Table 2: Clinical studies between 2000 and 2012 on the efficacy of Cimicifuga racemosa in neurovegetative and psychic climacteric complaints, differentiated by extract and regulatory status (registered medicinal product-not registered as medicinal product).

Extract DER; extractant/standardization; brand name; manufacturer Regulatory statusFirst author, year of publicationDesignNumber of patientsDose (Cimicifuga-drug/day or control/day); duration of applicationMain resultsImpact on evidence

Isopropanolic special extract (iCR) DER 6–11 : 1; 40% Isopropanol Remifemin; Schaper & Brümmer, GermanyMedicinal product (EU and outside EU) Liske, 2002 RCT76: standard dose
76: high dose



39 mg
127 mg
3 months ( )
up to 6 months
( )

Significant improvement of the KMI; responder rate (KMI < 15) after 3 months approx. 70%; high dose during menopausal transition significantly superior; no influence on hormones and vaginal cytology
Osmers, 2005 RCT153: iCR
151: placebo
40 mg
3 months
Significant improvement of the MRS-total score versus placebo; strongest effect in vasomotor complaints (hot flushes, sweatings, and sleep disorders) and higher superiority during menopausal transition
Nappi, 2005 RCT32: iCR
32: HT (TTSE2)


40 mg
25  g + Progesterone
3 months
In both groups comparably strong, significant improvement of vasomotor complaints, anxiety, and depression; no influence of iCR on hormones, liver function, and endometrium
Bai, 2007 RCT122: iCR
122: tibolone

40 mg
2.5 mg
3 months
Comparably strong, significant reduction of the KMI in both groups; with better safety of iCR: superiority of iCR in the benefit-risk ratio
Schmidt, 2005 ONC50240 mg
3 months
Significant improvement of the modif. KMI, most pronounced reduction of hot flushes and sweatings
Vermes, 2005 ONC2,01640 mg
3 months
Significant improvement of the KMI, strongest for hot flushes, sweatings, sleeping difficulties, and anxiety
Julia Molla, 2009 ONC12240 mg
3 months
Significant increase in quality of life (Cervantes-HR-QoL-Scale), especially in the domains menopause/health and psyche

Isopropanolic special extract (iCR) (see previously) with Hypericum perforatum extract; standardized to 1 mg triterpene glycosides and 0.25 mg total hypericin Remifemin plus; Schaper & Brümmer, Germany Medicinal product (EU) Uebelhack, 2006 RCT151: iCR + Hyp
150: placebo

120 mg (week 1–8)
60 mg (week 9–16)
4 months
Significant superiority versus placebo in the improvement of MRS- and HAMD-Scores
Briese, 2007 OC3,114: iCR + Hyp
3,027: iCR


60–120 mg
40 mg
6 months ( )
up to 12 months
( )
In both groups, significant improvement of the MRS-total score and -subscore Psyche; for psychic complaints iCR + Hyp is significantly more effective than iCR monotherapy

No data on extractant and DER Cimicifuga-extract with hypericum extract, standardized to 1 mg terpene glycosides and 0.25 mg hypericin Gyno-plus; Jin-Yang Pharm, Korea Medicinal product (Korea)Chung, 2007 RCT47: CR + Hyp
42: placebo
According to SPC
3 months
Significant superiority in the improvement of the KMI versus placebo; no influence on hormones and vaginal cytology; significant increase of HDL in the CR + Hyp-group

Ethanolic extract (CR BNO 1055) DER 5–10 : 1; 58% ethanol Klimadynon; Bionorica, GermanyMedicinal product (EU and outside EU) Wuttke, 2003 RCT20: CR
22: HT (CE)
20: placebo
40 mg
0.6 mg
3 months
CR: comparable improvement of the MRS score to CE and superiority versus placebo, however, not significant; CR without effects on the endometrium, positive influence on bone markers and vaginal cytology
Wuttke, 2006RCT-Reana-lysisSee Wuttke, 2003 See Wuttke, 2003 Exploratory reanalysis: significant superiority of CR versus placebo in regard to improvement of daily sweats, nightly waking, and MRS subscores major climacteric complaints, somatic complaints, and mental score
Rauš, 2006 ONC40040 mg
12 months
No influence on the endometrium; significant improvement of MRS II and MRS II 4-week weighted score of hot flushes

Ethanolic extract (Cr 99) 4.5–8.5 : 1; 60% Ethanol Cimicifuga Generic, Klimadynon Uno; Kolkmann, Bionorica, GermanyMedicinal product (EU)Frei-Kleiner, 2005 RCT83: CR
44: placebo
42 mg
3 months
Superiority versus placebo in KMI and weekly weighted score of hot flushes, which is significant in patients with baseline KMI > 20

Ethanolic extract No information on DER, 50% ethanol Remixin, Mikro-Gen, TurkeyMedicinal product (Turkey)Oktem, 2007 RCT60: CR
60: Fluoxetine
40 mg
20 mg
6 months
Significant improvement in modified KMI, Beck’s Depression Scale, and RAND-36 QoL in both groups; CR: significant superiority versus Fluoxetine in KMI and monthly scores for hot flushes and night sweats

Ethanolic extract (Ze 450) DER 4.5–8.5 : 1; 60% ethanol Cimifemin; Zeller, SwitzerlandMedicinal product (Switzerland)Kaiser, 2008 RCT60: standard dose
60: high dose
60: placebo
40 mg
80 mg
3 months
CR: significant superiority versus placebo in KMI
high dose: significant superiority versus standard dose in KMI

Ethanolic extract
No information on DER, 70% ethanol, 2.5% triterpene glycosides Pure World, USA
No medicinal product (USA)Newton, 2006 RCT80: CR
76: Multibotanical
79: Multibotanical + Soy
32: CEE + MPA
84: placebo
160 mg extract?
200 mg + 9 further
ingredients

0.625 mg + 2.5 mg
12 months
No significant differences between CR and placebo for vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale Score

Ethanolic extract 20 : 1; 75% ethanol, standardized to 3.64 mg triterpene glycosides University of Illinois/National Institutes of Health, USANo medicinal product, only study medication (USA)Geller, 2009 RCT22: CR
22: red clover
23: CEE/MPA
22: placebo
128 mg
120/378 mg
0.625/2.5 mg
12 months
No significant improvement of the frequency of vasomotor complaints by CR versus placebo

No information on extractant and DER CimiPure 2.5%, Pure World, Inc., USANo medicinal product, food supplement (USA)Ruhlen, 2007 ONC6180 mg extract?
3 months plus 3 months wash out
Significant improvement of the KMI by CR, increase after wash out; no effects in serum estrogen markers, pS2, or cellular morphology of NAF

CE: conjugated estrogens; CEE: conjugated equine estrogens; CR: Cimicifuga racemosa; DER: drug-extract ratio; HAMD: Hamilton Rating Scale for Depression; HR-QoL: Health-Related Quality of Life; HT: hormone therapy; Hyp: Hypericum perforatum; iCR: isopropanolic Cimicifuga racemosa special extract; KMI: Kupperman Menopause Index; MPA: medroxy progesterone acetate; MRS: Menopause Rating Scale; NAF: nipple aspirate fluid; OC: open controlled; ONC: open noncontrolled; RAND-36 QoL: RAND-36 measure of Health-Related Quality of Life; pS2: pS2 gene; RCT: randomised controlled trial; SPC: summary of product characteristics; TTSE2: transdermal estradiol.
Impact on Evidence for efficacy: : confirmatory evidence; : exploratory evidence; : no evidence.