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Hananja Brice-Ytsma (MNIMH, MSc, DipED, DipTh)Module Leader, Link TutorArchway Clinic of Herbal MedicineArchway CampusHighgate HillLondon N19 5LWhttp://creativecommons.org/licenses/by-nc-nd/2.0/uk/Is Cimicifuga racemosa a viable alternative to HRTStudies on Cimicifuga racemosa have been done since 1950, in the last 5 yearstrials have been done under stricter guidelines and have found CR to be effectivein reducing menopausal symptoms, especially in perimenopausal women, with moresevere symptoms. CR looks promising on the effect on the bone metabolism and couldpossibly play a role in preventing osteoporosis, more research needs to be done toindicate the effectiveness. CR has been found to be helpful in menopausal symptomsin breastcancer patients where estrogen cannot be given and research indicatesthat CR has possibly added benefits in its antiproliferative action on cancergrowth, on estrogen dependent tumours as well as on non-estrogen dependenttumours. The adverse effects on stimulating uterine growth are not present with CRin the maximum length of trial done for one year, and have not been seen in theanimal trials. With the amount of evidence available the question needs to beasked why Cimicifuga racemosa is not prescribed regularly. Cimicifuga is easy toget hold of in the health food shops, and many women will self prescribe.Hananja Brice-YtsmaJuly 2005Is Cimicifuga racemosa (CR) a viable alternative to HRTIntroduction;HRT has been used to relieve menopausal symptoms and to prevent disease such asosteoporosis and dementia, cardiovascular disease. The women’s Health Initiative (WHI) study was a large clinical trial ofpostmenopausal women (age range 50-79) designed to see whether estrogen with orwithout progestins could prevent chronic conditions such as heart disease anddementia. The estrogen with progestins portion of the trial ended early because ofincreased incidence of breast cancer. A link was shown between HRT and increasesin blood clots, stroke and heart diseases (Writing Group for the Women’s HealthInitiative Investigators. 2002). Women in the WHI were mostly older (mean age 62)than those who typically seek HT for vasomotor symptoms (mean age 52). None of thestudy participants had severe menopausal symptoms. Benefits were documented suchas a decrease in the risk of hip fracture, colorectal cancer. The women whocontinued in estrogen only did not show an increase in breast cancer.Ultimately the question needs to be addressed if the risks (Writing Group for theWomen’s Health Inititative Investigators 2002) outweigh the benefits, only aftermany years, there are studies that provide data which reversed the perception thatHRT works to prevent diseases such as coronary heart disease and dementia.Many women now try to avoid HRT and are looking for alternatives (Kang et al2002). The availability and use of alternatives to HRT hasa british study involving about a million women taking HRTprovided information onlong term use (Rossouw et al 2002). Findings suggested that a variety of estrogen–progestin combination therapies, estrogen and tibolone, increased risks to womento develop breast cancer. The data suggests that all preparations analysed,irrespective of the type of the estrogen and the progestins compound or the modeof administrations bear risks. An increase in fatality of breast cancers was alsofound (Beral V 2003). Comparison of HRT with placebo in older women with coronaryheart disease revealed increased rates of venous thromboembolism and biliary tractsurgery without favourable trends in overall rates of cardiovascular diseases(Hulley et al 2000)Ultimately the question needs to be addressed if the risks (Writing Group for theWomen’s Health Inititative Investigators 2002) outweigh the benefits, only aftermany years, there are studies that provide data which reversed the perception thatHRT works to prevent diseases such as coronary heart disease and dementia.Many women now try to avoid HRT and are looking for alternatives (Kang et al2002). The availability and use of alternatives to HRT has grown significantly(Newton et al 2002). Cimicifuga racemosa is the most used form as an alternativeto HRT (Newton et al 2002).Cimicifuga racemosa trials;In 1997, over ten million monthly units of Cimicifuga racemosa extract were soldin Germany, the United States and Australia (Keenan et al 2003) The efficacy and safety of Cimicifuga racemosa has been under scrutiny since 1950where in Germany it became commonly prescribed by gynaecologists for menopausalsymptoms. By 1962 there are 14 clinical studies reported involving 1500 patients,financed by the supplier the outcome could be interpreted as bias. More trialshave been done, most of these did not fulfil any Good Clinical Practice (GCP)guidelines (International Conference on Harmonisation of Technical Requirementsfor Registration of Pharmaceuticals for Human use 1997).To compare the efficacy and safety of Cimicifuga root with placebo in women withclimacteric complaints the following study was done (Frei-Kleiner 2004). It was amulticenter, randomised, placebo-controlled, double-blinded, parallel group studyin 122 menopausal women with over 3 hot flashes a day, treated for 12 weeks. Thetwo main efficacy measures weekly weighted score of hot flashes were severity andnumber. Patients filled in a daily diary to record number and severity of the hotflashes, each day for the whole treatment period. The Kupperman index was assessedat week–2 on screening, week 0 baseline, week 4, 8, 12 (end of treatment).In the primary efficacy analysis no significant difference between black cohoshand placebo could be demonstrated, regarding the two tested main efficacyvariables. However the superiority of Cimicifuga compared to placebo was seen withrespect to symptoms of menopausal disorders in patients with a Kupperman indexover 20. In the active group the Kupperman index decreased by 13 index points, areduction of clinically relevance. The two assessment instruments, the Kuppermanindex and the Menopause rating Scale (see figure below) correlated markedly andproduced similar results.The analysis in the subgroup by intensity of the weekly weighted score of hotflashes showed no difference between active medication and placebo. The conclusionfrom this study is that Cimicifuga is effective for patients suffering frommoderate symptoms as supposed to mild symptoms. The active preparation is superiorto placebo, with a trend towards significance as assessed by the Kupperman index.This is supported by another study (comparable and uncontrolled) which enrolledonly patients with a Kupperman Index of over 20 (Liske et al 2002).The plant extract was well tolerated during the 3 month trial.The trouble with menopausal trials is that women might enter at different stagesof their perimenopause with great variety of symptoms. The trial of Frei-Kleineret al 2004 illustrates the need to categorize the women according to severity ofsymptoms. Women in the trials enter at different stages of their menopause, perior post menopausal. The placebo effect is about an average of 30 %. For someperimenopausal women the natural progression of the menopause will be easy andwon’t have any perimenopausal symptoms at al in others the symptoms may be presentfor years. Severity per individual will vary greatly. The above trial shows that women with and Kupperman Index over 20 benefit most. Therefore one could interpretthis as that perimenopausal benefit the most, since those get the most severesymptoms.The most recent trial (Osmers et al 2005) supported the above finding that blackcohosh is effective in relieving climacteric symptoms especially in earlyclimacteric women (perimenopausal).This was a randomised, multicenter, double blind clinical trial compared theefficacy and tolerability of the isopropanolic extract with placebo. A total of304 patients were receiving 40 mg or placebo daily for 12 weeks. The primaryefficacy measure was the change form baseline on the Menopause Rating scale,secondary measures included were changes in the sub scores and safety variables.The effect size was 0.03-0.05 menopausal Rating Scale units, similar to HRTresults. Women in the early climacteric phase benefited most, the hot flush subscore was the most effective measure. No adverse effects were found.The two trials have shown the benefit in reducing the Kupperman Index andMenopausal Rating Scale. HRT has been used to prevent osteoporosis, couldCimicifuga Racemosa have any effect on bone density?A study by Wutke et al 2003, was comparing Cimicifuga racemosa with HRT andplacebo, looking at climacteric complains and effects on vagina and bonemetabolism and effect on the uterus. A double blind, placebo and estrogencontrolled, multicenter study in parallel groups. Good Clinical Practiceguidelines were applied, and conducted in accordance with the Helsinki declaration(World Medical Association Declaration of Helsinki 1996). This was the first timeCimicifuga racemosa was investigated in a randomised three armed ,double-blind,and GCP controlled. Comparison included placebo and a positive control in the formof Conjugated Estrogens (CE). At start of treatment patients were selected,characteristics concerning age, height, weight, and the intensity of climactericsymptoms were comparable in all treatment groups. Treatment consisted of 40 mg ofherbal drug, or 0.6mg CE, or placebo. Menopausal Rating Scale (MRS) was used asefficacy criterion (Hauser et al 1994).Three main factors in the MRS were compared; Factor one consisted of hot flushes,sweating, heart complaints and sleep disorders, factor two were depressive moods,nervousness, irritability and impaired performance, memory, factor three, weredisorders of sexuality, urinary symptoms, vaginal dryness, joint and musclesymptoms.Hormonal levels were measured as well as the levels of CrossLaps (metabolicproducts of bone-specific collagen-1alpha1marker for bone degradation,) and thelevels of bone-specific alkaline phosphatase (marker for bone formation) (seefigure 2, Wutke et al 2003).A statistically significant improvement of bone metabolism can be seen with CE and
