Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D. The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol. February 28, 2013; [epub ahead of print]. doi: 10.1016/j.jsbmb.2013.02.007.

Concerns about the safety of hormone replacement therapy (HRT) have stimulated efforts to find alternative treatments for adverse menopausal symptoms or "climacteric complaints." Phytoestrogens (plant-derived estrogen mimetics) have been shown to have minimal, if any, efficacy and promote estrogen-dependent carcinomas. The ideal plant-based therapy would be devoid of estrogenic effects in the mammary glands and uterus while having beneficial effects on climacteric symptoms and bone health. This paper summarizes the evidence pertaining to the leading non-estrogenic herbal medicine that has been clinically demonstrated to be efficacious in the treatment of menopausal symptoms, black cohosh (Actaea racemosa syn. Cimicifuga racemosa).

In most countries where black cohosh is regulated as a prescription medication (i.e., countries in Europe), health authorities require that black cohosh not be taken by patients with estrogen-dependent tumors. This is primarily due to a study published in 1985 that said that the estrogenic isoflavone formononetin was found in a black cohosh extract. This finding was never confirmed in subsequent analyses. Isoflavones stimulate the growth of estrogen-dependent cancer cells in vitro and stimulate uterine growth in vivo. Newer studies have used high-performance liquid chromatography (HPLC) to try to identify formononetin in black cohosh extracts. These analyses demonstrated that formononetin was not present in the various extracts tested.

According to the authors, there is ample evidence that extracts of black cohosh do not contain estrogenic compounds—they do not bind to alpha or beta estrogen receptors. Black cohosh dose-dependently inhibited the proliferation of estrogen-dependent cancer cells in vitro, and inhibited estradiol-stimulated proliferation of estrogen-dependent cancer cells and estrogen-receptive endometrial cancer cells. Moreover, animal studies have demonstrated that: (1) black cohosh extracts did not have estrogenic actions in the mammary gland, (2) oral black cohosh inhibited typical mammary tumors in rats, and (3) uterine weight and endometrial thickness (which increase in response to estrogens) remained unaffected in rats treated with oral black cohosh.

In humans, 12 months of black cohosh treatment did not affect mammary gland density, and 12 weeks of treatment did not alter mammary gland cell morphology or proliferation (dosages not reported). A case-controlled study of 949 patients with breast cancer revealed that black cohosh had a significant breast cancer protective effect (study details not provided). In addition to these studies evaluating mammary tissue, 2 studies demonstrated that black cohosh (treatment durations: 1 year or 3 months; doses not reported) had no effect on endometrial thickness. The authors conclude that black cohosh has no estrogenic effects on the endometrium and poses no risks for the uterus.

The authors briefly describe 6 randomized, placebo-controlled studies conducted in Europe that demonstrated that black cohosh decreases climacteric complaints; these studies evaluated German/Swiss extracts of black cohosh produced in accordance with pharmaceutical quality standards. They also reference 2 studies conducted in the United States (US) that concluded that black cohosh had no significant effect on climacteric complaints and the authors suggest two possible explanations for these negative results: (1) the US trials used a much higher dose than the European studies, and (2) possible adulteration of the US study material. They point out that black cohosh products in the American market are sold as food supplements and not pharmaceuticals, and studies have found that some black cohosh supplements contained Asian species of Cimicifuga which have different pharmacological effects, as well as other adulterants. They also describe a third US study which found that black cohosh extract standardized to 2.5% triterpenes was efficacious, while a triterpene-free extract was ineffective.

The authors conclude that the preponderance of evidence indicates that black cohosh has beneficial effects on climacteric complaints without having adverse estrogenic effects on mammary gland or uterine tissue. They emphasize that this lack of an estrogenic effect on peripheral tissue should not be confused with data that demonstrate that black cohosh has an estrogen-like effect on central nervous system neurotransmitters. Most of the studies described evaluated a proprietary, aqueous/ethanolic extract of black cohosh called BNO 1055^® (Bionorica SE; Neumarkt i.d.OPf., Germany). The authors conclude that the black cohosh extract BNO 1055 may be a good non-estrogenic alternative for the treatment of climacteric complaints in menopausal women, including patients with breast cancer.