Black Cohosh

OBJECTIVE: This randomized, double-blind, parallel-group clinical trial aimed to evaluate the efficacy of Black Cohosh, Soy Isoflavones, and SDG Lignans in alleviating menopausal symptoms compared to a placebo. METHODS: Ninety-six postmenopausal women aged 45-60 years were enrolled. Participants were randomized to receive either the study supplements or a placebo for 90 days, with Menopause Rating Scale (MRS) scores collected at baseline and every 4 weeks to monitor symptom changes. Secondary outcomes assessed included hormonal variations and the incidence of adverse symptoms. RESULTS: Of the initial cohort, 90 participants completed the study with high adherence. Significant improvements were observed in the treatment group across all MRS domains: somatic (- 54.3% difference, p < 0.01), psychological (- 54.3% difference, p < 0.01), urogenital (-37.3% difference, p < 0.01), and total score (- 48.0% difference, p < 0.01). Hormonal changes were modest yet statistically significant for FSH (- 6.7% difference, p < 0.01) and estradiol (12.6% difference, p < 0.01). Adverse events were minimal, transient, and did not require cessation of supplementation. CONCLUSION: Black Cohosh, Soy Isoflavones, and SDG Lignans significantly reduced menopausal symptoms with a favorable safety profile. These findings support the potential of this supplement combination as a therapeutic option for menopausal symptom management. TRIAL REGISTRATION: ClinicalTrials.gov NCT06328348. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Menopausal symptoms severely reduce the quality of life of post-menopausal women worldwide. Nutraceuticals are widely prescribed as a viable and safer alternative and complementary approach to standard therapies. The aim of this study was to evaluate the clinical efficacy and safety of a nutraceutical in post-menopausal women. METHODS: The study was designed as a randomized, double-blinded, placebo-controlled clinical trial. Post-menopausal women aged 45-60 years old were enrolled and randomly assigned to either treatment (n = 50) or placebo group (n = 51). The intervention, a proprietary combination of soy isoflavone, black cohosh, chasteberry and evening primrose oil extracts, and the placebo, were administered to each group for total of 12 weeks. Menopausal symptoms, endocrine profiles, and blood chemistry were evaluated at baseline, 6 weeks, and 12 weeks of the study. RESULTS: Nutraceutical supplementation demonstrated a statistically significant reduction in hot flushes and sweating (p < 0.0001), sleep problems (p < 0.0005), depressed mood (p = 0.0004) and irritability symptoms (p < 0.0003) compared with the placebo group. There were no significant differences in hormonal levels between the test and placebo groups, however levels of C-reactive protein were significantly decreased. Moreover, serum LDL-C and triglyceride levels were significantly lower than baseline levels in the treatment group at 6- and 12-week timepoints. No adverse effects were reported during the treatment. CONCLUSION: These data indicate that a nutraceutical containing a combination of four medicinal herbs effectively and safely improved menopausal symptoms, as well as general health indicators, in post-menopausal women.

BACKGROUND: Serotonin toxicity is a well-described phenomenon that is commonly attributed to a variety of drug-drug combinations. Some unregulated herbal supplements have been implicated in the onset of serotonin toxicity, however, there is currently minimal literature available on the potential for black cohosh to contribute to rhabdomyolysis and serotonin toxicity, in spite of its known serotonergic properties. CASE REPORT: A middle-aged woman presented to the emergency department with serotonin toxicity and rhabdomyolysis shortly after taking black cohosh supplements in the setting of long-term dual antidepressant use. The serotonin toxicity and rhabdomyolysis resolved with IV fluids, benzodiazepines, and discontinuation of the offending drugs. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients are sometimes not aware of how over-the-counter supplements might interact with their prescription medications. Female patients taking black cohosh to manage hot flashes and menopausal symptoms could be at risk for developing rhabdomyolysis and serotonin toxicity if they are also taking other serotonergic agents.

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care. © 2022. The Author(s).

Commercial formulations of 29 commonly used herbal supplements (HSs) and grapefruit juice were evaluated for drug interaction potential via quantification of their CYP3A inhibitory potential in two in vitro experimental models of human small intestine, cryopreserved human intestinal mucosa (CHIM), and cryopreserved human enterocytes (CHEs). Two CYP3A substrates were used-in the studies with CHIM, CYP3A activity was quantified via liquid chromatography tandem mass spectrometry quantification of midazolam 1'-hydroxylation, whereas in CHE, luciferin-IPA metabolism to luciferin was quantified by luminescence. Upon treatment of CHIM with the estimated lumen concentration of the HS upon each oral administration (manufacturers' recommended dosage dissolved in 200 ml of culture medium), >80% CYP3A inhibition was observed for green tea extract, St. John's wort, valerian root, horehound, and grapefruit juice. Less than 50% inhibition was observed for fenugreek, aloe vera, guarana, soy isoflavone, maca, echinacea, spirulina, evening primrose, milk thistle, cranberry, red yeast rice, rhodiola, ginkgo biloba, turmeric, curcumin, white kidney bean, garlic, cinnamon, saw palmetto berries, panax ginseng, black elderberry, wheat grass juice, flaxseed oil, black cohosh, and ginger root. The results were confirmed in a a dose-response study with HSs obtained from three suppliers for the four inhibitory HSs (green tea extract, horehound, St. John's wort, valerian root) and three representative noninhibitory HSs (black cohosh, black elderberry, echinacea). Similar results were obtained with the inhibitory HSs in CHE. The results illustrate that CHIM and CHE represent physiologically relevant in vitro experimental models for the evaluation of drug interaction potential of herbal supplements. Based on the results, green tea extract, horehound, St. John's wort, and valerian root may cause drug interactions with orally administered drugs that are CYP3A substrates, as was observed for grapefruit juice. SIGNIFICANCE STATEMENT: In vitro evaluation of 29 popular herbal supplements in cryopreserved human intestinal mucosa identified green tea extract, horehound, St. John's wort, and valerian

OBJECTIVE: Assessing adverse drug reactions (ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia (and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea (Echinacea purpurea), valerian (Valeriana officinalis), black cohosh (Actaea racemosa) and ginkgo (Ginkgo biloba). METHODS: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration (TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using GraphPad Prism software. RESULTS: Most ADRs were mild or moderate. However, every herbal medicine was associated with life-threatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs (30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity. CONCLUSION: This study highlights the lack of public awareness with regard to herb-drug interactions, since most of the severe ADRs involved a herb-drug interaction.

Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of black cohosh and actein on rat liver tissue, using Ingenuity and ToxFX analyses. Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) for 24 h or actein for 6 and 24 h, at 35.7 mg/kg, and liver tissue collected for gene expression analysis. Ingenuity analysis indicates the top canonical pathways are, for black cohosh, RAR Activation, and, for actein, Superpathway of Cholesterol Biosynthesis, at 24 h. Actein alters the expression of cholesterol biosynthetic genes, but does not inhibit HMG-CoA reductase activity. Black cohosh and actein inhibited the growth of human breast and colon cancer cells and synergized with the statin simvastatin. Combinations of black cohosh with certain classes of statins could enhance their activity, as well as toxic, such as inflammatory liver, side effects. Transcriptomic analysis indicates black cohosh and actein warrant further study to prevent and treat cancer and lipid disorders. This study lays the basis for an approach to characterize the mode of action and toxicity of herbal medicines.

BACKGROUND: Herbal products have grown steadily across the globe and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic Herb-drug Interactions (HDIs) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human Carboxylesterases 1 (CES1) and 2 (CES2) metabolize endogenous and exogenous chemicals including many important therapeutic medications. The growing number of CES substrate drugs also underscores the importance of the enzymes. Herein, we summarized those potential inhibitors and inducers coming from herbal constituents toward CES1 and CES2. We also reviewed the reported HDI studies focusing on herbal products and therapeutic agents metabolized by CES1 or CES2. METHODS: We searched in PubMed for manuscript published in English after Jan 1, 2000 combining terms "carboxylesterase 1", "carboxylesterase 2", "inhibitor", "inducer", "herb-drug interaction", "inhibitory", and "herbal supplement". We also searched specific websites including FDA and EMA. The data of screened papers were analyzed and summarized. RESULTS: The results showed that more than 50 natural inhibitors of CES1 or CES2, including phenolic chemicals, triterpenoids, and tanshinones were found from herbs, whereas only few inducers of CES1 and CES2 were reported. Systemic exposure to some commonly used drugs including oseltamivir, irinotecan, and clopidogrel were changed when they were co-administered with herb products such as goldenseal, black cohosh, ginger, St. John's Wort, curcumin, and some Chinese compound formula in animals. CONCLUSION: Nonclinical and clinical studies on HDIs are warranted in the future to provide safety information toward better clinical outcomes for the combination of herbal products and conventional drugs.

Nearly 25% of U.S. adults report concurrently taking a prescription medication with a dietary supplement. Some supplements, such as St. John's wort and goldenseal, are known to cause clinically important drug interactions and should be avoided by most patients receiving any pharmacologic therapy. However, many other supplements are predicted to cause interactions based only on in vitro studies that have not been confirmed or have been refuted in human clinical trials. Some supplements may cause interactions with a few medications but are likely to be safe with other medications (e.g., curcumin, echinacea, garlic, Asian ginseng, green tea extract, kava kava). Some supplements have a low likelihood of drug interactions and, with certain caveats, can safely be taken with most medications (e.g., black cohosh, cranberry, ginkgo, milk thistle, American ginseng, saw palmetto, valerian). Clinicians should consult reliable dietary supplement resources, or clinical pharmacists or pharmacologists, to help assess the safety of specific herbal supplement-drug combinations. Because most patients do not disclose supplement use to clinicians, the most important strategy for detecting herb-drug interactions is to develop a trusting relationship that encourages patients to discuss their dietary supplement use.

Herbal medicines have been widely used for thousands of years, and now are gaining continued popularity worldwide as a complementary or alternative treatment for a variety of diseases, rehabilitation and health care. Since herbal medicines contain more than one pharmacologically active ingredient and are commonly used with many prescribed drugs, there are potential herb-drug interactions. A variety of reported herb-drug interactions are of pharmacokinetic origin, arising from the effects of herbal medicines on metabolic enzymes and/or transporters. Such an alteration in metabolism or transport can result in changes in absorption, distribution, metabolism, and excretion (e.g., induction or inhibition of metabolic enzymes, and modulation of uptake and efflux transporters), leading to changed pharmacokinetics of the concomitantly prescribed drugs. Pharmacokinetic herb-drug interactions have more clinical significance as pharmacokinetic parameters such as the area under the plasma concentration-time curve (AUC), the maximum plasma concentration (Cmax) or the elimination half-life (t1/2) of the concomitant drug alter. This review summarizes the mechanism underlying herb-drug interactions and the approaches to identify the interactions, and discusses pharmacokinetic interactions of eight widely used herbal medicines (Ginkgo biloba, ginseng, garlic, black cohosh, Echinacea, milk thistle, kava, and St. John's wort) with conventional drugs, using various in vitro, animal in vivo, and clinical studies. The increasing understanding of pharmacokinetic herb-drug interactions will make health care professionals and patients pay more attention to the potential interactions.

Herbal products are commonly used to treat clinical conditions and are often purchased online without the supervision of a healthcare provider. The use of herbals remains controversial because of widespread exaggerated claims of clinical efficacy and safety. We conducted an online search of 13 common herbals (including black cohosh, echinacea, garlic, ginkgo, ginseng, green tea, kava, saw palmetto, and St John's wort) and reviewed the top 50 Web sites for each using a Google search. We analyzed clinical claims, warnings, and other safety information. A total of 1179 Web sites were examined. Less than 8% of retail sites provided information regarding potential adverse effects, drug interactions, and other safety information; only 10.5% recommended consultation with a healthcare professional. Less than 3% cited scientific literature to accompany their claims. Key safety information is still lacking from many online sources of herbal information. Certain nonretail site types may be more reliable, but physicians and other healthcare professionals should be aware of the variable quality of these sites to help patients make more informed decisions. Published by Elsevier Inc.

OBJECTIVES: The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan. METHODS: Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements. KEY FINDINGS: The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway. CONCLUSIONS: Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial. © 2013 Royal Pharmaceutical Society.

OBJECTIVES: To evaluate the effectiveness of black cohosh extract 40 mg/day for relieving moderate to severe menopausal symptoms and improving quality of life in Thai women. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in a menopause clinic of a tertiary-care university hospital during 2011-2013. Participants were peri- or postmenopausal Thai women aged at least 40 years, who have moderate to severe menopausal symptoms evaluated using the Kupperman index (KI). Outcome measures included KI, frequency of hot flushes, Menopause-Specific Quality of Life (MENQOL) score, participants' global satisfaction and safety outcomes. RESULTS: There were 54 participants assigned to treatment (black cohosh extract 40 mg/day, n = 27) or placebo group (n = 27). Both the treatment and placebo groups had comparable baseline KI scores (33.9 ± 7.9 vs. 31.3 ± 6.8), frequency of hot flushes (3.1 ± 2.0 vs. 2.8 ± 2.1), and MENQOL scores, all of which improved with time. Neither the improvements nor the global satisfaction were significantly different between the two groups; but the proportion of participants with moderate to severe symptoms seemed to be lower in the treatment group than in the placebo group (40% vs. 60%, p = 0.174). There was no serious adverse event or significant change in liver function tests. CONCLUSIONS: A black cohosh extract of 40 mg/day is not superior to a placebo for relieving moderate to severe menopausal symptoms or improving quality-of-life scores in Thai women.

In postmenopausal women estrogens in combination with progestins have beneficial effects on climacteric complaints and on osteoporosis but this hormone replacement therapy (HRT) bears the risk of increased mammary carcinomas and cardiovascular diseases. Phytoestrogens at low doses have little or no effects on climacteric complaints, at high doses they mimic the effects of estrogens. Therefore other plant derived substances are currently intensively investigated. Extracts of the rhizome of black cohosh (Cimicifuga racemosa=CR) did not bind to estrogen receptors and were shown to be devoid of estrogenic effects on mammary cancer cells in vitro and on mammary gland and uterine histology in ovariectomized rats. In addition in this rat model the special extract CR BNO 1055 inhibited the occurrence of hot flushes and development of osteoporosis. In postmenopausal women CR BNO 1055 reduced major climacteric complaints as effectively as conjugated estrogens and significantly more than placebo. Similar data were published for other European CR preparations whereas 2 US American preparations were ineffective. This was most likely due to the too high doses or due to the adulteration with Asian Cimicifuga preparations. In all European studies neither effects in the uterus nor in mammary glands were observed. The effective compounds in CR are most likely neurotransmitter-mimetic in nature: dopaminergic, noradrenergic, serotoninergic and GABAergic effects were demonstrated and some have been structurally identified. We conclude that CR extracts at low doses are effective to ameliorate climacteric complaints but are devoid of adverse estrogenic effects. These finding strengthens the role of CR extracts as substitutes for HRT. This article is part of a special issue entitled: Special Issue on Phytoestrogens.

OBJECTIVE: To investigate the efficacy-safety balance of the isopropanolic extract of Actaea (=Cimicifuga) racemosa (iCR, Remifemin) in comparison with tibolone in Chinese women with climacteric complaints. METHOD: The randomized, double-blind, controlled 3-month study in 5 centers of 3 cities in China enrolled 244 menopausal patients aged 40-60 years and with a Kupperman Menopause Index (KMI)>or=15. The participants were assigned to either iCR corresponding to 40 mg crude drug/day (N=122) or tibolone 2.5mg/day (N=122) orally. The primary endpoint was the combination of the Mann-Whitney values (MWV) of the KMI and the frequency of adverse events (benefit-risk balance) at end of treatment (MWV>0.5 shows superiority; MWV>0.36 shows non-inferiority). RESULTS: KMI decreased from 24.7+/-6.1 to 11.2+/-6.2 and 7.7+/-5.8 (iCR) and to 11.2+/-7.2 and 7.5+/-6.8 (tibolone) at 4 and 12 weeks. This remarkable and clinically relevant improvement was similar in both treatment groups (MWV=0.47; 95% CI=0.39-0.54; p(non-inferiority)=0.002) showing statistical significant non-inferiority of iCR to tibolone. The KMI-responder rate was similar in both groups (84% and 85%). The safety evaluation showed for both groups a good safety and tolerability profile, however, there is a significant lower incidence of adverse events (p<0.0001) in favor of the herbal treatment. None of the postmenopausal iCR patients experienced vaginal bleeding in contrast to tibolone (17 cases). Breast and abdominal pain as well as leukorrhea was mostly observed in the tibolone group (p=0.015, p=0.008, p=0.002). No serious adverse event was observed in the iCR-group, however, two occurred in the tibolone-group. The benefit-risk balance for iCR was significantly (p=0.01) superior to tibolone (MWV=0.56; 95% confidence interval [0.51-0.62]). CONCLUSION: The efficacy of iCR (medicinal product Remifemin) is as good as tibolone for the treatment of climacteric complaints, even for moderate to severe symptoms, whereby iCR is clearly superior regarding the safety profile. This iCR containing medicinal product is an excellent option for treatment of climacteric complaints which has now for the first time been verified i

OBJECTIVE: Menopausal hormone therapy is standard treatment, but some women use complementary therapies. This review examines complementary therapies for menopause to inform International Menopause Society (IMS) recommendations. METHOD: A systematic search of six databases (January 2022-December 2024) identified randomized controlled trials (RCTs) and systematic reviews on complementary therapies for menopause. Outcomes included menopausal, vasomotor, genitourinary, cardiometabolic, sleep symptoms, bone health and safety. The study quality and certainty of evidence were evaluated using Cochrane Risk of Bias (RoB2), A MeaSurement Tool to Assess Systematic Reviews (AMSTAR 2) and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: From 3187 citations, 158 studies were included: one overview, 36 meta-analyses, seven systematic reviews and 114 RCTs. While promising evidence was found for acupuncture, Chinese herbal medicine (CHM), herbs, nutrients, mind-body/touch therapies for a variety of symptoms, most was of low/very low certainty. High-certainty evidence supports vitamin D safety; and moderate-certainty evidence supports black cohosh (vasomotor/menopausal symptoms), CHM (menopausal symptoms, sleep, blood pressure), acupuncture + CHM (sleep) and vitamin D (fracture risk). Most complementary therapies are safe. CONCLUSION: Vitamin D, black cohosh, CHM and acupuncture + CHM may improve some menopausal symptoms, but overall evidence remains limited. More rigorous research is needed on the efficacy and safety of complementary therapies for menopause. Plain Language Summary: Menopausal hormone therapy is the main treatment for menopause symptoms, but many women also use complementary therapies alongside conventional care. This review summarizes the available research on different complementary therapies used by women during and after menopause.Six databases were searched and 158 studies included, such as clinical trials, systematic reviews and meta-analyses on complementary therapies used by menopausal women. Overall, the quality of these trials and reviews was low.Many complementary therapies showed promising results, such as acupun

IMPORTANCE: Black cohosh (BC) is a herbal medicine being prescribed for the management of climacteric complaints. This is the first review to assess the quality of evidence for BC as measured by adherence to Consolidated Standards of Reporting Trials (CONSORT) extensions for herbal interventions and harms. OBJECTIVE: Herbal medicines such as Actaea racemosa ( A. racemosa ; synonym Cimicifuga racemosa , BC) are commonly being used by women seeking relief from menopausal (climacteric) complaints. Our objective is to evaluate the quality of reporting of clinical trials investigating A. racemosa for climacteric complaints, by grading their adherence to both the CONSORT extensions for herbal interventions, and for reporting adverse events (harms). EVIDENCE REVIEW: A systematic search of the databases: AMED, CINAHL, EBSCO, Academic Search Ultimate, Google Scholar, PubMed and Science Direct, was conducted in April 2023 and another search done March 2024. The search phrase employed included relevant herbal or herbal product keywords ["black cohosh," "actaea racemosa," "cimicifuga racemosa," "BNO 1055," "remifemin," "Ze 450"] combined using the Boolean operator term AND with keywords regarding climacteric complaints ["menopausal symptoms," "menopause," "climacteric complaints"]. Additional citation searching was conducted to identify any other published studies. Articles were included if they were clinical trials of oral use of A. racemosa in humans. Quality assessment of included articles was undertaken to review adherence to the CONSORT Statement Extensions for reporting on herbal interventions, and harms (adverse events). FINDINGS: Fourteen records were included in the final analysis. Adherence to the herbal extension for the CONSORT ranged between 39% and 87%, with four of them receiving an adherence rating of 50% or less. Adherence to the Harms Extension for the CONSORT ranged between 6% and 90%, with three of the articles receiving an adherence rating of 50% or less. CONCLUSIONS AND RELEVANCE: This is the first time a systematic review of the quality of clinical trial reports of BC, using the CONSORT herbal extension and harms checklists, has been conducted. The wi

ETHNOPHARMACOLOGICAL USES: Black cohosh, also known as Cimicifuga sp., is one of the most widely used ethnomedicine for the treatment of major health issues in women. Some reports show that Cimicifuga sp. exhibit anti-cancer, anti-viral, anti-microbial, anti-pyretic, and anti-inflammatory properties. PURPOSE OF THIS REVIEW: The objective of this comprehensive review is to furnish current and exhaustive knowledge pertaining to the pharmacological, phytochemical, and therapeutic properties of Cimicifuga sp. MATERIALS AND METHODS: In this review, all the available information was collected on Cimicifugasp. via computerized search using Google Scholar, PubMed, Research Gate, Sci-Hub, supplementary resources (books, government reports, and Ph.D. theses). RESULT: The phytochemical investigation on Cimicifuga sp. has shown phytoconstituents such as triterpenoid glycosides, phenylpropanoid, flavonoids, saponin, lignan, nitrogenous compounds, alkaloids, 4α-Methyl steroids and some other component like monoterpene lactones cimicifugolides A-C etc. Cimicifuga conveys a wide scope of research on in-vitro and in-vivo pharmacological potential, like anti-cancer, anti-microbial, anti-viral, anti-inflammatory, estrogenic, anti-oxidant, anti-neoplastic, anti-depressant, anti-Alzheimer, and anti-climacteric properties. CONCLUSION: This article discusses the medicinal and traditional histories of various Cimicifuga species. Because quality control and safety assessments of Cimicifuga species are currently lacking, only a limited portion of the plant may be used as medication. The majority of current research focuses on triterpene glycosides. Although there are a variety of additional molecules that may have novel biological functions, systematic investigations of these compounds are lacking. The Cimicifuga plant has to go through a lot of studies before it can be completely used in clinics as a viable medicinal contender.

Weight gain is a frequent problem in perimenopausal and postmenopausal women. Cimicifuga racemosa (CR) is a popular treatment option for menopausal symptoms. The aim of this review was to investigate whether there is scientific evidence that CR causes weight gain. We searched our database for medically confirmed, spontaneous adverse events regarding weight gain, literature for case reports and randomized controlled trials. Thirty cases in total were spontaneously reported in 15 years. The causality was not considered certain/likely in any of the cases. A nurse (consumer) assessed the causality as possible. Only one case was published in the literature. However, no change in body fat composition was reported, and the causality seems unlikely. Of the 31 identified studies, 17 were double-blind placebo-controlled, five were double-blind reference-controlled and nine were open reference-controlled. In total, 1839 women were treated with CR for up to 12 months. Two studies reported weight gain as an adverse event; however, no significant differences in weight changes were observed between the groups. One case of weight gain (about 2 kg) was reported, but the authors did not specify in which treatment group. In conclusion, this study provides no scientific evidence that the use of Cimicifuga racemosa causes weight gain in menopausal women.

OBJECTIVE: Menopause symptoms affect the various dimensions of women's lives and they can lead to reduction of their quality of life. Phytoestrogens can be used as an approach to diminish these symptoms. The aim of this systematic review was to investigate the effect of phytoestrogens on the treatment of urogenital menopause symptoms. STUDY DESIGN: PubMed, EMBASE, Web of Science, Cochrane library,Scopus and ProQuest were systematically searched from 2000-2020. All randomized clinical trials were included. The quality of the selected papers was evaluated by the CONSORT checklist. RESULTS: 33 eligible high-quality papers were reviewed. Various forms of phytoestrogens such as Pueraria Mirifica, fennel, Hop plant(Humuluslupulus L.), Glycine Max (L.) Merr, soy, red clover, black cohosh, ginsing, cimicifugaracemosa, genistein, diadzein, glycitein and isoflavone in the form of oral capsules and pill, food supplement, enriched powder, vaginal gel, cream and suppository could improve menopausal urogenital symptoms. The recovery rate in vaginal use of these phytoestrogens was greater than other consumptions. CONCLUSIONS: After using a variety of phytoestrogens in different forms indicators of urogenital atrophy and urinary disorders improved and women's sexual function improved after treatment. The use of phytoestrogens as a safe, low-risk compared to hormone therapy and almost accessible method for women can relieve urogenital symptoms and promote the sexual satisfaction and quality of life.

Polycystic ovary syndrome (PCOS) is a common cause of female infertility. To conduct a systematic review assessing the efficacy and safety of black cohosh for ovulation-induction through hormone regulation and increased endometrial thickness to improve pregnancy rates in women with PCOS-related infertility. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used. A search of Medline, Embase, International Pharmaceutical Abstracts, Science Direct, and Cumulative Index of Nursing and Allied Health Literature spanning origin to December 19, 2020 was conducted using keywords and permutations of "black cohosh" and "PCOS." A search for "PCOS" in the National Clinical Trials database and International Clinical Trials Registry Platform was conducted in December 2020 to identify additional records. Eligibility criteria included reported efficacy or safety outcomes; studies in women with PCOS; English language; and primary literature. Eligible records were evaluated using applicable risk-of-bias tools. A total of 181 records were screened after deduplication from 207 results. Two randomized controlled trials (RCT) met inclusion criteria. Review of 1386 records from clinical trial registries and subsequent scoping searches resulted in identification of 4 additional records (3 published). Improvement in hormone regulation and endometrial thickness were found for black cohosh groups compared to clomiphene citrate (CC). Three RCTs reported improved pregnancy rates using black cohosh plus CC. There were no differences in adverse events. Studies demonstrated several risk-of-bias concerns. There is a lack of high-quality evidence supporting the effectiveness of black cohosh for improving pregnancy rates in PCOS-related infertility. Short-term use of black cohosh appears to be safe.

INTRODUCTION: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. OBJECTIVE: To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. METHODS: A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. RESULTS: Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. CONCLUSION: For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.

A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR (p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort (Hypericum perforatum [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

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 [ MD=1.24, 95% CI(-4.58, 7.08), P&gt;0.05] and luteinizing hormone levels [ MD=-0.02, 95% CI(-0.15, 0.11), P&gt;0.05]. BCE effectively improved the perimenopausal symptoms induced by low estrogen status:improving hectic fever and sweating [ OR=0.1, 95% CI(0.02, 0.47), P &lt; 0.01], reducing the occurrence of insomnia symptoms [ OR=0.23, 95% CI(0.13, 0.39), P &lt; 0.01], improving fatigue [ OR=0.09, 95% CI(0.04, 0.20), P &lt; 0.01], reducing the occurrence of vaginal dryness [ OR=0.04, 95% CI(0.01, 0.30), P &lt; 0.01]. BCE affected Kupperman's menopausal index (KMI) score 12 weeks after the surgery [ MD=-11.50, 95% CI(-20.09, -2.90), P &lt; 0.01] and KMI score 24 weeks after the surgery [ MD=-23.68, 95% CI(-39.66, -7.69), P &lt; 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. 目的: 系统评价黑升麻提取物改善子宫内膜异位症患者术后促性腺激素释放激素激动剂（GnRHa）治疗导致低雌激素状态的有效性。 方法: 计算机检索至2020年1月，在Medline、PubMed、Cochrane Library、中国期刊全文数据库（CNKI）、中国生物医学文献数据库、万方数据和维普中国科技期刊数据库中，检索子宫内膜异位症患者腹腔镜手术后GnRHa疗程中加入黑升麻提取物辅助治疗以缓解GnRHa造成的低雌激素状态的临床随机对照试验，对符合纳入标准的文献进行质量评价，使用Revman 5.3软件对数据进行meta分析。 结果: 最终纳入7篇随机对照研究，总计745例患者。meta分析结果显示，与对照组比较，黑升麻提取物的加入不会影响患者体内激素水平，包括血清雌二醇水平（ MD=1.24，95% CI：-4.58~7.08，

Endocrine therapy in breast cancer survivors can cause severe 'climacteric' symptoms, which may compromise therapy adherence. To determine whether such symptoms can be treated with herbal medication containing black cohosh in the form of isopropanolic Cimicifuga racemosa extract (iCR) alone or in fixed combination with St John's wort (Hypericum perforatum [HP]) (iCR + HP), a systematic literature search was conducted. Results were viewed in relation to experimental data and metabolism of endocrine therapies. Most breast cancer survivors receiving endocrine therapy experienced reductions in climacteric symptoms under iCR/iCR + HP. Tamoxifen's interference potential may be countered by using higher iCR doses or iCR + HP. No estrogen-like effects at the breast or on hormones were seen. After breast cancer, even if receiving tamoxifen, patients using iCR/iCR + HP had significantly increased recurrence-free survival rates compared to non-users. These results are substantiated by experimental data demonstrating antiproliferative and anti-invasive effects of iCR in breast cancer cells and enhancement of the antineoplastic effects of tamoxifen. There are no known clinical interactions for iCR and HP with endocrine therapies. The HP extract used in iCR + HP did not exhibit any clinically relevant interaction potential. In conclusion, with its positive benefit-risk profile, iCR/iCR + HP may offer a safe non-hormonal therapeutic option for breast cancer survivors receiving endocrine therapy.