Efficacy of black cohosh extracts for improving low estrogen status induced by postoperative GnRHa treatment in patients with endometriosis: a systematic review / 浙江大学学报·医学版

OBJECTIVE@#To evaluate the efficacy of black cohosh extracts (BCE) in improving the low estrogen status induced by postoperative gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis.@*METHODS@#Randomized clinical controlled trial about the improvement of low estrogen status caused by GnRHa with the treatment of BCE in patients with endometriosis after laparoscopic surgery were retrieved from Medline (Ovid), PubMed, Cochrane Library, CNKI, CBMdisc, Wanfang and VIP databases before January 2020, and meta-analysis of included studies was performed by Revman 5.3 software.@*RESULTS@#Seven randomized controlled trials involving 745 patients were included in this study. Meta-analysis results showed that the addition of BCE did not alter hormone levels of patients, including serum estradiol levels [ =1.24, 95% (-4.58, 7.08), >0.05] and luteinizing hormone levels [ =-0.02, 95% (-0.15, 0.11), >0.05]. BCE effectively improved the perimenopausal symptoms induced by low estrogen status:improving hectic fever and sweating [ =0.1, 95% (0.02, 0.47), < 0.01], reducing the occurrence of insomnia symptoms [ =0.23, 95% (0.13, 0.39), < 0.01], improving fatigue [ =0.09, 95% (0.04, 0.20), < 0.01], reducing the occurrence of vaginal dryness [ =0.04, 95% (0.01, 0.30), < 0.01]. BCE affected Kupperman's menopausal index (KMI) score 12 weeks after the surgery [ =-11.50, 95% (-20.09, -2.90), < 0.01] and KMI score 24 weeks after the surgery [ =-23.68, 95% (-39.66, -7.69), < 0.01].@*CONCLUSIONS@#The limited evidence so far indicates that BCE could efficiently improve perimenopausal symptoms cause by low estrogen status of the patients recieved GnRHa treatment after surgery for endometriosis, but does not alter hormone levels of patients.

Effect of apoptosis on G361 cells by Cimicifuga rhizoma extract / 대한구강보건학회지

OBJECTIVES: To investigate whether the cytotoxic effect of Cimicifuga rhizoma extract is associated with cell death in the human keratinocyte (HaCaT) and human melanoma cell lines (G361). METHODS: Apoptosis induced by Cimicifuga rhizoma extract was confirmed by water-soluble tetrazolium salts-1 (WST-1) assay, immunocytochemistry, and western blot. Additionally, the release of cytochrome c and apoptosis-inducing factor (AIF) was visualized by confocal laser scanning microscopy. RESULTS: The results showed that Cimicifuga rhizoma extract significantly reduced the viability of G361 cells with half-maximal inhibitory concentration (IC 50) of 200 µg/ml, and the apoptotic process was found to occur via the activation of caspase-3 and caspase-9 pathways. Besides, the release of cytochrome c and AIF was also detected. CONCLUSIONS: This study suggests that Cimicifuga rhizoma extract causes apoptosis of human melanoma cells through the intrinsic apoptotic pathway.

Cimicifuga heracleifolia is therapeutically similar to black cohosh in relieving menopausal symptoms: evidence from pharmacological and metabolomics studies / 中国天然药物

In the market of botanical dietary supplements, Cimicifuga heracleifolia (CH) has always been considered as an adulterated species of Cimicifuga racemosa (CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized (OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography (Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry (GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.

Overview of the Effect of Herbal Medicines and Isoflavones on the Treatment of Cognitive Function

OBJECTIVES: The current overview aimed to present the effect of herbal medicines on cognitive function among menopausal women. METHODS: Two separate authors performed systematic search of the 3 databases of (the MEDLINE Scopus and the Cochrane Central Register Trials) from inception to January 2018. Methodological quality of each study was assessed using the AMSTAR. RESULTS: According to 2 reviews, soy seems to be effective in enhancing summary cognitive function and visual memory. The effect of isoflavones on cognition was affected by treatment duration as six weeks of treatment improved some dimensions of cognitive parameters, including mental flexibility and planning, and longer treatment period (6 months) improved category digit span test, digit symbol test, and visual scanning test score. The effect of phytoestrogen on cognitive function of menopausal women might be altered age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen. Combination of Gingko with ginseng could not improve sustained attention, episode memory, category generation or frontal lobe function. Gingko biloba had no significant effect on planning, memory and sustained attention, except for its limited effect on mental flexibility in late menopause. In addition, other herbal medicines like black cohosh showed no effective beneficial. CONCLUSIONS: Phytoestrogen, soy and isoflavones might have a limited beneficial effect on some aspects of cognition. The phytoestrogens affecting cognition might be modified by age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen.

Chemicals from Cimicifuga dahurica and Their Inhibitory Effects on Pro-inflammatory Cytokine Production by LPS-stimulated Bone Marrow-derived Dendritic Cells

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

Actaea racemosa (Cimicífuga), en las alteraciones del ciclo reproductivo femenino. Representación teatral / Actaea racemosa (Cimicífuga), in the alterations of the female reproductive cycle. Theatrical representation

La planta Actaea racemosa, también conocida como Cimicífuga racemosa o simplemente Cimicífuga, ha sido ampliamente usada la medicina autóctona tradicional de varios grupos indígenas norteamericanos, y como fitofármaco para el tratamiento de las dolencias presentes en las diversas etapas del ciclo reproductivo femenino: menarquia, menstruación, embarazo, parto, puerperio y menopausia. Si bien es cierto que estas etapas hacen parte de un ciclo natural y por lo tanto deberían estar libres de síntomas, algunas mujeres experimentan molestias de diverso grado de intensidad que se traducen al lenguaje médico como síntomas que pueden resultar incapacitantes. Estos síntomas se pueden expresar en las dimensiones física, mental y emocional produciendo cuadros característicos que son susceptibles de tratamiento con medicamentos homeopáticos siendo Actaea racemosa uno de los más útiles. Sin embargo, la materia médica homeopática ofrece otros medicamentos que también son de utilidad para el tratamiento de estos síntomas, motivo por el cual sería conveniente contar con métodos pedagógicos complementarios que permitan su fácil recordación. El presente trabajo tiene como propósito enriquecer el material didáctico disponible para la enseñanza de la homeopatía tomando como sujeto de estudio el medicamento Actaea racemosa para lo cual se elaboró una obra teatral utilizando los síntomas característicos del medicamento cubiertos por menos de 15 medicamentos en el repertorio Radar 10.5. Para el desarrollo de este trabajo se efectuó una revisión no sistemática en textos de materia médica de eminentes homeópatas como Nash, Kent, Farrington, Lathoud, y Vijnovsky, sobre el medicamento Actaea racemosa, así como de la fundamentación teórica para el diseño de la obra teatral.

Photochemistry and pharmacology of 9, 19-cyclolanostane glycosides isolated from genus Cimicifuga / 中国天然药物

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9, 19-cyclolanostane triterpenoid glycosides, which often exhibit extensive pharmacological activities. 9, 19-Cyclolanostane triterpenoid glycosides are distributed widely in genus Cimicifuga rather than in other members of the Ranunculaceae family. So far, more than 140 cycloartane triterpene glycosides have been isolated from Cimicifuga spp.. The aim of this review was to summarize all 9, 19-cyclolanostane triterpenoid glycosides based on the available relevant scientific literatures from 2000 to 2014. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.

Ultrasonographic observation of the breast in early postmenopausal women during therapy with Cimicifuga foetida extract and sequential therapy with estrogen and progestin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women.</p><p><b>METHODS</b>This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment.</p><p><b>RESULTS</b>In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check.</p><p><b>CONCLUSIONS</b>In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.</p>

Cycloartenol triterpenoid saponins from Cimicifuga simplex (Ranunculaceae) and their biological effects / 中国天然药物

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.

Topical application of herbal formula for the treatment of ligature-induced periodontitis

PURPOSE: The aim of this study was to investigate the therapeutic effects of a herbal formula, PerioH-035, containing Angelica sinensis, steamed Rehmannia glutinosa, Angelica dahurica, Cimicifuga heracleifolia, and Zanthoxylum piperitum on the periodontal breakdown in a well-established ligature-induced periodontitis model in rats. METHODS: Sprague-Dawley rats were randomly assigned to 1 of 4 groups: NL (non-ligatured), L (ligatured), P1 (ligatured and treated with 1 mg/mL PerioH-035), P100 (ligatured and treated with 100 mg/mL PerioH-035). Periodontitis was induced by placing a ligature around the mandibular first molars. PerioH-035 was topically applied to both sides of the first molar for 2 weeks. The right side of the mandibles was retrieved for micro-computed tomography (CT) and methylene blue staining to analyze alveolar bone loss. The left side of the mandibles was histologically analyzed by TRAP and H&E staining. The MMP-9 mRNA level in gingival tissue was investigated by RT-PCR. RESULTS: Alveolar bone resorption was significantly reduced in the PerioH-035-treated groups. The number of dense multi-nucleated cells found to be TRAP-positive by staining in the ligatured rats was markedly decreased by PerioH-035 application. In addition, periodontal tissue destruction, especially cementum demineralization, was ameliorated in the P1 and P100 groups. Moreover, gingival tissue from the PerioH-035-treated group showed a decrease in the MMP-9 mRNA level, resulting in recovery of collagen degradation. CONCLUSIONS: These results suggest that PerioH-035 has therapeutic effects on periodontitis, and thus, PerioH-035 shows promise as a treatment for periodontitis. GRAPHICAL ABSTRACT:

Identification of cimicifugae rhizoma and its adulterants using ITS2 sequence / 中国中药杂志

In order to identify Cimicifugae Rhizoma from its adulterants and to ensure its safe use, the internal transcribed spacer 2 (ITS2) sequence of Cimicifugae Rhizoma and its adulterants were amplified and bidirectionally sequenced by DNA barcoding technology. Sequence assembly and consensus sequence generation were performed by the CodonCode Aligner V3.7.1. The genetic distances were computed by MEGA 5.0. Identification analyses were performed using neighbor-joining (NJ) methods. The length of ITS2 sequence of the three origin plants of Cimicifugae Rhizoma include Cimicifuga heracleifolia, C. foetida, C. dahurica was 217, 219 and 219 bp, respectively. Their intraspecific genetic distance was much lower than the interspecific genetic distance with their closely related species. The NJ tree of ITS2 indicated that the three origin plants of Cimicifugae Rhizoma formed a monophyletic clade, Cimicifugae Rhizoma and its adulterants could be distinguished clearly. The authors proposed that ITS2 sequence was suitable for the authentication of Cimicifugae Rhizoma and its adulterants.

Investigation of anodized titanium implants coated with triterpenoids extracted from black cohosh: an animal study

PURPOSE: The purpose of this study was to evaluate bone response to anodized titanium implants coated with the extract of black cohosh, Asarum Sieboldii, and pharbitis semen. MATERIALS AND METHODS: Forty anodized titanium implants were prepared as follows: group 1 was for control; group 2 were implants soaked in a solution containing triterpenoids extracted from black cohosh for 24 hours; group 3 were implants soaked in a solution containing extracts of black cohosh and Asarum Sieboldii for 24 hours; group 4 were implants soaked in a solution containing extracts of pharbitis semen for 24 hours. The implants from these groups were randomly and surgically implanted into the tibiae of ten rabbits. After 1, 2, and 4 weeks of healing, the nondecalcified ground sections were subjected to histological observation, and the percentage of bone-to-implant contact (BIC%) was calculated. RESULTS: All groups exhibited good bone healing with the bone tissue in direct contact with the surface of the implant. Group 2 (52.44 +/- 10.98, 25.54 +/- 5.56) showed a significantly greater BIC% compared to that of group 3 (45.34 +/- 5.00, 22.24 +/- 2.20) with respect to the four consecutive threads and total length, respectively. The BIC% of group 1 (25.22 +/- 6.00) was significantly greater than that of group 3 (22.24 +/- 2.20) only for total length. CONCLUSION: This study did not show any remarkable effects of the extract of black coshosh and the other natural products on osseointegration of anodized titanium implants as coating agents. Further studies about the application method of the natural products on to the surface of implants are required.

New 9, 19-cycloartane triterpenoid from the root of Cimicifuga foetida / 中国天然药物

AIM@#To study the 9, 19-cycloartane triterpenes from the roots of Cimicifuga foetida.@*METHOD@#Chromatographic separations by silica gel, C18 reversed phase silica gel, and high-performance liquid chromatography (HPLC) were used. All of the structures were elucidated on the basis of spectroscopic analysis and chemical methods.@*RESULTS@#Five 9, 19-cycloartane triterpenes, (3β, 12β, 15α, 24R)-12, 2'-diacetoxy-24, 25-epoxy-15-hydroxy-16, 23-dione-3-O-α-L-arabinopyranoside (1), actein (2), 23-epi-26-deoxyactein (3), asiaticoside B (4), and 12β-hydroxycimigenol (5) were isolated from the roots of Cimicifuga foetida.@*CONCLUSION@#Compound 1 is a new triterpene with two acetoxy groups at C-2' and C-12.

A new phenolic amide glycoside from Cimicifuga dahurica / 药学学报

A new phenolic amide glycoside, cimicifugamide A (1) along with four known compounds, trans-feruloyl tyramine 4-O-beta-D-glucopyranoside (2), (+)-isolariciresinol 3-O-beta-D-glucopyranoside (3), cimidahurine (4), and 24-epi-7, 8-didehydrocimigenol-3-O-beta-D-xylopyranoside (5) were isolated from the rhizomes of Cimicifuga dahurica. Compound 3 was identified as a lignan and has been obtained from Cimicifuga genus for the first time. The structure of compound 1 was elucidated by IR, UV, HR-MS and NMR spectroscopic methods.

Study on quality evaluation of cimicifugae rhizoma from different producing areas by HPLC fingerprint / 中国中药杂志

To establish a fingerprint for Cimicifugae Rhizoma from different producing areas. Column kromasil (4.6 mm x 250 mm, 5 microm) was employed with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution. The flow rate was 1.0 mL x min(-1), the detection wavelength was 254 nm. Twenty chromatographic peaks were extracted as the common peaks of fingerprint, and 21 batches of samples were compared and classified with such methods as similarity evaluation, cluster analysis and principle component analysis. The results showed 12 common peaks and three categories of samples. The method was so highly reproducible, simple and reliable that it could provide basis for quality control and evaluation of Cimicifugae Rhizoma from different producing areas.

Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is now recognized that Cimicifuga foetida extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. This paper compares the clinical effects of different regimens of three-month course on climacteric symptoms in Chinese women, so as to evaluate the efficacy and safety of Cimicifuga foetida extract.</p><p><b>METHODS</b>This was a prospective, randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into 3 groups to take different kinds of medicine for 3 months; participants were given Cimicifuga foetida extract daily in group A (n = 32), given estradiol valerate and progesterone capsule cycle sequentially in group B (n = 32), and given estradiol valerate and medroxyprogesterone acetate cycle sequentially in group C (n = 32). The questionnaires of Kupperman menopause index, Menopause-Specific Quality of Life, and Hospital Anxiety and Depression Scale were finished before and after the treatment. The status of vaginal bleeding and breast tenderness was recorded every day.</p><p><b>RESULTS</b>Eighty-nine participants (89/96, 92.7%) completed the treatment. Kupperman menopause index decreased after taking the medicine for 3 months in each group (with all P < 0.001), but the score after the treatment was higher in group A than in the other 2 groups. Except for the score of sexual domain in group A (P = 0.103), the scores of all domains of the Menopause-Specific Quality of Life decreased significantly after the treatment in all groups (with all P ≤ 0.01). Score of anxiety decreased significantly in group A (P = 0.015) and B (P = 0.003). Incidence of breast tenderness was 12.9% (4/31) in group A, 36.7% (11/30) in group B, and 14.3% (4/28) in group C. Incidence of vaginal bleeding was 6.5% (2/31) in group A, 26.7% (8/30) in group B, and 82.1% (23/28) in group C.</p><p><b>CONCLUSIONS</b>Cimicifuga foetida extract is effective and safe in the treatment of menopausal syndrome. It is worth extending its use in the treatment of climacteric complaints, especially among those having contradiction for hormone replacement therapy.</p>

Classification of Cimicifuga species based on 1H-NMR fingerprint combined with pattern recognition technique / 中国中药杂志

The metabolomic analysis of three Cimicifuga species was performed using H-NMR spectroscopy and pattern recognition (PR) techniques. A broad range of metabolites could be detected by 'H-NMR spectroscopy without any chromatographic separation. The analysis using principal component analysis (PCA) and discriminant partial least square (DPLS) of the 1H-NMR spectrum showed a clear discrimination between C. foetida and the other two species. The major metabolites responsible for the discrimination were triterpenoid saponins and saccharides. These results indicated that the combination of 1H-NMR and PR provides a useful tool for chemotaxonomic analysis and authentification of Cimicifuga species, and could used for the quality control of plant materials.

Effect of Korean Native Cimicifuga Species on Proliferation of Vascular Smooth Muscle Cells / 대한폐경학회지

OBJECTIVES: To examine the effect of extracts of Korean native Cimicifuge species on cell proliferation in vascular smooth muscle cells (VSMC). METHODS: VSMC were isolated from rat aorta. Cell proliferation was assessed by measure of bromodeoxyuridine incorporation into the cells. Differences in Reactive oxygen species (ROS) levels were examined after exposure to the extracts of Korean native Cimicifuge species using the detection reagents dichlorofluorecin diacetate. The rhizomes/roots were air-dried and milled with a commercial food mixer. Milled rhizomes/roots of each Cimicifuga species were separately extracted by 80% ethanol, absolute methanol, and 40% 2-propanol using homogenizer and evaporated under reduced pressure at low temperatures. Effects of extracts dissolved in phosphate-buffered saline (0.3 mg/mL) were examined. RESULTS: Ethanolic, methanolic or propanolic extracts of 4 Korean native Cimicifuge species (Cimicifuga [C] davurica, C. japonica, C. heracleifolia var. bifida Nakai, C. simplex) were screened. The addition of extracts of each Korean native Cimicifuge species to cells in the presence of 10% fetal bovine serum (FBS) potently inhibited cell proliferation. Significant decrease of 23%-30% was observed. Vitamin E, a potent antioxidant, inhibited 10% FBS-stimulated cell proliferation of VSMC. We also demonstrated that extracts of each Korean native Cimicifuge species decreased intracellular ROS generation induced with 10% FBS. The effect of Korean native Cimicifuge species was not species-specific and solvent-specific. CONCLUSION: TExtracts of Korean native Cimicifuge species inhibit VSMC proliferation via inhibition of intracellular ROS. These findings suggest that Cimicifuge species used for reducing menopause symptoms might be cardioprotective in women.

Effect of Black Cohosh on Genital Atrophy and Its Adverse Effect in Postmenopausal Women / 대한폐경학회지

OBJECTIVES: It is to evaluate the effect of black cohosh on genital atrophy and its adverse effect in postmenopausal women. METHODS: A total of 100 postmenopausal women having moderate to severe degree of climacteric symptoms were randomly allocated to receive black cohosh combined proparation (n = 50) or placebo (n = 50) daily for 12 weeks. A total of seventy eight subjects completed the study. The effect of black cohosh on vaginal atrophy was evaluated by measuring Maturation value (MV). MV was determined from vaginal smear at 0 and 12 weeks of treatment. Safety assessment included vital signs, physical examinations, adverse events, and routine laboratory parameters. Assessments were carried out at the beginning, and after 4, 8, and 12 weeks of treatment. RESULTS: The mean (+/- standard deviation) MV decreased 0.18 (0.48 +/- 0.33 to 0.30 +/- 0.24) in the black cohosh group and 0.13 (0.44 +/- 0.31 to 0.31 +/- 0.22) in the placebo group. There was no statistical difference between the groups. But adverse events were observed in 7 (14%) patients in the black cohosh group and 6 (12%) patients in the placebo group, without statistical significance. No significant effects were observed on blood pressure, heart rate, body temperature, physical findings, and laboratory values. Black cohosh was well tolerated. CONCLUSION: Black cohosh did not exert estrogenic effects with regards to vaginal atrophy. Further studies on the long-term safety and the appropriate doses of cohosh are needed.