Mehrpooya M, Rabiee S, Larki-Harchegani A, et al. A comparative study on the effect of "black cohosh" and "evening primrose oil" on menopausal hot flashes.J Educ Health Promot. 2018;7:36. Published 2018 Mar 1. doi:10.4103/jehp.jehp_81_17

Publication Date: "Received July 05, 2017. Accepted August 27, 2017."

Peer Reviewed: Yes.

Study Design: "Randomized, double-blind clinical trial."

Methodology: Randomly divided 80 postmenopausal women with hot flashes into two groups by blocked randomization; one group received black cohosh, the other received EPO for 8 weeks; severity and number of hot flashes and quality of life measured at pre-intervention, 1st, 4th, and 8th weeks.

Sample Size: "80 postmenopausal women."

Controls Used: "The participants were randomly divided into two groups by blocked randomization."

Dose Used: "Group A was given 40 mg of black cohosh twice a day and Group B received 500 mg EPO twice a day for 8 continuous weeks."

Statistical Significance Declared: "Average severity of hot flashes in both groups and number of hot flashes in black cohosh group in 8th week were significantly lower than 1st week (P < 0.001)" "Number of hot flashes in primrose oil group in 8th week showed no significant differences (P = 0.32)." "The number of hot flashes and quality of life score in black cohosh arm compared to EPO showed a significant decrease in the 8th week (P < 0.05)." "All MENQOL scores were significantly improved in two groups (P < 0.05), but the percentage of improvement in black cohosh arm was significantly superior to EPO group."

Adverse Events: "No side effects noted during the study." "No side effects noted during this study by participants; also, in other studies the CR is considered as a safe drug." "However, the most probable side effects are mild gastric symptoms, which tend to disappear after a while. Headaches, vomiting, and dizziness may occur by using high doses."

Conflict of Interest: "There are no conflicts of interest."

Friederichsen L, Nebel S, Zahner C, Bütikofer L, Stute P. Effect of CIMicifuga racemosa on metaBOLIC parameters in women with menopausal symptoms: a retrospective observational study (CIMBOLIC).Arch Gynecol Obstet. 2020;301(2):517-523. doi:10.1007/s00404-019-05366-8

Publication Date: Published online: 16 November 2019

Peer Reviewed: Yes

Study Design: Monocentric retrospective cohort study

Methodology: Women over 40 screened between 2009 and 2016, treated with MHT or CR, at least one follow-up; metabolic serum parameters, body weight, menopausal symptoms measured; linear mixed-effects regression models for analysis

Sample Size: 174 women were included in the final analysis (CR n = 32, MHT n = 142)

Controls Used: Coded health-related data of all patients above age 40 presenting for first-time consultation at the Menopause Centre

Dose Used: Ze 450 at 13 mg dry extract (n = 25; 78%; recommended dose 1 tablet daily)

Statistical Significance Declared: We did not find any evidence for a change in body weight and metabolic parameters. For Ze 450, we found some evidence for a change of the total score (− 1.82 [95% CI − 3.65, 0.02]; p = 0.05) and the urogenital subscore (− 0.79 [95% CI − 1.60, 0.02]; p = 0.05)

Adverse Events: The net benefit would outperform the rare potential, mostly short-term gastrointestinal, side effects

Conflict of Interest: None stated in the text provided

Xi S, Liske E, Wang S, et al. Effect of Isopropanolic Cimicifuga racemosa Extract on Uterine Fibroids in Comparison with Tibolone among Patients of a Recent Randomized, Double Blind, Parallel-Controlled Study in Chinese Women with Menopausal Symptoms.Evid Based Complement Alternat Med. 2014;2014:717686. doi:10.1155/2014/717686

Publication Date: First published: 02 March 2014

Peer Reviewed: Yes

Study Design: Randomized, double-blind, controlled study

Methodology: Enrolled 244 patients aged 40–60 years with menopausal symptoms; treated with iCR 40 mg/day or tibolone 2.5 mg/day for 3 months; analyzed fibroid size by transvaginal ultrasonography

Sample Size: 244 patients (iCR N = 122, tibolone N = 122); subset of 62 women with fibroids (iCR N = 34, tibolone N = 28)

Controls Used: Randomized, double-blind, parallel-controlled

Dose Used: iCR of 40 mg crude drug/day

Statistical Significance Declared: The median myoma volume decreased upon iCR by as much as −30% (P = 0.016) but increased upon tibolone by +4.7%. The percentage of volume change, mean diameter change and geometric mean diameter change of the iCR group compared to tibolone were statistically significant (P = 0.016, 0.021, 0.016 respectively).

Adverse Events: Short term treatment (3 months) is safe for women with fibroids and the volume of fibroids may even decrease during treatment.

Conflict of Interest: The authors have confirmed that they do not have any conflict of interests regarding the publication of the paper.

Fritz H, Seely D, McGowan J, et al. Black cohosh and breast cancer: a systematic review.Integr Cancer Ther. 2014;13(1):12-29. doi:10.1177/1534735413477191

Publication Date: First published online February 25, 2013

Peer Reviewed: Yes

Study Design: Systematic review

Methodology: Searched MEDLINE, Embase, Cochrane Library, AMED; included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, 5 observational studies

Sample Size: Of 450 records, 26 articles included

Controls Used: Placebo, tamoxifen, raloxifene, aromatase inhibitors

Dose Used: Remifemin 1 tab 2 × daily at 40 mg/d; 20 mg BC extract twice daily × 4 wk

Statistical Significance Declared: Adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82; adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89

Adverse Events: One breast cancer recurrence in a patient receiving both tamoxifen and black cohosh; one hysterectomy in a patient receiving both tamoxifen and black cohosh; one appendectomy in a patient receiving tamoxifen and placebo; 10 minor adverse events

Conflict of Interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article

Huyen CTT, Luyen BTT, Khan GJ, et al. Chemical Constituents from Cimicifuga dahuricaand Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.Molecules. 2018;23(5):1083. Published 2018 May 4. doi:10.3390/molecules23051083

Publication Date: Published: 4 May 2018

Peer Reviewed: Yes

Study Design: The study was designed to search for novel anti-cancer compounds from natural plants

Methodology: The 70% ethanolic extract from the rhizomes of Cimicifuga dahurica was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells; phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of new compounds

Sample Size: Five among the 17 isolated compounds

Controls Used: The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit

Dose Used: MCF-7 cells exposed to 30 µg/mL of C. dahurica extract or 10 µM of purified compounds (1-17)

Statistical Significance Declared: Significant anti-proliferative effects (p ≤ 0.05) for five compounds, most significant for compound 7

Adverse Events: No specific adverse events noted in the study; further studies on safety are desirable

Conflict of Interest: The authors declare no conflict of interest

Shahmohammadi A, Ramezanpour N, Mahdavi Siuki M, et al. The efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis.Post Reprod Health. 2019;25(3):131-141. doi:10.1177/2053369119841166

Publication Date: First published online October 20, 2019

Peer Reviewed: Yes

Study Design: Systematic review and meta-analysis

Methodology: Searched databases of MEDLINE, ISI Web of Science, Scopus, and Cochran central register of controlled trials from inception to August 2017; included 21 trials assessing the effect of herbal medicines on anxiety and depression symptoms in menopausal women

Sample Size: Twenty-one trials were included into systematic review

Controls Used: Placebo

Dose Used: Cimifugol tablet (6.5 mg of dried extract of Black cohosh root, representing 0.12–0.18 mg of 27-deoxyactein)

Statistical Significance Declared: The psychosocial score of GCS was decreased significantly in black cohosh group compared to the placebo after four weeks (p < 0.001) and eight weeks (p < 0.001)

Adverse Events: "There were no serious adverse serious adverse events reported in the use of botanical extracts and no significance difference in safety parameters, including hepatotoxicity for black cohosh over the 12-month duration of the study."

Conflict of Interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article

Mohammad-Alizadeh-Charandabi S, Shahnazi M, Nahaee J, Bayatipayan S. Efficacy of black cohosh (Cimicifuga racemosa L.) in treating early symptoms of menopause: a randomized clinical trial. Chin Med. 2013 Nov 1;8(1):20. doi: 10.1186/1749-8546-8-20.

Publication Date: Published: 01 November 2013

Peer Reviewed: Yes

Study Design: This study was a randomized, double-blind, placebo-controlled trial

Methodology: Conducted on 84 early post-menopausal participants with GCS scores of 15 to 42; participants randomly allocated into treatment (6.5 mg of dried extract of Black cohosh roots daily) and control (placebo) groups; participants took one tablet per day for 8 weeks; GCS scores recorded at baseline, 4 and 8 weeks; data analysis using a general linear model with repeated measures

Sample Size: 84 early post-menopausal participants

Controls Used: Placebo

Dose Used: 6.5 mg of dried extract of Black cohosh roots daily

Statistical Significance Declared: The GCS total score 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)] (P < 0.001)

Adverse Events: No side effects were reported in either of the groups; some insignificant side effects, such as nausea, vomiting, headaches, and dizziness were reported

Conflict of Interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article

Castelo-Branco C, Gambacciani M, Cano A, Minkin MJ, Rachoń D, Ruan X, Beer A-M, Schnitker J, Henneicke-von Zepelin H-H, Pickartz S. Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms – an update on the evidence. Climacteric. 2021;24(2):109-119. doi:10.1080/13697137.2020.1820477.

Publication Date: Published online: 06 Oct 2020

Peer Reviewed: Yes

Study Design: A systematic literature search

Methodology: Searched MEDLINE, EMBASE, EMBASE Alert, BIOSIS, and PubMed for clinical studies with iCR published from 1997 to January 2020; included 35 clinical studies and one meta-analysis

Sample Size: 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR)

Controls Used: Placebo, low-dose transdermal estradiol, tibolone

Dose Used: Higher dosages of iCR as monotherapy or in combination with St. John’s wort (Hypericum perforatum [HP])

Statistical Significance Declared: Standardized mean difference of −0.694 in favor of iCR (p < 0.0001); effect sizes of −1.020 for iCR monotherapy and −0.999 for iCR+HP combination

Adverse Events: Few minor adverse events, frequency comparable to placebo; no evidence of hepatotoxicity; no significant changes in body weight, heart rate, blood pressure, or electrocardiogram

Conflict of Interest: "Potential conflict of interest. A.-M. Beer, A. Cano, M. Gambacciani, M. J. Minkin, D. Rachoń, and J. Schnitker report no conflict of interest. C. Castelo-Branco and X. Ruan received fees from Schaper & Brümmer outside the submitted work for lecturing at and chairing, respectively, a congress symposium on iCR in 2019. H.-H. Henneicke-von Zepelin and S. Pickartz are employees of Schaper & Brümmer, the manufacturer of iCR. The authors alone are responsible for the content and writing of this article."

Shahnazi M, Nahaee J, Mohammad-Alizadeh-Charandabi S, Bayatipayan S. Effect of black cohosh (cimicifuga racemosa) on vasomotor symptoms in postmenopausal women: a randomized clinical trial.J Caring Sci. 2013;2(2):105-113. Published 2013 Jun 1. doi:10.5681/jcs.2013.013

Publication Date: Published: 1 Jun. 2013

Peer Reviewed: Yes

Study Design: This was a randomized, double-blind, placebo-controlled clinical trial

Methodology: Performed on 84 postmenopausal women; participants randomly divided into control and intervention groups; intervention group received one black cohosh tablet per day, control group received one placebo tablet per day for eight weeks; severity of vasomotor symptoms and number of hot flashes recorded during pre-intervention phase, and 4 and 8 weeks after the intervention; data analyzed using repeated measures ANOVA and ANCOVA tests

Sample Size: This study was performed on 84 postmenopausal women

Controls Used: Placebo

Dose Used: One black cohosh tablet per day (6.5 mg dried extract of cohosh root)

Statistical Significance Declared: "The GCS total score 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)] (P < 0.001)"

Adverse Events: No side effects were reported in either of the groups; some insignificant side effects, such as nausea, vomiting, headaches, and dizziness were reported

Conflict of Interest: The authors declare no conflict of interest in this study