12,600
Views
19
CrossRef citations to date
0
Altmetric
Reviews

Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms – an update on the evidence

ORCID Icon, , ORCID Icon, , , , , , & ORCID Icon show all
Pages 109-119 | Received 09 Jul 2020, Accepted 03 Sep 2020, Published online: 06 Oct 2020

References

  • Bair YA, Gold EB, Zhang G, et al. Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women's Health Across the Nation. Menopause 2008;15:32–43
  • Peng W, Adams J, Hickman L, Sibbritt DW. Longitudinal analysis of associations between women's consultations with complementary and alternative medicine practitioners/use of self-prescribed complementary and alternative medicine and menopause-related symptoms, 2007–2010. Menopause 2016;23:74–80
  • Peng W, Adams J, Hickman L, Sibbritt DW. Complementary/alternative and conventional medicine use amongst menopausal women: results from the Australian Longitudinal Study on Women's Health. Maturitas 2014;79:340–2
  • Buhling K, Daniels B, Studnitz F, Eulenburg C, Mueck A. The use of complementary and alternative medicine by women transitioning through menopause in Germany: results of a survey of women aged 45–60 years. Complement Ther Med 2014;22:94–8
  • Posadzki P, Lee MS, Moon TW, Choi TY, Park TY, Ernst E. Prevalence of complementary and alternative medicine (CAM) use by menopausal women: a systematic review of surveys. Maturitas 2013;75:34–43
  • Upton R. Black Cohosh Rhizome Actaea racemosa L. syn. Cimicifuga racemosa (L) Nutt Standards of analysis, quality control, and therapeutics American Herbal Pharmacopoeia and Therapeutic Compendium Santa Cruz. CA American Herbal Pharmacopoeia 2002;1–38
  • Henneicke-von Zepelin HH. 60 years of Cimicifuga racemosa medicinal products: clinical research milestones, current study findings and current developmnt. Wien Med Wochenschr 2017;167:147–13
  • von Studnitz FS, Eulenburg C, Mueck AO, Buhling KJ. The value of complementary and alternative medicine in the treatment of climacteric symptoms: results of a survey among German gynecologists. Complement Ther Med 2013;21:492–5
  • Jiang B, Kronenberg F, Nuntanakorn P, Qiu MH, Kennelly EJ. Evaluation of the botanical authenticity and phytochemical profile of black cohosh products by high-performance liquid chromatography with selected ion monitoring liquid chromatography-mass spectrometry. J Agric Food Chem 2006;54:3242–53
  • Edwards SE, Da Costa Rocha I, Williamson EM, Heinrich M, Phytopharmacy-An Evidence-Based Guide to Herbal Medicinal Products. Chichester: John Wiley & Sons; 2015
  • Community herbal monograph on Cimicifuga racemosa (L.) Nutt., rhizoma [Internet]. 2010. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2011/01/WC500100981.pdf
  • European Union herbal monograph on Cimicifuga racemosa (L.) Nutt., rhizoma. EMA/HMPC/48745/2017 [Internet]. 2018. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Herbal_monograph/2017/08/WC500233056.pdf
  • Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. The Cochrane Library 2012;1–92
  • Beer A-M, Osmers R, Schnitker J, Bai W, Mueck AO, Meden H. Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms – comments on major statements of the Cochrane Collaboration report 2012 "black cohosh (Cimicifuga spp.) for menopausal symptoms (review). Gynecol Endocrinol 2013;29:1022–5
  • Schulz V, Hänsel R, Rationale Phytotherapie: Ratgeber für die ärztliche Praxis: Springer-Verlag; 2013
  • Beer AM, Neff A. Differentiated evaluation of extract-specific evidence on Cimicifuga racemosa's efficacy and safety for climacteric complaints. Evid Based Complement Alternat Med 2013;2013:860602
  • Beer AM. Cimicifuga racemosa bei klimakterischen Beschwerden. Z Phytother 2015;36:10–17
  • Naser B, Schnitker J, Minkin MJ, de Arriba SG, Nolte KU, Osmers R. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause 2011;18:366–75
  • Stoll W. Phytotherapeutikum beeinflußt atrophisches Vaginalepithel: Doppelblindversuch Cimicifuga vs. Oestrogenpräparat. Therapeutikon 1987;1:23–31
  • Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739–45
  • Liske E, Hänggi W, Henneicke-von Zepelin H-H, Boblitz N, Wüstenberg P, Rahlfs VW. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med 2002;11:163–74
  • Osmers R, Friede M, Liske E, Schnitker J, Freudenstein J, Henneicke-von Zepelin HH. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol 2005;105:1074–83
  • Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 2005;20:30–5
  • Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247–55
  • Bai W, Henneicke-von Zepelin H-H, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas 2007;58:31–41
  • Li Y, Cui M, Gao S. Efficacy of remifemin for control of climacteric symptoms. Prog Obstet Gynecol 2011;20:462–5
  • Sun N-x, Jin Z-j, Jia X-f, Li W. Black cohosh improves vaginal atrophy in postmenopausal women. Academic Journal of Second Military Medical University 2012;32:339–41
  • Huang YX, Song L, Zhang X, Lun WW, Pan C, Huang YS. [Clinical study of combined treatment of remifemin and paroxetine for perimenopausal depression]. Zhonghua Yi Xue Za Zhi 2013;93:600–2
  • 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
  • Chen J, Gao H, Li Q, et al. Efficacy and safety of remifemin on peri-menopausal symptoms induced by post-operative GnRH-a therapy for endometriosis: a randomized study versus tibolone. Med Sci Monit 2014;20:1950–7
  • Jiang K, Jin Y, Huang L, et al. Black cohosh improves objective sleep in postmenopausal women with sleep disturbance. Climacteric 2015;18:559–67
  • Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment – results of a large-scale, controlled, observational study. Maturitas 2007;57:405–14
  • Garcia-Perez MA, Pineda B, Hermenegildo C, Tarin JJ, Cano A. Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line. Fertil Steril 2009;91:1347–50
  • Lundström E, Hirschberg AL, Soderqvist G. Digitized assessment of mammographic breast density – effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo. Maturitas 2011;70:361–4
  • Li W, Sun N-X, Chen X, Lang D-F, Jin Z-J. 早期子宫内膜癌患者术后应用黑升麻制剂治疗绝经相关症状 [Cimicifuga racemosa for treatment of menopausal symptoms in patients with early endometrial cancer after operation]. Acad J Second Mil Med Univ 2013;32:562–4
  • Henneicke-von Zepelin HH, Meden H, Kostev K, Schröder-Bernhardi D, Stammwitz U, Becher H. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther 2007;45:143–54
  • Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer 2007;120:1523–8
  • Obi N, Chang-Claude J, Berger J, et al. The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study. Cancer Epidemiol Biomarkers Prev 2009;18:2207–13
  • Liske E. Phytokombination lindert psychovegetative Leiden. [Phytocombination alleviates psychovegatative disorders]. TW Gynäkologie 1997;10:172–5
  • Nesselhut T, Liske E, ed. Pharmacological measures in postmenopausal women with an isopropanolic aqueous extract of Cimicifugae racemosae rhizoma. 10th Annual Meeting of the North American Menopause Society (NAMS); 1999: Menopause.
  • Pockaj BA, Loprinzi CL, Sloan JA, et al. Pilot evaluation of black cohosh for the treatment of hot flashes in women. Cancer Invest 2004;22:515–21
  • Schmidt M, Polasek W, Käufeler R. Efficacy and safety of black cohosh (Cimicifuga racemosa, Cimifemin®) in menopause discomfort: surveillance study in practical terms [Wirksamkeit und Sicherheit von Traubensilberkerze (Cimicifuga racemosa, Cimifemin®) bei Menopausebeschwerden: Therapiebeobachtung unter Praxisbedingungen]. J Für Menopause 2005;1:27–32
  • Vermes G, Banhidy F, Acs N. The effects of Remifemin(R) on subjective symptoms of menopause. Adv Therapy 2005;22:148–54
  • Hirschberg AL, Edlund M, Svane G, Azavedo E, Skoog L, Schoultz BV. An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women. Menopause 2007;14:89–96
  • Arriaza Peso E, del Carmen Arévalo Páez M, Ángeles Grandas Alonso M, Olleros Izard T. Eficacia de Cimicifuga racemosa para el tratamiento de la clínica vasomotora y psíquica en pacientes menopáusicas. [Efficacy of Cimicifuga racemosa in the treatment of vasomotor and psychic symptoms in menopausal patients]. Progresos de Obstetricia y Ginecología 2008;51:20–7
  • Reame NE, Lukacs JL, Padmanabhan V, Eyvazzadeh AD, Smith YR, Zubieta JK. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 2008;15:832–40
  • Molla J, Garcia-Sanchez Y, Romeu Sarri A, Perez-Lopez FR. Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women. Gynecol Endocrinol 2009;25:21–6
  • Wu X. 莉芙敏改善妇科恶性肿瘤患者术后绝经综合征的临床研究 [Remifemin improve gynecological malignant tumor postoperative patients of menopause syndrome for the clinical research]. Dalian Medical University: Master Degree Thesis; 2011
  • Rostock M, Fischer J, Mumm A, Stammwitz U, Saller R, Bartsch HH. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints – a prospective observational study. Gynecol Endocrinol 2011;27:844–8
  • Wang C, Huang Q, Liang CL, et al. Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer. J Ethnopharmacol 2019;238:111840
  • Hofstatter EW, Trant AA, Stavris K, et al. The effect of black cohosh on Ki67 levels in DCIS patients. JCO 2018;36:e13541–e13541
  • Chen J-y. 莉芙敏与利维爱治疗围绝经期综合征的临床疗效观察 [Comparison on the efficacy and safety of Remifemin and Livial in the treatment of perimenopausal symptoms]. Hainan Med J 2013;24:1454–7
  • Zhang Q, Zhuang Z, Chen T. 莉芙敏治疗围绝经期综合征的安全性和疗效研究 [The efficacy and safety of Remifemin in the treatment of perimenopausae syndrome]. Journal of Chengdu Medical College 2015;10:229–32
  • Henneicke-von Zepelin H-H, ed. High-dose isopropanolic Cimicifuga racemosa-extract for climacteric complaints in perimenopausal women. Human Reproduction, 12th World Congress; 2005; Venice
  • Huang X. 黑升麻根茎提取物缓解乳腺癌患者绝经症状的临床研究 [The clinical research of Black cohosh extract in breast cancer patients with climacteric complaints]. Nanjing University of Chinese Medicine: Master Degree Thesis; 2011
  • Sarri G, Pedder H, Dias S, Guo Y, Lumsden MA. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. BJOG 2017;124:1514–23
  • Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006;63:375–82
  • Minuzzi L, Frey BN, Soares CN. Depression during the menopausal transition: an update on epidemiology and biological treatments. FOC 2012;10:22–7
  • Lehmann-Willenbrock E, Riedel HH. Klinische und endokrinologische Untersuchungen zur Therapie ovarieller Ausfallerscheinungen nach Hysterektomie unter Belassung der Adnexe. Zent bl Gynäkol 1988;110:611–18
  • Ruan X, Mueck AO, Beer AM, Naser B, Pickartz S. Benefit-risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John's wort in breast cancer patients. Climacteric 2019;22:339–47
  • Hadji P. Improving compliance and persistence to adjuvant tamoxifen and aromatase inhibitor therapy. Crit Rev Oncol Hematol 2010;73:156–66
  • Fallowfield L. Acceptance of adjuvant therapy and quality of life issues. Breast 2005;14:612–16
  • Assessment report on Cimicifuga racemosa (L.) Nutt., rhizoma [Internet]. 2011. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/05/WC500106358.pdf
  • Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment. Phytomedicine 2009;16:72–84
  • Teschke R. Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review. Menopause 2010;17:426–40
  • Teschke R, Bahre R, Fuchs J, Wolff A. Black cohosh hepatotoxicity: quantitative causality evaluation in nine suspected cases. Menopause 2009;16:956–65
  • Teschke R, Schmidt-Taenzer W, Wolff A. Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: is the liver-unspecific Naranjo scale precise enough to ascertain causality? Pharmacoepidemiol Drug Saf 2011;20:567–82
  • Struck D, Tegtmeier M, Harnischfeger G. Flavones in extracts of Cimicifuga racemosa. Planta Med 1997;63:289
  • Kennelly EJ, Baggett S, Nuntanakorn P, et al. Analysis of thirteen populations of black cohosh for formononetin. Phytomedicine 2002;9:461–7
  • Beck V, Unterrieder E, Krenn L, Kubelka W, Jungbauer A. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol 2003;84:259–68
  • Nisslein T, Koetter U, Freudenstein J. In vitro binding of an isopropanolic extract of black cohosh to selected central nervous receptors. Maturitas 2006;54:S65
  • Burdette JE, Liu J, Chen SN, Fabricant DS, et al. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J Agric Food Chem 2003;51:5661–70
  • Rhyu MR, Lu J, Webster DE, Fabricant DS, Farnsworth NR, Wang ZJ. Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor. J Agric Food Chem 2006;54:9852–7
  • Hui Z, Xiaoyan M, Mukun Y, et al. Effects of black cohosh and estrogen on the hypothalamic nuclei of ovariectomized rats at different temperatures. J Ethnopharmacol 2012;142:769–75
  • Garcia de Arriba S, Henneicke v, Zepelin H-H, Dimpfel W, Nolte K. Cimicifuga extract modulates brain activity: electropharmacogram from various brain areas in freely moving rats (Tele-Stereo-EEG). Maturitas 2015;82:318
  • Menopause: diagnosis and management. NICE guideline (NG23). Version 1.5 [Internet]. 2015. //www.nice.org.uk/guidance/ng23 https://www.nice.org.uk/guidance/ng23/evidence/full-guideline-pdf-559549261
  • Bodinet C, Freudenstein J. Influence of Cimicifuga racemosa on the proliferation of estrogen receptor-positive human breast cancer cells. Breast Cancer Res Treat 2002;76:1–10
  • Bodinet C, Freudenstein J. Influence of marketed herbal menopause preparations on MCF-7 cell proliferation. Menopause 2004;11:281–9
  • Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res Treat 2004;84:151–60
  • Hostanska K, Nisslein T, Freudenstein J, Reichling J, Saller R. Inhibitory effect of an isopropanolic extract of black cohosh on the invasiveness of MDA-MB 231 human breast cancer cells. In Vivo 2007;21:349–55
  • Nesselhut T, Bodinet C, Schneider P, Freudenstein J. Use of extract of Cimicifuga racemosa. US Patent No. 6,267,994 B1 Jul. 31, 2001
  • Crone M, Hallman K, Lloyd V, et al. The antiestrogenic effects of black cohosh on BRCA1 and steroid receptors in breast cancer cells. Breast Cancer (Dove Med Press) 2019;11:99–110
  • Freudenstein J, Dasenbrock C, Nisslein T. Lack of promotion of estrogen-dependent mammary gland tumors in vivo by an isopropanolic Cimicifuga racemosa extract. Cancer Res 2002;62:3448–52
  • Nisslein T, Freudenstein J, ed. Prepubertal treatment with black cohosh attenuates pathogenicity in the DMBA rat model of mammary carcinoma. 10th world congress on the menopause; 2002 P06-08; Berlin: Climacteric
  • Nisslein T, Freudenstein J, ed. Synergistic effects of Black Cohosh and Tamoxifen in an animal model of mammary carcinoma. 6th European Congress on Menopause; 2003: Maturitas
  • Einbond LS, Su T, Wu HA, et al. The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways. Int J Cancer 2007;121:2073–83
  • Yue GG, Xie S, Lee JK, et al. New potential beneficial effects of actein, a triterpene glycoside isolated from Cimicifuga species, in breast cancer treatment. Sci Rep 2016;6:35263
  • Ji L, Zhong B, Jiang X, et al. Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways. Oncotarget 2017;8:112498–515
  • Paplomata E, ÓRegan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther Adv Med Oncol 2014;6:154–66
  • Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 2014;4:64
  • Moser C, Vickers SP, Brammer R, Cheetham SC, Drewe J. Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice. Phytomedicine 2014;21:1382–9
  • Li B, Takeda H, Tsuiji K, et al. The antidiabetic drug metformin inhibits uterine leiomyoma cell proliferation via an AMP-activated protein kinase signaling pathway. Gynecol Endocrinol 2013;29:97–0
  • Tadakawa M, Takeda T, Li B, Tsuiji K, Yaegashi N. The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1α signaling pathway in ELT-3 cells. Mol Cell Endocrinol 2015;399:1–8
  • Ciarmela P, Islam MS, Reis FM, et al. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update 2011;17:772–90
  • Viereck V, Grundker C, Friess SC, et al. Isopropanolic extract of black cohosh stimulates osteoprotegerin production by human osteoblasts. J Bone Miner Res 2005;20:2036–43
  • Stute P, Pickartz S. Zusatznutzen eines isopropanolischen Cimicifuga-racemosa-Extrakts (iCR): positive Beeinflussung von Knochenstoffwechsel und -qualität. Z Phytother 2015;36:18–22
  • Nisslein T, Freudenstein J. Effects of an isopropanolic extract of Cimicifuga racemosa on urinary crosslinks and other parameters of bone quality in an ovariectomized rat model of osteoporosis. J Bone Miner Metab 2003;21:370–6
  • Cui G, Leng H, Wang K, et al. Effects of remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis. PLoS One 2013;8:e82815
  • Qiu SX, Dan C, Ding L-S, et al. A triterpene glycoside from black cohosh that inhibits osteoclastogenesis by modulating RANKL and TNFalpha signaling pathways. Chem Biol 2007;14:860–9
  • Biglia N, Cagnacci A, Gambacciani M, Lello S, Maffei S, Nappi RE. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017;20:306–12
  • Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010;49:1603–16
  • Islam MS, Akhtar MM, Ciavattini A, et al. Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids? Mol Nutr Food Res 2014;58:1667–84
  • Gordon JL, Rubinow DR, Thurston RC, Paulson J, Schmidt PJ, Girdler SS. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause 2016;23:1189–98
  • Da Y, Niu K, Wang K, et al. A comparison of the effects of estrogen and Cimicifuga racemosa on the lacrimal gland and submandibular gland in ovariectomized rats. PLoS One 2015;10:e0121470
  • Yang CL, Or TC, Ho MH, Lau AS. Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis. Clin Rev Allergy Immunol 2013;44:284–300