Black cohosh may be helpful for menopausal symptoms but should not be used for longer than 6 months. Long-term effects on breast and endometrium have not been established.

[LFODPKM ] Letter Key

Latin Name

Cimicifuga racemosa (L.) Nutt. or Actaea racemosa L.

Family

Ranunculaceae

Other Common Names

Black snakeroot, bugbane, bugwort, rattleroot, rattletop, rattleweed, macrotys

Description

• Black cohosh is a perennial woodland plant with small white flowers arranged in spikes.
• Native to North America, it also grows in Europe and north Asia.
• It was used in North American Indian medicine. Insects avoid it, which accounts for some of its common names.

Part Used

Root, rhizome

Known Active Constituents

• Formononetin, a phytoestrogen, was reported in a methanol extract of the dried rhizome of C. racemosa (1); more recent analyses have not identified formononetin (2).
• A recently identified compound, fukinolic acid (2-E-caffeoylfukiic acid) is estrogenic (see animal/in vitro toxicity) (3). Other apparent active compounds are triterpene glycosides (including actein and cimicifugoside), resins (15% to 20%, including cimicifugin), caffeic, and isoferulic acids (4).

Mechanism/Pharmacokinetics

• It is unclear whether black cohosh is estrogenic (see animal/in vitro estrogenicity studies). In humans, a resinous component, acteina, reportedly causes peripheral vasodilation and increased peripheral blood flow in patients with peripheral arterial disease (5).

[Outline]

• LLatin Name
• FFamily
• OOther Common Names
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CO ] Letter Key

Clinical Trials

• Hot flashes, menopausal symptoms
  • A recent randomized, double-blind, placebo-controlled trial in 85 breast cancer survivors (69 completed) found that black cohosh reduced excessive sweating but not hot flashes. Subjects (59 on tamoxifen) took one tablet twice daily of placebo or black cohosh (Remifemin, not identified as such in the article) for 2 months. (6). Hot flash frequency and intensity decreased in both groups with no significant difference between groups. Excessive sweating decreased significantly more in the treatment group than in the placebo group. Other symptoms (palpitations, headaches, poor sleep, depression, irritability) improved equally in both groups; health and well-being scores did not change in either group. Two months is relatively short for this kind of trial.
  • A 6-month treatment-controlled study in 60 women who had undergone hysterectomy but maintained at least one ovary compared Remifemin to three estrogen regimens: estriol (1 mg/day), conjugated estrogens (1.25 mg/day), or estrogen-progestin therapy (estradiol 2 mg and norethisterone acetate 1 mg) (7). Black cohosh was equivalent to the other treatments at 4, 8, 12, and 24 weeks, as measured by a modified Kupperman index.
  • Another randomized, placebo-controlled trial in 80 menopausal women compared Remifemin (4 tablets/day) to placebo or conjugated estrogens 0.625 mg/day (8). At 12 weeks, Kupperman index and Hamilton anxiety scores were significantly lower in the treated groups compared with the placebo group; black cohosh was somewhat better than estrogen treatment. This is one of the few studies that asked women about hot flashes separately from other symptoms. Daily hot flashes decreased from 4.9 to 0.7 in the Remifemin group, from 5.2 to 3.2 in the estrogen group, and from 5.1 to 3.1 in the placebo group.
  • An open, randomized, 12-week study of 60 women compared Remifemin liquid (40 drops b.i.d.) to conjugated estrogens 0.625 mg/day or diazepam 2 mg/day. All treatments improved the Kupperman index, a depression scale, and an anxiety scale (9).
  • A 6-month study testing two different doses of black cohosh extract (40 mg or 127 mg/day) found no advantage to the higher dose (10).
• Hormone levels
  • Three of four studies show that black cohosh does not affect luteinizing hormone (LH) or follicle-stimulating hormone (FSH). A 6-month study of 152 women using different doses of Remifemin tablets (40 mg or 127 mg/day) found no changes in LH, FSH, prolactin, estradiol, or sex hormone binding globulin (11). The Jacobson trial found no change in LH or FSH levels in 51 participants who underwent blood tests (6). Remifemin 4 tablets/day did not affect LH or FSH levels in the Lehmann-Willenbrock study (7).
  • Only one trial, in 110 women with menopausal symptoms, found that those treated with Remifemin (8 mg extract/day 8 weeks) had significantly lower mean LH levels than a control group; FSH levels were unchanged (12). However, the report of this study does not include levels of hormones drawn before the study began, so the two groups may have had different baseline LH levels.
• Vaginal effects
  • One placebo-controlled, double-blind trial of black cohosh in 80 women showed estrogenic changes in vaginal cells at 12 weeks (8), but another study of different doses of black cohosh (40 mg or 127 mg/day) in 152 women found no changes in vaginal cells at 6 months (10).

Other Claimed Benefits/Actions

• Labor preparation, induction, and facilitation (specifically strengthening or restarting contractions)
• Cough
• Induction of menses
• Dysmenorrhea
• Premenstrual syndrome
• Rheumatoid arthritis
• Sciatica
• Tinnitus
• Sedative

[Outline]

• CClinical Trials
  • Hot flashes, menopausal symptoms
  • Hormone levels
  • Vaginal effects
• OOther Claimed Benefits/Actions

[AP ] Letter Key

Adverse Reactions

• Adverse birth outcome
  • Neurologic complications were reported in a post-dates baby after labor induction with a mixture of black cohosh and blue cohosh given during a home birth (13). After a normal labor, a 3,840 g female was born with no spontaneous breathing. Mechanical ventilation was necessary, and hypoxic injury of the basal ganglia and parasagittal area was demonstrated by computed tomography (CT) scan; at 3 months of age, the baby had lower limb spasticity and required nasogastric feeds. Blue cohosh, which contains the vasoconstrictive and oxytocic glycoside caulosaponin, is more likely to be associated with this adverse event than black cohosh.
• Endometrial hyperplasia
  • The Jacobson study notes one case each of endometrial hyperplasia, vaginal bleeding, hysterectomy, and dilation and curettage (D&C) among black cohosh-treated women (all were also taking tamoxifen) (6). Although vaginal bleeding and endometrial hyperplasia have been associated with tamoxifen, no information is provided that would reassure the reader that black cohosh did not contribute to the adverse event (see questions and answers).
• Other
  • One case of arrhythmia (not otherwise defined, but classed as a "minor" adverse event) was reported in a trial of black cohosh in a black cohosh-treated patient who was not taking tamoxifen (6).
  • Black cohosh can cause stomach discomfort or frontal headaches (4).
• Estrogenicity studies (Animal/In vitro)
  • Increased uterine weight was seen in two studies of ovariectomized mice given black cohosh (14,15); two other studies showed no estrogenic effects in either mice given oral doses (16,17) or rats given injected doses (16).
  • In vitro studies are mixed, but most show no estrogenicity. Recent tests of black cohosh in in vitro assays showed no estrogenic activity (17,18,19). Six in vitro cell culture studies (two reported only as abstracts) found that extracts of black cohosh did not stimulate the growth of breast cancer cells (17,19–23); four found inhibition of growth at some doses (19,21–23). Two other studies found that black cohosh significantly increased the growth of breast cancer cells compared with untreated control cells. One found that the effect was similar to 17 beta-estradiol (14). Another study (reported as an abstract), found that ethanolic extracts of black cohosh (0.1 to 10 µg/mL) significantly increased the number of MCF-7 cells; a higher 100 µg dose had no effect (24). Adding an estrogen antagonist (ICI 182,780) abolished the proliferative effect of black cohosh. A constituent of black cohosh, fukinolic acid, increased growth of MCF-7 breast cancer cells; again, the effect was similar to estradiol (3).
  • The only in vivo study identified (reported as an abstract) tested Remifemin in five groups of rats with DMBA-induced mammary tumors (25). Rats were ovariectomized after 5 to 9 weeks of neoplastic growth, and then were given no treatment, oral mestranol (450 µg/kg), or Remifemin in doses equivalent to 1×, 10×, or 100× human dosage. Ovariectomy caused tumor regression in all animals; mestranol but not black cohosh increased tumor growth after ovariectomy. No estrogenic effects were noted on histologic examination of uterine tissue; prolactin, FSH, and LH were unaffected. Conclusions cannot be drawn from this abstract without seeing a more complete presentation of data.

Pregnancy/Lactation

• May precipitate labor
• See also adverse effects

[Outline]

• AAdverse Reactions
  • Adverse birth outcome
  • Endometrial hyperplasia
  • Other
  • Estrogenicity studies (Animal/In vitro)
• PPregnancy/Lactation

Common Dosage Forms

• Dried root or rhizome: 40 to 200 mg/day.
• Liquid extract: (1:2) 1.5 to 3.0 mL/day.
• Tincture: (1:10, 60% ethyl alcohol) 0.4 to 2 mL/day (or equivalent to 40 mg root or rhizome/day) (4).
• Ointments or salves containing black cohosh have also been used.
• Commercial black cohosh preparations are usually standardized to triterpene saponins that include actein and cimicifugoside.
• Remifemin contains 20 mg of black cohosh extract per tablet and is standardized to 1 mg triterpenes, calculated as 26-deoxyactein (erroneously reported in many sources as 27-deoxyactein) per tablet. The current recommended dose is 20 mg twice daily. Note: Both the formulation and dosage of Remifemin have changed over time. First a liquid, now tablets, the dosage of extract in each tablet has increased from 2 mg to 20 mg. Studies done with earlier versions may not be applicable to the current version.

Q: Is it safe to use black cohosh indefinitely?

A: Black cohosh traditionally has not been used long term, and all published studies have only followed women for 6 months or less. There are no adequate published human data regarding long-term safety. Two studies, published only as abstracts, note no change in endometrial thickness, but longer, adequately reported studies must be done.

One study administered Remifemin, approximately 136 mg/day for a mean of 98 days, to 28 postmenopausal women (26); the second administered Cimicifuga extracts (otherwise unidentified) to 50 postmenopausal women for 6 months (27). Neither noted a change in endometrial thickness. In vitro and in in vivo estrogenicity tests are mixed. Although no cases of endometrial carcinoma have been reported, I am concerned about unopposed stimulation of the endometrium with long-term use. Phytoestrogens in black cohosh are not the same as phytoestrogens present in beans and grains and may not be as benign.

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