Cimicifuga racemosa isopropanolic extract for menopausal symptoms: an observational prospective case–control study

Abstract Objective We aimed to investigate the effectiveness of isopropanolic extract of Cimicifuga Racemosa (iCR) on reducing menopausal symptoms. Materials and Methods A single-center observational prospective case–control study was performed to assess the improvement of menopausal symptoms in menopausal women undergone iCR administration (cases) or no treatment (controls). Menopausal symptoms were assessed through a modified version of the Menopause Rating Scale questionnaire (mMRS) at T0 (baseline), T1 (1-month follow-up), and T2 (3 months follow-up). Univariate comparisons between cases and controls were performed by using the unpaired T test for two-tailed P value with α = 0.05 significance level. Results A total of 163 women (83 cases and 80 controls) were enrolled in the study. The difference in menopausal symptoms between cases and controls from T0 to T2, and from T0 to T1, was found significant for all analyses. In particular, the difference in all menopausal symptoms was 20.56 ± 0.90 points (95%CI: 18.77–22.33, p < .001) from T0 to T2, and 10.69 ± 0.6 (95%CI: 9.49–11.88, p < .001) from T0 to T1. Conclusion iCR may be effective in reducing menopausal symptoms, both after 1 month and after 3 months of treatment. The improvement was higher in vasomotor symptoms, sleep problems, and irritability.

[1]  S. Cuschieri The STROBE guidelines , 2019, Saudi journal of anaesthesia.

[2]  X. Ruan,et al.  Benefit–risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John’s wort in breast cancer patients , 2019, Climacteric : the journal of the International Menopause Society.

[3]  R. Salari,et al.  A review of effective herbal medicines in controlling menopausal symptoms , 2017, Electronic physician.

[4]  C. Farquhar,et al.  Long-term hormone therapy for perimenopausal and postmenopausal women. , 2017, The Cochrane database of systematic reviews.

[5]  L. Qin,et al.  Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats. , 2016, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[6]  N. Panay,et al.  2016 IMS Recommendations on women’s midlife health and menopause hormone therapy , 2016, Climacteric : the journal of the International Menopause Society.

[7]  A. Jackowski,et al.  Poor-fit indexes of Kupperman index: a psychometric analysis based on item response theory , 2015, Menopause.

[8]  Amy T. Wang,et al.  Menopausal Symptoms: Comparative Effectiveness of Therapies , 2015 .

[9]  J. Drewe,et al.  A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients , 2015, SpringerPlus.

[10]  M. Gass,et al.  The North American Menopause Society recommendations for clinical care of midlife women. , 2014, Menopause.

[11]  H. Jarry,et al.  eview he non-estrogenic alternative for the treatment of climacteric complaints : Black ohosh ( Cimicifuga or Actaea racemosa ) , 2013 .

[12]  M. Recanatini,et al.  Phytoestrogens in Postmenopause: The State of the Art from a Chemical, Pharmacological and Regulatory Perspective , 2013, Current medicinal chemistry.

[13]  Julie Brown,et al.  Phytoestrogens for menopausal vasomotor symptoms. , 2013, The Cochrane database of systematic reviews.

[14]  H. Meden,et al.  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)” , 2013, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[15]  A. Beer,et al.  Differentiated Evaluation of Extract-Specific Evidence on Cimicifuga racemosa's Efficacy and Safety for Climacteric Complaints , 2013, Evidence-based complementary and alternative medicine : eCAM.

[16]  R. Lobo,et al.  Global Consensus Statement on menopausal hormone therapy. , 2013, Maturitas.

[17]  R. Lobo,et al.  Global Consensus Statement on Menopausal Hormone Therapy , 2013, Climacteric : the journal of the International Menopause Society.

[18]  M. Leach,et al.  Black cohosh (Cimicifuga spp.) for menopausal symptoms. , 2012, The Cochrane database of systematic reviews.

[19]  M. Xiaoyan,et al.  Effects of black cohosh and estrogen on the hypothalamic nuclei of ovariectomized rats at different temperatures. , 2012, Journal of ethnopharmacology.

[20]  J. Sorkin,et al.  Reproductive history and hot flashes in perimenopausal women. , 2012, Journal of women's health.

[21]  I. Jacobs,et al.  Prevalence, frequency and problem rating of hot flushes persist in older postmenopausal women: impact of age, body mass index, hysterectomy, hormone therapy use, lifestyle and mood in a cross‐sectional cohort study of 10 418 British women aged 54–65 , 2012, BJOG : an international journal of obstetrics and gynaecology.

[22]  N. K. Popova,et al.  On the role of brain 5-HT7 receptor in the mechanism of hypothermia: Comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor , 2011, Neuropharmacology.

[23]  R. Osmers,et al.  Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract , 2011, Menopause.

[24]  S. Crawford,et al.  Association of Menopausal Vasomotor Symptoms With Increased Bone Turnover During the Menopausal Transition , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  Barbara Bloom,et al.  Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. , 2009, National health statistics reports.

[26]  F. Pérez-López,et al.  Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women , 2009, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[27]  J. Bolton,et al.  In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent. , 2008, Journal of agricultural and food chemistry.

[28]  E. Kennelly,et al.  Extraction Methods Play a Critical Role in Chemical Profile and Biological Activities of Black Cohosh , 2008 .

[29]  E. Sauter,et al.  Black Cohosh: Insights into its Mechanism(s) of Action , 2008, Integrative medicine insights.

[30]  E. Liske,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. , 2007, Maturitas.

[31]  H. Henneicke-von Zepelin,et al.  Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study. , 2007, Maturitas.

[32]  C. Brucker,et al.  First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055 , 2006, Menopause.

[33]  Hui Yang,et al.  Polyphenolic constituents of Actaea racemosa. , 2006, Journal of natural products.

[34]  K. Wernecke,et al.  Black Cohosh and St. John’s Wort for Climacteric Complaints: A Randomized Trial , 2006, Obstetrics and gynecology.

[35]  D. Mostajo,et al.  Menopausal transition in Movima women, a Bolivian Native-American. , 2005, Maturitas.

[36]  M. Birkhäuser,et al.  Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial. , 2005, Maturitas.

[37]  C. Loprinzi,et al.  Treatment of hot flushes in breast and prostate cancer , 2005, Expert opinion on pharmacotherapy.

[38]  E. Liske,et al.  Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms , 2005, Obstetrics and gynecology.

[39]  N. Ács,et al.  The effects of remifemin® on subjective symptoms of menopause , 2005, Advances in therapy.

[40]  F. Facchinetti,et al.  Efficacy of Cimicifuga racemosa on climacteric complaints: A randomized study versus low-dose transdermal estradiol , 2005, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[41]  J. Quinn,et al.  Estrogen control of central neurotransmission: Effect on mood, mental state, and memory , 1996, Cellular and Molecular Neurobiology.

[42]  L. Dennerstein,et al.  Women’s sexual functioning, lifestyle, mid-age, and menopause in 12 European countries , 2004, Menopause.

[43]  P. Potthoff,et al.  International versions of the Menopause Rating Scale (MRS) , 2003, Health and quality of life outcomes.

[44]  J. Pezzuto,et al.  Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. , 2003, Journal of agricultural and food chemistry.

[45]  E. Ernst,et al.  Pharmacological effects of Cimicifuga racemosa. , 2003, Life sciences.

[46]  B. Spengler,et al.  In vitro effects of the Cimicifuga racemosa extract BNO 1055. , 2003, Maturitas.

[47]  D. Seidlová-Wuttke,et al.  The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. , 2003, Maturitas.

[48]  J. Sutcliffe,et al.  No hypothermic response to serotonin in 5-HT7 receptor knockout mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[49]  G. Bifulco,et al.  Effects of genistein on the endometrium: ultrasonographic evaluation , 2003, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[50]  E. Liske,et al.  Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. , 2002, Journal of women's health & gender-based medicine.

[51]  H. Berendsen,et al.  The role of serotonin in hot flushes. , 2000, Maturitas.

[52]  H. H. Berendsen,et al.  Treatment of hot flushes with mirtazapine: four case reports. , 2000, Maturitas.

[53]  J. Bolton,et al.  Role of quinones in toxicology. , 2000, Chemical research in toxicology.

[54]  F. Kronenberg Hot flashes: Phenomenology, quality of life, and search for treatment options , 1994, Experimental Gerontology.

[55]  A. Green,et al.  Menopausal symptoms in Australian women , 1993, The Medical journal of Australia.

[56]  Fredi Kronenberg,et al.  Hot Flashes: Epidemiology and Physiologya , 1990, Annals of the New York Academy of Sciences.

[57]  F Kronenberg,et al.  Hot flashes: epidemiology and physiology. , 1990, Annals of the New York Academy of Sciences.

[58]  Leon Speroff,et al.  Clinical gynecologic endocrinology and infertility , 1983 .

[59]  W. Geisendorf [Menopause and post-menopause]. , 1974, Therapeutische Umschau. Revue therapeutique.