mean ± SD Mean ± SD
Age (years) 51.4 ± 4 51.7 ± 4.2 t = 0.78, df = 82, P = 0.43
Length of menopause (months) 35.1 ± 20.6 31.4 ± 21.3 t = 0.82, df = 82, P = 0.41
Systolic blood pressure (mmHg) 115.7 ± 13.5 115.2 ± 8.6 t = 0.19, df = 82, P = 0.84
Diastolic blood pressure (mmHg) 79.2 ± 6.7 77.3 ± 6.6 t = 1.30, df = 82, P = 0.19
Body mass index (kg/m2) 27.6 ± 3.6 26.3 ± 2.9 t = 1.83, df = 82, P = 0.07
n (%) n (%)
Education
Elementary 9 (21) 6 (14) χ2 = 4.49
Secondary 4 (9) 11 (26) df = 3
High school 20 (47) 19 (45) P = 0.21
Academic 9 (21) 6 (14)
Employment
Housewife 33 (78) 33 (78) χ2 = 0.22
Employed 4 (9) 5 (11) df = 2
Retired 5 (11) 4 (9) P = 0.89
Income adequacy
Yes 15 (35) 14 (33) χ2 = 0.17
To some extent 24 (57) 24 (57) df = 2
No 3 (7) 4 (9) P = 0.91
Exercise
Never 7 (17) 10 (24) χ2 = 0.71
Sometimes 15 (36) 13 (31) df = 3
Often 13 (31) 12 (28) P = 0.87
Always 7 (17) 7 (17)
Marital status
Married 40 (95) 36 (86) χ2 = 3.54
Single 1 (2) 2 (4) df = 3
Divorced 1 (2) 1 (2) P = 0.31
Widowed 0 (0) 3 (3)

The sample size was calculated using STATA software were the GCS subscale scores (vasomotor, physical, psy-
version 9.2 (Statasoft Inc., USA) based on a study by chiatric, and sexual symptoms) at the follow-ups as well as
Hakimi et al. [32]. Considering 28.1 as the mean and also possible side effects.
1.98 as the standard deviation for the GCS score in the
control group, a reduction in the GCS total score of at Data collection
least 15% by the treatment, a one-sided significance level Data were collected at baseline prior to the treatment,
of 0.05, a power of 0.80, and a 10% probable drop in the and also at weeks 4 and 8 after commencement of the
sample, the required sample size was calculated to be 42 treatment using a questionnaire. The questionnaire in-
participants per group. cluded demographic and GCS statements [30], which were
completed in face-to-face interviews by the participants at
Outcomes the visits. The participants were also given a form, and
The primary outcome was the GCS total score assessed were requested to mark their taking of the pills and the
at weeks 4 and 8 of follow-up and the secondary outcomes occurrence of any side effects (e.g., headaches, dizziness,
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Table 2 Comparisons of the treatment (Black cohosh) and control (placebo) groups in terms of the Greene climacteric
scale total and subscale scores at baseline and two follow-up time-points
Outcome variables Treatment Control Comparison of the groups
(n = 42) Mean ± SD (n = 42) Mean ± SD
Adjusted MD (95% CI) P Partial Eta2
Total score (0–63)
Baseline 33.8 ± 6.4 31.1 ± 6.3 2.7 (−0.1 to 5.4) 0.059
4 weeks 16.7 ± 7.7 22.9 ± 9.2 −7.8 (−11.1 to −4.4) < 0.001 0.21
8 weeks 8.0 ± 5.5 19.5 ± 11.0 −12.9 (−16.2 to −9.3) < 0.001 0.39
Vasomotor symptoms (0–6)
Baseline 4.0 ± 1.7 3.5 ± 1.6 0.5 (−2.9 to 1.2) 0.22
4 weeks 1.8 ± 2.0 2.6 ± 1.7 −1.1 (−0.4 to −1.8) 0.002 0.11
8 weeks 0.7 ± 1.6 2.4 ± 1.8 −1.9 (−1.2 to −2.6) < 0.001 0.26
Psychiatric symptoms (0–33)
Baseline 18.8 ± 4.8 18.8 ± 4.3 0.1 (−2.1 to 1.9) 0.92
4 weeks 10.8 ± 5.0 13.3 ± 6.4 −2.6 (−0.3 to −4.9) < 0.001 0.16
8 weeks 4.2 ± 3.5 11.4 ± 7.4 −7.3 (−9.6 to −5.0) < 0.001 0.31
Physical symptoms (0–21)
Baseline 7.7 ± 3.5 6.6 ± 2.7 1.1 (−0.3 to 2,5) 0.10
4 weeks 3.1 ± 2.3 4.7 ± 2.8 −2.0 (−3.1 to −1.0) < 0.001 0.06
8 weeks 1.4 ± 1.5 3.7 ± 2.4 −2.5 (−3.3 to −1.7) < 0.001 0.33
Loss of interest in sex (0–3)
Baseline 2.6 ± 0.8 2.4 ± 1.4 0.2 (−0.7 to 0.3) 0.47
4 weeks 1.8 ± 1.0 1.9 ± 1.0 −0.37 (−0.72 to −0.03) 0.03 0.06
8 weeks 1.6 ± 1.1 1.9 ± 1.0 −0.52 (−0.89 to −0.15) 0.006 0.09

nausea, and vomiting) on the form every day and return using SPSS for Windows 13.0 (SPSS Inc., USA). Values of
it to the researcher at the next visit. Furthermore, we P < 0.05 were considered to indicate statistical significance.
checked the treatment compliance and possible side
effects over the phone once a week. Results
The GCS scale consisted of 21 statements. Eleven state- There was no loss to follow-up and all participants con-
ments pertained to psychiatric symptoms, and included tinued the study to the end. Both groups were similar in
two parts, anxiety and depression. Seven statements terms of the personal and societal characteristics (Table 1).
assessed physical aspects and two assessed vasomotor The average age in both groups was approximately
symptoms. The final statement considered sexual desire 51 years. The majority of patients in both groups had
disorder. The severity of the symptoms was scored as high school education or above, and were married
zero (no symptoms), one (mild), two (moderate), and three housewives. Overall, 17% of women in the treatment
(severe) based on self-reporting [30]. To determine the group and 24% in the control group did no exercise at all.
reliability, a test-retest was used (r = 0.96). At baseline, the mean ± standard deviation of the GCS
total score was 33.8 ± 6.4 in the treatment group and
Statistical analysis 31.1 ± 6.4 in the control group, with no significant dif-
The normality of the quantitative variables for each of the ference. In addition, the groups had similar scores for
groups was confirmed using the Kolmogorov-Smirnov all GCS subscales (Table 2).
test. An independent t-test was used for comparison of The GCS total score in the treatment group was sig-
the baseline scores, and a general linear model with nificantly lower than that in the control group at both
repeated measures was used for comparison of the follow- week 4 [adjusted mean difference: −7.8 (95% confidence
up scores adjusted for the baseline values, time, and inter- interval: −11.1 to −4.4), P < 0.001] and week 8 [−12.9
action between time and group. The Greenhouse-Geisser (−16.2 to −9.3), P < 0.001]. The treatment group also
test was used to determine the interaction effect. A partial showed significantly more improvement than the control
Eta2 value was recorded for the effect size of the treatment group in all GCS subscale scores (vasomotor, psychiatric,
and the interaction. All data analyses were carried out physical, and sexual symptoms).
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Total

P<0.001* P=0.001 P=0.199

ES= 0.253* ES= 0.123 ES= 0.020

Black cohosh
Placebo

P<0.001 P=0.237
ES= 0.336 ES= 0.017

Figure 1 Trend in the Greene climacteric scale total score and subscale scores at the two follow-up time points (*results of the
Greenhouse-Geisser test in the general linear model with repeated measures for the interaction between time and group; ES: effect
size based on the partial Eta2).

At weeks 4 and 8, there were 51% and 77% reductions (P = 0.199 and P = 0.237, respectively) (Figure 1). No
in the GCS total score (relative effect) in the treatment side effects were reported in either of the groups.
group compared with 27% and 38% in the control group,
respectively. Reductions in the vasomotor symptom Discussion
score of 61% and 86% were observed in the treatment Intake of Black cohosh (6.5 mg of dried extract of the
group compared with 27% and 29% in the control group. roots of the plant) for 8 weeks, comprising one tablet
The reductions in the psychiatric symptom score were every night after dinner, reduced the symptoms in early
46% and 79% in the treatment group compared with post-menopausal women compared with intake of placebo.
31% and 42% in the control group. The reductions in The treatment efficacy increased with longer use.
the physical symptom score were 63% and 82% in the The results of this study are consistent with the results
treatment group compared with 27% and 42% in the of some previous studies comparing the effects of daily
control group. The reduction in the loss of interest in intake of 6.5 mg of dried rhizome extract of Black cohosh
sex score were 29% and 36% in the treatment group [21] or 40 mg of herbal drug Black cohosh with peri- and
compared with 8% and 10% in the control group. The post-menopausal women [22,23] on reducing climacteric
effect size was considerable (partial Eta2: > 0.3) in terms complaints compared with intake of placebo, and the
of the total, physical, and psychiatric symptoms at 8 weeks women in the early climacteric phase benefited more
of follow-up (Table 2). than those in the late phase [22].
The differences between the treatment and control The effects of Black cohosh on reducing climacteric
groups at week 8 were significantly higher than those at symptoms in peri- and post-menopausal women were
week 4 in terms of the total score (P < 0.001) and vaso- similar to those of other effective treatment methods like
motor (P = 0.001) and psychiatric (P < 0.001) subscale conjugated estrogens [23] and tibolone [33], and even
scores. In the other two subscales, physical and sexual higher than those of fluoxetine [34].
symptoms, the effects were higher at week 8, but the The present results appear inconsistent with the results
differences were not significant compared with week 4 of some other studies. Geller et al. [24] showed that the
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effect of Black cohosh (64 mg/day) in reducing the Acknowledgments

number of vasomotor symptoms was not significantly This article is extracted from an MSc thesis in midwifery and its research
project was approved by the Tabriz University of Medical Sciences with No.
different from that of placebo and was significantly lower 5/55/7304 dated 07 February 2012. We thank all the participants in this
than 0.625 mg of conjugated equine estrogens plus 2.5 mg research. We also wish to thank the people in charge of the Nursing and
medroxyprogesterone acetate. The difference may be Midwifery College and the Research Deputy of Tabriz University of Medical
Sciences for financial assistance, the people in charge of Sardar Jangal and
related to the longer interval between the initiation of Shahid Ghaffari Health and Treatment Centers and the Research Deputy of
treatment and the outcome assessment, since the study Shahid Beheshti University of Medical Sciences, and all other colleagues who
outcome was assessed at 12 months after initiation of helped us in conducting this research.

the treatment compared with 2 months in our study. Received: 11 May 2013 Accepted: 23 October 2013
Jacobson et al. [35] demonstrated that Black cohosh Published: 1 November 2013
was not significantly effective in reducing most post-
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doi:10.1186/1749-8546-8-20
Cite this article as: Mohammad-Alizadeh-Charandabi et al.: Efficacy of
black cohosh (Cimicifuga racemosa L.) in treating early symptoms of
menopause: a randomized clinical trial. Chinese Medicine 2013 8:20.

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