Summary

Black Cohosh is a plant that is native to North America. Originally Native Americans used the fresh or dried root for several different medicinal purposes. Folk medicine used this root to help with gynecological issues related to symptoms of PMS and menopause. It can also be used to help sore throats, depression and to soothe achy joints. The clinically approved purpose is to help with symptoms of PMS. Black cohosh use during pregnancy and breast-feeding is not advised. It also shouldn’t be used during estrogen-based hormone replacement therapy. Consumers should use caution when combining black cohosh with azathioprine, cyclosporine, antihypertensives, tamoxifen, and iron-containing products. Taking 5 grams or more can lead to vomiting, headache, dizziness, limb pain, and hypotension. Black cohosh can be found in tablet, capsule, drops and solution form.

Description

Medicinal Parts

The medicinal part is the fresh and dried root.

Flower and Fruit

The inflorescence is a long-peduncled, drooping raceme, 30 to 90 cm long with white flowers. There are 3 to 8 petals without nectaries, and the sepals enclose the flower bud.

Leaves, Stem, and Root

The plant grows 1 to 1.5 m high. It is leafy, with a sturdy, blackish rhizome, which is cylindrical, tough, and knotty. The straight, grooved, dark-brown roots sprout from the underground rhizome and are roughly quadrangular. The transverse root section shows wedge-shaped bundles of white wood. The rhizome section shows a large black medulla surrounded by a ring of paler, woodier wedges. The leaves are double-pinnate, smooth, and crenate-serrate.

Habitat

Black Cohosh is native to Canada and the U.S.; it is cultivated in Europe.

Production

The medicinally used part of the plant consists of the dried rhizome of Cimicifuga racemosa with attached roots.

Other Names

Black Snake Root, Bugbane, Bugwort, Cimicifuga, Rattleroot, Rattleweed, Richweed, Squaw Root

Actions & Pharmacology

Compounds

Triterpenes: triterpene glycoside, including actein, 27-deoxyactein, cimifugoside

Quinolizidine alkaloids: cytisine, methyl cytisine

Phenylpropane derivatives: including isoferulic acid

Effects

The active ingredients in the root are the triterpine glycosides such as cimifugaside, 27-deoxyactein, and actein. The increase in luteinizing hormone (LH) that occurs as estrogen levels decrease is implicated as the cause of menopausal symptoms. Compounds of the rootstock of Cimicifuga racemosa bind to the estrogen receptor where it selectively suppresses LH secretion with no effect on FSH. The result is an estrogenic effect, which will decrease climacteric symptoms such as hot flashes, diaphoresis and psychological disturbances (Duker, 1991, Lehmann-Wilenbrock, 1988). The improvement in premenstrual symptoms, dysmenorrheal, and menopause may be due to the relaxing of uterine tissue (Tyler, 1997).

There have been some conflicting reports stating Cimicifuga racemosa has no estrogenlike action (Einer-Jensen, 1996; Liske, 1998). The herb did not appear to have an effect on levels of LH, FSH, sex hormone-binding globulin (SHBG), prolactin, and estradiol in a study that concluded the therapeutic effects seen are not attributable to estrogenic or other endocrine-system effects (Liske, 1998).

Other reported effects in animal trials include analgesic, antidepressant, and anti-inflammatory activities.

Analgesic Effects

Methanol extract of Cimicifuga rhizome demonstrated significant anti-nociceptive activity in rats (Kim & Kim, 2000).

Antidepressant Effects

An extract of Black Cohosh exhibited antidepressant activity when administered to female mice. Tail suspension test (TST) was used as a screening test for antidepressant activity in this study. Black cohosh extract significantly reduced the period of immobility, a result comparable to that of imipramine, another antidepressant drug (Winterhoff et al, 2003).

Anti-Inflammatory Effects

Methanol extract of Cimicifuga rhizome demonstrated significant anti-inflammatory activity in rats (Kim & Kim, 2000). Virus-infected mice were found to have lowered interleukin-8 levels and reduced numbers of exuded neutrophils (obtained by bronchoalveolar lavage) after treatment with ferulic acid, isoferulic acid, or a Cimicifuga extract, as compared to the control group (Hirabayashi et al, 1995).

Hormonal Effects

In vitro data suggest that black cohosh has antagonistic effects on estrogen receptor-positive human breast cancer cells and it may act as a selective estrogen receptor modulator (SERM) (Bodinet & Freudenstein, 2002). An in vitro assay demonstrated antiestrogenic activity from the rhizome of Cimicifuga racemosa. It antagonized estradiol-induced activities in an experimental model (Zierau et al, 2002). At high concentrations, Cimicifuga racemosa inhibited the proliferation of human breast adenocarcinoma cells (MCF-7). In addition, estrogen-induced proliferation of MCF-7 was reduced in the presence of Cimicifuga racemosa extract, an effect that was reversible with increased concentrations of estradiol. Another in vitro study failed to demonstrate any significant binding to estrogen or progesterone receptors as well as estrogenic effect of Black Cohosh (Zava et al, 1998).

Extract of Cimicifuga racemosa in doses up to 100-fold the human therapeutic dose did not exert estrogenic activity in rats with experimentally induced, hormone-responsive mammary tumors. The Cimicifuga racemosa extract did not have a direct effect on uterine tissue proliferation or an indirect effect on pituitary-secreted, estrogen-regulated hormones (Freudenstein et al, 2002). Black Cohosh extract did not promote the growth of an estrogen-dependent breast cancer cell line (MCF-7) in animal cells. Black cohosh did not significantly transactivate through human estrogen receptor (hER)-alpha or hER-beta (Amato et al, 2002).

An extract of Cimicifuga racemosa (CR) exhibited an estrogen-antagonistic effect on estrogen receptor-positive breast cancer cells. At high concentrations, CR inhibited the proliferation of human breast adenocarcinoma cells (MCF-7). In addition, estrogen-induced proliferation of MCF-7 was reduced in the presence of CR-extract, an effect that was reversible with increased concentrations of estradiol. Results from additional studies suggested that CR-extract may act as a selective estrogen receptor modulator (SERM) (Bodinet & Freudenstein, 2002).

Clinical Trials

Cancer

In a pharmaco-epidemiologic, observational, retrospective cohort study, it was shown that women treated with an isopropanolic black cohosh extract were no more likely than women not treated with the herb to experience an increased risk of breast cancer recurrence. The study showed that treatment with black cohosh was associated with prolonged disease-free survival (Zepelin et al, 2007).

The effects of the isopropanolic extract of black cohosh on mammographic breast density and breast epithelial proliferation was evaluated in a prospective, open, uncontrolled drug safety study of healthy postmenopausal women with climacteric symptoms. During the 6- month treatment, no adverse effects on breast tissue were caused by black cohosh extracts and no endometrial or general safety concerns were detected (Hirschberg et al, 2007).

Four hundred postmenopausal women with symptoms related to estrogen deficiency were enrolled in a prospective, open-label, multinational, multicenter study. For one year, participants received a daily special black cohosh extract corresponding to 40 mg of herbal drug. Endometrial safety was determined by assessment of endometrial biopsy samples. After one year, no endometrial proliferation could be found. An improvement of climacteric complaints as well as only few gynecologic organ-related adverse events were reported (Raus et al, 2006).

Menopausal Symptoms

A rigorous, systematic review of placebo-controlled randomized clinical trials of Black Cohosh and other nonhormonal therapies for menopausal symptoms indicated that, while the herb has been studied in numerous trials, the quality of the trials vary widely and results are mixed (Tice, 2007).

Most randomized, placebo-controlled trials of Black Cohosh for relief of menopausal symptoms have been relatively short in duration (12 weeks or less) and somewhat small in terms of participants. In contrast, the Herbal Alternatives for Menopause Trial (HALT), the results of which were published in the Annals of Internal Medicine in 2006, was a comparatively large and lengthy trial. It found that Black Cohosh has little potential as a therapy for relieving menopausal hot flushes or night sweats, neither reducing their frequency or severity—whether used alone or as part of a blend. The 12-month, randomized, and double-blind, placebo-controlled trial involved 351 women who reported two or more hot flashes daily. The participants were randomly assigned to one of three herbal regimens: Black Cohosh 160 mg daily, a multi-botanical preparation containing 200 mg of Black Cohosh plus 9 other ingredients, or multi-botanicals plus increased intake of foods containing soy. Other women were randomized to hormone therapy (estrogen with or without progesterone), or placebo. Neither Black Cohosh nor the other herbal regimens provided any clinically meaningful relief of hot flushes. At 3, 6, and 12 months, participants taking the botanical treatments experienced the same change in hot flushes as those taking the placebo. Those taking estrogen, however, had substantially decreased vasomotor symptoms. The study involved too few people to catch possible small changes in the frequency of hot flashes (fewer than 1.5 per day) (Nelson, 2006).

Similar results for the efficacy of black cohosh for the treatment of hot flashes were obtained in a double-blind, randomized, crossover trial of 132 women. The mean decrease in hot flash score and hot flash frequency was not significantly different between the black cohosh group and placebo. The study failed to provide evidence that black cohosh reduced hot flashes more than placebo (Pockaj et al, 2006).

A review of treatments for menopausal symptoms published in The Lancet in 2005 cites evidence that overall, results of randomized controlled trials do not suggest that Black Cohosh is useful for hot flashes, although there are exceptions. A high-dose of Black Cohosh in women with breast cancer and taking tamoxifen did reduce the number of hot flashes significantly more than those not taking Black Cohosh, for example (Hickey 2005).

Similarly, a discussion on managing menopausal symptoms published in the New England Journal of Medicine in 2006 identified mixed but primarily negative evidence for the effectiveness of Black Cohosh in regard to its ability to improve the frequency or severity of menopausal hot flashes. The author points out that Black Cohosh could possibly bind estrogen receptors and pose the same risk for adverse outcomes that estrogen poses; studies have not been of size or duration to fully document the safety of Black Cohosh (Grady, 2006).

A 2006 update in Alternative & Complementary Therapies notes that while several studies in 2005 and 2006 provide new information on Black Cohosh, two indicated positive effects on menopausal symptoms, while one had mixed results and one indicated no effect at all (Hudson, 2006).

A positive finding for Black Cohosh was reported in a 2006 trial in which the herb was combined with St. John's wort (Hypericum perforatum) in 301 women with menopausal complaints that included a psychological component. The 16-week, double-blind and randomized trial found the combination to be superior to placebo in alleviating the symptoms and the related depression as well, with the Menopause Rating Scale score decreasing 50% in those randomized to the combination treatment as compared to 19.6% of those taking placebo, and the Hamilton Depression Rating Scale decreasing 41.8% versus12.7%, respectively. Each treatment combination tablet contained Black Cohosh extract standardized to 1 mg trierpene glycosides and St. John's Wort extract standardized to 0.25 mg total hypericine; the participants randomized to this group started with a double dose (2x2 tablets per day) for the first 8 weeks of treatment followed by 2x1 tablets per day for the second study phase (Uebelhack, 2006).

Positive results were also demonstrated in a multicenter, randomized, placebo-controlled, double-blind, parallel-group study which investigated the efficacy and safety of the black cohosh root extract Cr 99 in 122 menopausal women with climacteric complaints. The 12-week study demonstrated a superiority of the Cimicifuga racemosa extract compared to placebo in the subgroup of patients with menopausal disorders of at least moderate intensity according to a Kupperman Index of 20 or greater, but not in the intention-to-treat population (Frei-Kleiner et al, 2005).

In a post-marketing surveillance study, 2,016 women (40-65 y) with a Kupperman Index of 20 were treated with an isopropanol extract of Cimicifuga racemosa. Changes of subjective symptoms of menopause were evaluated at the start and at the end of 4, 8, and 12 weeks of treatment. Based on weighted symptom scores, hot flashes, sweating, insomnia, and anxiety decreased significantly. Kupperman Index decreased, on average, 17.64 points (P(.001). Thus, the extract was found to be effective in the alleviation of menopausal symptoms (Vermes et al, 2005).

To investigate the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa on climacteric complaints in comparison with low-dose transdermal estradiol, 64 postmenopausal women were chosen to take part in a 3-month, randomized clinical trial. It was found that Cimicifuga racemosa may be a valid alternative to low-dose estradiol in the management of climacteric complaints, especially in those women who refuse or who cannot be treated with conventional medication (Nappi et al, 2005).

A placebo-controlled, open study was conducted to determine the effects of commercially available Cimicifuga racemosa extract (Remifemin) on LH and FSH secretion in 110 menopausal women. After 2 months of therapy with 8 mg daily of the drug, FSH levels in the Remifemin treatment group and placebo group were similar. LH secretion was significantly reduced in the Remifemin treatment group, which points to the estrogenic effect of Cimicifuga racemosa preparations (Duker, 1991).

There was no difference in the reduction of menopausal symptoms between a standard dose of 39 mg/day Remifemin and a high dose of 127.3 mg/day of Black Cohosh extract administered to perimenopausal and postmenopausal women in a 12-week randomized, double-blind, parallel group study. Neither dose exerted estrogenlike effects to the uterus. At 12-weeks the percentage of patients with a favorable therapeutic response (Kupperman Menopause Index score of less than 15) was 70% and 72% for the standard-dose and high dose groups, respectively (Liske et al, 2002).

Neither conjugated estrogens nor Black Cohosh were different from placebo in reducing menopausal symptoms in a 12-week this double-blind, randomized, placebo-controlled multicenter study; however, Black Cohosh lacked the undesired effects to the uterus seen with conjugated estrogens (Wuttke et al, 2003).

In an open-label study, 60 hysterectomized patients under 40 years of age with at least one intact ovary were involved in a study to determine the effect of Cimicifuga racemosa extract (Remifemen 8 mg), estriol (1 mg), conjugated estrogens (1.25 mg), and an estrogen-gestagen product on menopausal symptoms. Cimicifuga racemosa was as effective as the estrogen products in decreasing menopausal symptoms in young patients who have undergone a hysterectomy (Lehmann-Willenbrock, 1988).

Eighty percent of women experiencing menopausal symptoms improved or resolved in a multicenter study of 629 patients (mean age 51 years) who were treated with Black Cohosh. Patients tolerated the black cohosh well with mild gastrointestinal complaints recorded in 7% of the patients studied. (Stolze, 1982).

Menopausal Symptoms: Breast Cancer Survivors

A significant reduction in frequency and severity of hot flushes in premenopausal breast cancer survivors was observed following a 12-month treatment with Black Cohosh. Severe hot flushes included 5 or more daily episodes of heat, accompanied by sweating, sleep disturbances, irritation, and anxiety. At the end of the 12-month study, 46.7% of participants in the Black Cohosh group were free of hot flushes compared with none in the control group; 24.4% still suffered from severe symptoms compared with the control group (73.9%), and 28.9% experienced moderate symptoms compared to 26.1% in the control group (Munoz & Pluchino, 2003).

Black Cohosh was assessed in a randomized, double-blind, placebo-controlled trial involving 85 women with a history of breast cancer. Both treatment and placebo groups reported decreases in the number and intensity of hot flushes, compared with baseline values. There were no statistically significant differences between the two groups, and a subgroup analysis of tamoxifen users and nonusers did not reveal any statistically significant differences (Jacobson, 2001).

Osteoporosis

Positive effects on bone metabolism were observed in postmenopausal women following a 12-week treatment with Black Cohosh extract. Black Cohosh increased the levels of bone-specific alkaline phosphatase at week 12 (p=0.0358), which is a metabolic marker for bone formation, while the same marker remained unchanged in those received either conjugated estrogen and placebo. Black Cohosh and placebo appeared to increase osteoblast activity. Both Black Cohosh and conjugated estrogen increased serum triglycerides. No other serious adverse reactions were reported (Wuttke et al, 2003).

Indications & Usage

Approved by Commission E:

• Climacteric complaints
• Premenstrual syndrome (PMS)

Unproven Uses

In folk medicine, the plant is used for rheumatism, sore throats, and bronchitis. The tincture is also used as a sedative, for choreic states (involuntary, rapid motions), fever, lumbago, and snakebite. The herb is also available commercially in combination with St. John's Wort for depressive moods associated with premenstrual and menopausal symptoms.

Chinese Medicine

The Chinese have used Black Cohosh for the above indications as well as for measles in the pre-exanthem stage.

Contraindications

Pregnancy

The use of Black Cohosh is contraindicated during pregnancy due to an increased risk of spontaneous abortion.

Breastfeeding

Not to be used during breastfeeding.

Precautions & Adverse Reactions

Cimicifuga racemosa should not be substituted for hormone replacement therapy with estrogen. There is no information to date that the herb contains cardioprotective effects or protective effects against osteoporosis.

Safety beyond use for 6 months is not yet determined (Hickey, 2005). Although no serious health hazards were reported in conjunction with the proper administration of designated therapeutic dosages, there are adverse events associated with the use of Black Cohosh, including gastroenteritis, nausea, and vomiting. A case of muscle damage was linked to the use of Black Cohosh in one individual (Minciullo, 2006).

Drug Interactions

Major Risk

Azathioprine

Concurrent use may result in reduced immunosuppressive drug effectiveness and acute transplant rejection. Clinical management: Black cohosh should not be used concurrently with azathioprine. Advise patients taking azathioprine for transplant maintenance to avoid black cohosh, including herbal teas and combination supplement products containing black cohosh. If patients are found to be taking black cohosh and azathioprine, discontinue black cohosh and evaluate the patient for signs and symptoms of transplant rejection.

Cyclosporine

Concurrent use may result in reduced immunosuppressive drug effectiveness and acute transplant rejection. Clinical Management: Black cohosh should not be used concurrently with cyclosporine. Advise patients taking cyclosporine for transplant maintenance to avoid black cohosh, including herbal teas and combination supplement products containing black cohosh. If patients are found to be taking black cohosh and cyclosporine, discontinue black cohosh and evaluate the patient for signs and symptoms of transplant rejection.

Potential Interactions

Antihypertensives

Black Cohosh can potentiate the effect of antihypertensive medications. Clinical Management: Avoid concomitant use.

Tamoxifen

Cimicifuga racemosa extract may enhance effects of tamoxifen. Under estrogen-deprived conditions, dilutions of CR-extract significantly inhibited human breast adenocarcinoma (MCF-7) cells in vitro. This had an additive effect when combined with tamoxifen (Bodinet & Freudenstein, 2002).

Iron-Containing Products

The tannin content of black cohosh may complex with concomitantly administered iron, resulting in nonabsorbable insoluble complexes. Clinical Management: Patients who need iron supplementation should be advised to separate administration times of these two compounds by a minimum of 2 hours.

Overdosage

An intake of very high dosages of the drug (5 g) or an extract (12 g) leads to vomiting, headache, dizziness, limb pain, and hypotension.

Dosage

Mode of Administration

Galenic preparations for internal use.

How Supplied

• Capsules - 60 mg, 80 mg, 450 mg, 540 mg, 545 mg
• Drops
• Solutions
• Tablets - 60 mg, 120 mg

Daily Dosage

Alcoholic-aqueous extracts (ethanolic-aqueous 40-60% (V/V) or isopropanolic-aqueous 40% (V/V)) corresponding to 40 mg drug. The herb is not recommended for treatment longer than 6 months unless advised by a physician.

Menopause symptoms: 40 to 200 mg daily (powdered rhizome); 0.4 to 2 mL daily (tincture, 1:10 in 60% alcohol).

Hot flushes due to tamoxifen therapy: 20 mg-tablet twice daily.

Literature