How does black cohosh work?

How black cohosh works is not known. The possibility that black cohosh exhibits estrogenic activity has been studied but the evidence is contradictory.

A compound recently identified in black cohosh (fukinolic acid) was shown to have estrogenic activity in vitro. Other active compounds appear to include triterpene glycosides (including actein and cimicifugoside), resins (including cimicifugin), and caffeic and isoferulic acids.

Effect on hormone levels

Women who have reached menopause generally have lower levels of estrogen and higher levels of two other hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), than do women who menstruate. Three of four studies show that black cohosh does not affect LH or FSH.

A study of 150 perimenopausal and postmenopausal women using two different doses of black cohosh (Remifemin tablets, 39 or 127.3 mg/day) found that 6 months of treatment caused no changes in LH, FSH, prolactin, estradiol, or sex-hormone-binding globulin. Another trial of black cohosh in women with breast cancer found small but insignificant changes in LH levels (in 18 subjects) and FSH levels (in 33 subjects). In the third study, Remifemin (8 mg/day given as four 2-mg tablets) did not affect LH or FSH levels in 15 women who had undergone a hysterectomy who were part of a study comparing black cohosh with several estrogens.

The fourth study, which found an effect of black cohosh on LH levels, was a trial in 110 women with menopausal symptoms. Participants treated with Remifemin (8 mg/day) for 8 weeks had significantly lower average LH levels than did a control group (FSH levels were unchanged). However, the report of this study does not include the participants' hormone levels before the study began, so the two groups may have had different LH levels initially.

In vitro studies used to examine the effect of black cohosh have given contradictory results. Black cohosh had no activity in estrogen receptor (ER) binding assays in Ishikawa (endometrial) and S30 (breast cancer) cell lines. It did not show potent ER binding activity; slightly enhanced the growth of ER-positive breast cancer cells (T47D) but was not tested on ER-negative cells. In another study black cohosh inhibited the growth of T47D (human breast cancer) cells. In ER-positive breast cancer cell line 435, black cohosh resulted in growth inhibition. In ER-positive breast cancer cell line MCF-7, it inhibited estradiol-induced stimulation of cell proliferation in one study but isolated constituents of black cohosh increased proliferation in another.

Effect on the vagina

Because of the marked changes in hormone levels in women who have achieved menopause, numerous modifications occur in the structure and activity of vaginal and uterine tissues. Microscopically, vaginal cells look different after menopause because of decreased estrogen. Studies have been mixed on whether black cohosh affects vaginal epithelium. One placebo-controlled, double-blind trial of black cohosh showed estrogenic changes in vaginal epithelium of menopausal women, but another study of two Remifemin doses (39 or 127.3 mg/day) found that 6 months of treatment in perimenopausal and menopausal women caused no changes in vaginal cytology.

Effect on the uterus

Menopause is associated with a thinning of the uterine lining (the endometrium). No human studies have adequately evaluated the effect of black cohosh on uterine endometrium.

When uterine weight of immature female mice and growth of ER-positive breast cancer cells (MCF-7) were used to measure the estrogenic effect of black cohosh, black cohosh caused an increase in uterine weight and growth of cancer cells in culture, which the authors said reflected an estrogenic effect. Black cohosh did not exhibit estrogenic effects in a study that measured uterine weight in immature mice and vaginal cell cornification (conversion of cells from columnar to squamous) in ovariectomized rats.