The estrogenic effect of black cohosh, dong quai, ginseng, and licorice root was evaluated by (i) an examination of the effect on cell proliferation of MCF-7 cells (a human breast cancer cell line), (ii) transient gene expression assay, and (iii) a bioassay in mice. The authors concluded that dong quai and ginseng stimulate growth of MCF-7 cells independent of estrogenic activity, and that black cohosh and licorice root do not have estrogenic activity or stimulate the breast cell line (68).
Red clover (Trifolium pratense) is a member of the legume family, with brand names including Promensil and Rimostil. It contains at least four estrogenic isoﬂavones and is promoted as a source of phytoestrogens. Red clover is a medicinal herb with no traditional long-term use in menopause. Its estrogenic effects were first discovered by observing its effects on sheep. The term Clover syndrome is used to describe the symptoms frequently seen in sheep that consume large amounts of red clover. This syndrome is characterized by reproductive complications, including infertility. Despite its presumed estrogenic activity, several studies, including two double-blind, placebo-controlled trials, failed to show an effect over placebo in the treatment of menopausal symptoms (77). A number of meta-analyses concluded that overall red clover was not clinically better than placebo for relief of vasomotor symptoms (70). In a trial involving 252 women, two red clover supplements were compared with placebo across 12 weeks (Promensil, containing 82 mg isoﬂavones, and Rimostil, containing 57 mg isoﬂavones) (78). Although Promensil did reduce hot ﬂashes more quickly than Rimostil or placebo, all three groups had the same reduction of hot ﬂashes at the end of 12 weeks. Another large trial of 205 women had similar results. While this does supply some evidence for a biological effect of Promensil, neither of the red clover supplements had a clinically significant effect when compared with placebo. Its effect on the endometrium must be further delineated.
Red clover has no clear demonstrable effect, it is believed to be estrogenic, and its effect on the breast and endometrium is not adequately studied. Coumarins are present in some clover species.
Dong quai (Angelica sinensis) has a long history of traditional use in menopause and in the treatment of menstrual problems. Traditionally, in the oriental system of medicine, it is used in combination with other botanicals. Several studies of the effectiveness of dong quai in treating the symptoms of menopause failed to show its effectiveness (79). No evidence exists to support the use of dong quai as a single agent in the treatment of menopausal symptoms. The use of dong quai in combination with other herbs, as is done traditionally, is not well studied. It is important to note that dong quai contains coumarin derivatives.
Kava (Piper methysticum) is native to the South Pacific, and one of its traditional uses is to reduce anxiety. It is often recommended for menopausal symptoms, particularly irritability, insomnia, and anxiety. Studies showed that 100 to 200 mg, three times daily, standardized to 30% kavalactones, decreases irritability and insomnia associated with menopause. It often is used in combination with other components, such as black cohosh and valerian, for the management of menopausal symptoms. One study that examined the use of kava in addition to hormone therapy for the treatment of anxiety showed that the combined use resulted in a significant decrease in anxiety when compared with hormone therapy alone (80).