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.
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.


METHODS
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]).


CONCLUSIONS
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 in Asian women.
Bai
Wenpei
W
The First Hospital of Peking University, Department of Gynecology, Beijing, China.
Henneicke-von Zepelin
Hans-Heinrich
HH
Wang
Shuyu
S
Zheng
Shurong
S
Liu
Jianli
J
Zhang
Zhonglan
Z
Geng
Li
L
Hu
Lina
L
Jiao
Chunfeng
C
Liske
Eckehard
E
D000328:Adult; D044466:Asian People; D002681:China; D031885:Cimicifuga; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D008593:Menopause / Q000187:drug effects* / Q000208:ethnology*; D008796:Metrorrhagia / Q000139:chemically induced; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D048789:Phytoestrogens / Q000008:administration & dosage / Q000009:adverse effects; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000008:administration & dosage; D018709:Statistics, Nonparametric
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D048789:Phytoestrogens; D010936:Plant Extracts; C027385:tibolone