The use of black cohosh to treat symptoms of menopause☆

Dosage 

The average recommended dose of the crude drug is 40–80 mg (or the oral dose equivalent) of black cohosh per day. The daily dose of dried rhizome and root is 40 mg to 200 mg; a decoction of 240 mL boiling water poured onto 40 mg to 200 mg of black cohosh (crude drug), simmered for 10 to 15 minutes; or 5 to 30 drops of a 1:1 (g/mL) fluid extract, 90% alcohol.

Clinical studies performed before 1996 used doses of 48–140 mg of black cohosh extract per day. A more recent clinical study compared two different dosages of Remifemin—40 mg vs. 127 mg daily—for 6 months and found similar safety and efficacy profiles for both dosages (1). The current recommendation of 40 mg per day was based on the results of this trial (2). However, the dosage used in most clinical trials to date is 80 mg daily of black cohosh extract (see Table 1). Nine of the 10 studies cited in Table 1 found that black cohosh did relieve menopausal symptoms.

Table 1. Clinical Studies on Black Cohosh (Actaea racemosa L., syn. Cimicifuga racemosa)

	*Author/Year	Subject	Design	Duration	Dosage	Preparation	Results/Conclusion
	Jacobson et al., 2001	Menopausal symptoms: Hot flashes in women with history of breast cancer	R, DB, PC n=69 (randomized based on current tamoxifen use)	2 months	One, 20 mg tablet, 2 × daily with meals	Remifemin®	Although both treatment and placebo groups self-reported declines in number and intensity of hot flashes, black cohosh was not found to be statistically more harmful or beneficial than placebo in treating menopausal symptoms. Sweating was the only symptom that did show significantly greater improvement over placebo in the black cohosh group (p = 0.04). Subset analysis showing effects on patients taking tamoxifen was not reported.
	Liske and Wüstenberg, 1998	Menopause complaints	R, DB n = 152 (women ages 43–60 with climateric complaints)	6 months	40 mg/day (crude drug) vs. 127 mg/day (crude drug)	Remifemin®	Decrease in the Kupperman-Menopause Index (KPI) (values -31 at the beginning) was observable after 2 weeks of Remifemin® therapy. Similar results in safety and efficacy were observed for both dosages. After 6 months, a positive response (KPI < 15) was seen in −90% of patients. No detectable changes were seen in hormone levels of LH, FSH, SHBG, prolactin, or estradiol. Remifemin® did not influence vaginal cytological parameters (degree of proliferation). The authors concluded that Remifemin may act as a selective estrogen receptor modulator (“Phyto-SERM”) (no statistics presented).
	Düker et al., 1991	FSH and LH levels during menopause	PC n = 110 female patients with menopausal-complaints who have received no hormonal therapy for at least 6 months (mean age = 52)	2 months	8mg/day extract vs. placebo	Remifemin® tablet vs. placebo	Remifemin® showed an estrogen-like mode of action with selective LH suppression in menopausal women. No significant change in FSH was observed. Mean LH levels significantly reduced compared to placebo (p < 0.05).
	Lehmann-Willenbrock and Riedel, 1988	Menopause complaints	R, Cm n = 60 randomized into 4 treatment groups (Estriol, conjugated estrogen, estrogen gestation, black cohosh)	6 months	1 mg tablet/day Ovestin® or 1.25 mg tablet/day Presomen® or 1 tablet/day Trisequens® r 48–140 mg/day Remifemin®	Ovestin®, Estriol alone; Presomen®, conjugated estrogens; Trisequencs®, combined estrogen-gestagen theapy; Remifemin® tablet	Remifemin® extract was shown to produce a decline in modified KPI and improvement of complaints associated with postoperative ovarian function deficiencies. No significant differences were noted among treatment groups. No differences in LH or FSH levels were observed.
	Pethö, 1987	Menopause complaints	O n = 50 (female patients converting from hormonen injections to black cohosh over 6 months)	6 months	48–140 mg/day	Remifemin® tablet	Hormone replacement therapy (Gynodian, injection) may be switched to black cohosh extract with equivalent success. Of the patients, 82% reported black cohosh preparation good or very good; 56% of patients did not require additional hormone injections. No side effects were noted. Significant improvement in mean menopausal index after 2 months (p < 0.001).
	Stoll, 1987	Menopause complaints	R, DB, PC, Cm n = 80 female patients (ages 46 to 56)	12 weeks	48–140 mg/day or 0.625 mg CE/day + 3 placebo tablets/ day on days 1–21, then 2 placebo tablets 2x/day on days 22–28 or 2 placebo tablets 2x/day	Remifemin® tablet of conjugated estrogens (CE) or placebo	Patients treated with Remifemin® showed significant increase in proliferation status of vaginal epithelium compared to those patients treated with estrogens or placebo (p < 0.001) and significant improvements in somatic and psychological parameters (p < 0.001) (measured by KPI and HAMA scales). The number of hot flashes dropped from average of 4.9 daily to < 1 in black cohosh group; estrogen group, dropped from 5.2 to 3.2 average daily; and placebo dropped from 5.1 to 3.1 average daily occurrences. Improvements in vaginal lining were so significant, author suggests that black cohosh extract is suited as a remedy of first choice to treat menopausal symptoms, particularly if HRT is contraindicated or not desired by patient. Significant improvement of proliferation of vaginal epithelium with Remifemin®, compared to other groups (p < 0.001).
	Warnecke, 1985	Menopause complaints	O, C, Cm n = 60 female patients with menopausal complaints (average age 54 years)	12 weeks	48–140 mg/day or 0.6 mg/day or 2 mg/day	Remifemin® drops or Conjugated estrogens or diazepam	Patients showed similar cytological responses (measured by proliferation and maturation of vaginal epithelial cells) to Remifemin® and estrogens. Patients receiving diazepam had no observable cytological changes. Comparable improvements in neurovegetative and psychological symptoms (measured by Self-Assessment Depression scale, Hamilton Anxiety scale (HAMA), and Clinical Global Impressions scale) were seen in all 3 treatment groups. - retrospective cross-sectional, RS - retrospective, S - surveillance, SB, - single-blind, SC - single-center, U - uncontrolled, UP - unpublished, VC - vehicle-controlled.
	Vorberg, 1984	Menopause complaints	O n = 50 menopausal women (39 patients showed contraindications to HRT, and 11 refused hormone treatment)	12 weeks	48–140 mg/day	Remifemin® drops	Improvements in psychological symptoms, KPI (p < 0.001). Profile of Mood States (POMS) (p < 0.001), and Clinical Global Assessment scale (CGI) (p < 0.001) were all significant to highly significant in treatment group. No serious side effects were observed. Only mild gastrointestinal disturbances, which did not require discontinuation of treatment, were observed.
	Daiber, 1983	Menopause complaints	O n = 36 menopausal women; hormone replacement therapy was refused or contraindicated for these subjects (ages 45–62 years)	12 weeks	48–140 mg/day	Remifemin® drops	Highly significant decreases in KPI were observed, as was improvement in psychological symptoms including decreases in weariness and despondency, and increases in motivation and positive mood. A positive response in the CGI scale was also observed. No side effects or incompatibility reactions were observed during the 12 weeks of administration. Reduction of hot flashes (p < 0.001), nervousness (p < 0.001), depressive psychosis (p < 0.01).
	Stolze, 1982	Menopause complaints	O, MC n = 704 female patients, 629 evaluated (mean age 51 years)	6 to 8 weeks	48–140 mg/day	Remifemin® drops	Significant improvements in neurovegetative complaints and psychological disturbances were experienced by 3 of 4 patients after 4 weeks of Remifemin® therapy. After 6 to 8 weeks, 40–50% of patients experienced complete relief from symptoms and another 30–40% of patients reported marked improvement in symptoms. The Remifemin® was well-tolerated, with no discontinuation of therapy. Only 7% of patients reported mild, transitory nonspecific complaints. In 72% of cases, physicians observed advantages of Remifemin® over previous hormonal treatment. In 54.3% of the cases, physicians stated advantages of Remifemin® compared to previous treatment with psychoactive drugs. No statistics provided.

KEY: C - controlled, CC - case-control, CH - cohort, CI - confidence interval, Cm - comparison, CO - crossover, CS - cross-sectional, DB - double-blind, E - epidemiological, LC - longitudinal cohort, MA - meta-analysis, MC - multi-center, n - number of patients, O - open, OB - observational, OL - open label, OR - odds ratio, P - prospective, PB - patient-blind, PC - placebo-controlled, PG - parallel group, PS - pilot study, R - randomized, RC - reference-controlled, RCS - retrospective cross-sectional, RS - retrospective, S - surveillance, SB, - single-blind, SC - single-center, U - uncontrolled, UP - unpublished, VC - vehicle-controlled.

Commission E has recommended that black cohosh be taken for only a 6-month period However, the Commission has stated that the reason for this limitation on black cohosh is the desire to ensure that women continue to have regular physical examinations at 6-month intervals, rather than concerns about the long-term safety of black cohosh. Although no studies have been done to date on the safety of long-term use of black cohosh, findings of short-term studies using high doses of the herb indicate that it may be considered safe for long-term use 2, 3.

Black cohosh root has been approved by the German Commission E as a nonprescription drug to treat premenstrual discomfort, dysmenorrhea, and neurovegetative menopausal symptoms such as hot flashes, heart palpitations, nervousness, irritability, vertigo, sleep disturbances, perspiration, and depression.

How does black cohosh work? 

Fig. 1 The mechanism by which black cohosh acts is yet undetermined. Some early studies have found it to have estrogenic activity, whereas others have refuted this hypothesis. In one study, three alcoholic fractions produced endocrine effects that inhibit the secretion of luteinizing hormone (LH), but not that of follicle-stimulating hormone (FSH). The authors of this study concluded that black cohosh was exhibiting an estrogen-like effect (4). However, a good-clinical-practices compliance study in postmenopausal women found no estrogen-like suppression of either LH or FSH. In addition, prolactin levels were not affected, no estrogenic changes in vaginal cytological parameters were observed, there was no increase in endometrial thickness, no changes in vaginal cell status, and no changes in the hormone values of LH, FSH, prolactin, and estradiol following treatment with black cohosh 1, 5. Another study found LH suppression with the use of black cohosh, but did not detect estrogen-like uterine effects or changes in vaginal cytology. The authors, therefore, concluded that in this case, LH suppression was associated with neurotransmitter interference rather than estrogenic activity (6).

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Fig. 1. Black cohosh.

Contraindications and adverse effects 

At present there are no known contraindications to the use of black cohosh 3, 7. Whether or not is can be assumed safe in women with breast cancer remains in question. When black cohosh was assumed to have estrogen-like effects, it was contraindicated for women with estrogen-receptor-positive breast cancer; however, subsequent studies found that black cohosh is not estrogenic and this contraindication was not warranted. But a recent study in mice found that although the herb did not increase breast cancer, it did increase the incidence of metastasis in the mice with breast cancer that ingested black cohosh in their diets. Therefore, women with a history of breast cancer should seek the advice of their physician prior to taking black cohosh. Because of the herb's possible estrogenic effect, it is not recommended for use during pregnancy.

The only known adverse effect of black cohosh is occasional gastrointestinal discomfort. Vertigo, headache, nausea, vomiting, impaired vision, and impaired circulation have been reported with overdose. There are no known drug interactions with black cohosh; minimal side effects were noted when black cohosh was taken at the same time as estrogen replacement therapy.

Supplementary data