Latin name; Cimicifuga racemosa
Pharmacopoeial name: Cimicifugae racemosae rhizome
Other names; black snake root, rattleroot
About Black Cohosh
Cimicifuga racemosa is a summer plant of the deep woods and forest margins, reaching up to 6 or even 8 feet tall. The herbaceous plant has feathery white blossoms, 1 to 3 feet long. The fruits are dry. The roots and rhizomes of Cimicifuga racemosa have been widely used in the treatment of menopausal symptoms and menstrual dysfunction throughout Europe since the early to mid 19th century. Traditionally the root is antispasmodic, anti-inflammatory, analgesic, emmenagogue, anti-rheumatic and sedative. The plant is a traditional herbal remedy of the North American Indians where it was used mainly to treat women’s problems, especially painful periods and problems associated with the menopause (1,2).
The extract contains: Triterpene glycosides such as actein, cimicifugoside and cimigenol, organic acids, such as cimicifugic acid, ferulic acid and isoferulic acid. At present the pharmacological actions of the dry extract cannot be definitively ascribed to one or a group of these constituents. It is not therefore possible to standardise the extract to active constituents, but rather marker constituents that are always present in the extract. The assay of the extract is carried out by determination of the content of cimicifugic acids (calculated as caffeic acid) which serves in this way as an analytical marker which must fall within certain specifications in order for batch-to-batch release and for stability testing of the tested and released tablets. The peak area of the analytical marker in the chromatogram of the drug product and in the chromatogram of the Cimicifuga rhizome dry extract used for the manufacture of the respective batch of drug product are compared with each other and the results are evaluated. Furthermore, within stability testing the content of cimicifuga acid B (calculated as caffeic acid) in the dry extract and the finished product are determined at every point of testing throughout the shelf life of the product.
Clinical trials of aqueous-alcoholic extracts of Black Cohosh rhizomes using standardised and internationally recognised validated measurement scales have helped to identify benefit relating to individual symptoms. These methods also provide general information about the degree of severity of the vasomotor, psychological and somatic symptoms by means of the total score. Climacteric symptoms are most often determined using the so called Kupperman Menopause Index, in which symptoms that subjects find particularly troublesome are given a certain weight by a high multiplier. Adding the numbers which result for each symptom produce the menopause index which measures the severity of the climacteric symptoms (3).
The exact mechanism of action of Black Cohosh is still not completely understood. This is why there is no universally recognised method by which the marker compounds are standardised (4). It used to be thought that Black Cohosh was indirectly oestrogenic and had an effect on the central nervous system involving certain neurotransmitters. However more recent studies have demonstrated non-oestrogenic and even anti-oestrogenic or anti-proliferative effects in breast and prostate cells lines. Black Cohosh is also thought to be dopaminergic, serotonergic, antioxidant and anti-inflammatory (4,5).
A number of in vitro and in vivo studies have demonstrated conflicting evidence for oestrogenic activity of Black Cohosh extracts. Some in vitro and in vivo studies have demonstrated a non-oestrogenic effect showing that it does not promote cell proliferation in a number of oestrogen mediated cancer cell lines (5-7). Furthermore, in some cases, the extract has inhibited cell proliferation of breast cancer cell lines (5,8,9). Further studies have shown that Black Cohosh does not induce cell proliferation in breast, vaginal and endometrial tissues which would suggest a lack of oestrogenic activity (10-13). A recent clinical trial has also demonstrated both safety and efficacy of Black Cohosh in breast cancer survivors on Tamoxifen maintenance therapy (14).
Conversely however, there is some evidence that a sub-fraction of Black Cohosh extract has oestrogenic like effects as assessed by in vivo, ex vivo and in vitro assays (15). Some in vitro and in vivo studies have demonstrated dopaminergic, serotonergic, antioxidant and anti-inflammatory actions (4,6,16). The ambiguous and contradictory nature of the evidence concerning whether Black Cohosh exerts a clinically relevant oestrogenic effect has led to the regulatory requirement that Black Cohosh must be contra-indicated in women who have, or have had, an oestrogen dependent tumour.
Black Cohosh is one of the most widely researched natural products for the treatment of menopausal symptoms. Numerous uncontrolled and seven controlled studies have been carried out demonstrating efficacy against placebo in mild to moderate vasomotor symptoms especially when the symptoms also include sleep and mood disturbances
(17,18). The following demonstrate the efficacy of Black Cohosh for the treatment of menopausal symptoms and two study summaries demonstrate the efficacy of the combination of Black Cohosh and St John’s Wort.
Otkem et al performed an investigational trial of Black Cohosh compared with Fluoxetin in 120 health post-menopausal women for 6 months(19) Kupperman Index and Beck’s Depression Scale. Results decreased significantly in both groups by the end of 3rd month. However by the end of 3rd month Kupperman Index results decreased more significantly in the Black Cohosh group compared with the Fluoxetine group. By the end of the 6th month Black Cohosh reduced hot flushes scores by 85% with Fluoxetine by 62%
A prospective, multi-centre, randomised, placebo-controlled, double-blind, parallel study examined Black Cohosh dried ethanolic root extract in 122 peri – or early menopausal women for 12 weeks (20). Weekly weighted score of hot flushes showed 37% decrease with Black Cohosh and 30% with placebo. Kupperman Index results showed 26% decrease with Black Cohosh and 17% with placebo. However the sub-group of the patients who had at least moderate menopausal symptoms in the Kupperman Index (≥20) showed a decrease of 47% in the Black Cohosh group with 35 patients when the reduction in the placebo group with 18 patients was 21%. The weekly weighted scores of hot flushes decreased by 53% in the Black Cohosh group and 25% in the placebo group. Also regarding the Menopause Rating Scale the score values decreased by 48% in the Black Cohosh group and 14% in the placebo group, the former showing significant superiority.
A controlled, randomised, double-blind, parallel group study of 150 peri-and post-menopausal women with at least moderate severity of symptoms over 24 weeks identified there were no significant differences between low and high dose groups in the primary measures (21). However the decrease of symptoms was 70% in the standard dose group and 72% reduction in the high dose group. The Self rating depression scale demonstrated a median score decrease from 44.5 to 37 in the standard dose group and from 44 to 36 in the high-dose group, reflecting an improvement in the state of menopausal depression.
Briese et al. performed a prospective, controlled, open, observational study of Black Cohosh dry root extract 3.75 mg or Black Cohosh dry root extract 3.75 mg and St John’s Wort extract/tablet 70 mg in 6141 women (3027 monotherapy, 3114 combination therapy) over 6-12 months (22). The symptoms scores improved from baseline in both groups. The depression (MRS) with and menopause rating (PSYCHE) scores were significantly reduced in both groups at 3 months and at 6 months. The combination treatment showed superiority over Black Cohosh alone especially in menopausal mood symptoms.
A 16 week double-blind, randomised, placebo-controlled study of Black Cohosh dry root extract 3.75 mg and St John’s Wort extract 70 mg per tablet, in 301 women over 16 weeks, found Menopause Rating Scale Score decreased 50% in the active group against 19.6% in the placebo group (23). Also the Hamilton Depression Rating Scale total score decreased 41.8% in the active group and 12.7% in the placebo group, showing that the treatment was significantly superior to placebo. The combination of Black Cohosh and St John’s Wort showed efficacy in alleviating menopausal symptoms with psychological complaints.
Although Black Cohosh is regarded as a safe alternative to HRT for the treatment of mild menopausal vasomotor symptoms such as hot flushes and night sweats, there have been rare reports in the literature of hepatotoxicity that may be associated with Black Cohosh use, although causality has not been proven. The increasing popularity of Black Cohosh as a first line treatment to relieve menopausal vasomotor symptoms has resulted in the publication of a number of comprehensive reports assessing this hepatotoxicity causality issue. It has been concluded by many experts that none of the reported cases found hepatotoxicity causality proven (24). Some authors have suggested that liver damage in the reported cases was possibly caused by over-dosage, source of the plant, incorrect species, poor quality or combination preparations (4,25,26).
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