Black cohosh relieves menopausal symptoms likely by mimicking neurostransmitters: dopaminergic, noradrenergic, serotoninergic and GABAergic effects have been demonstrated (49).
Black cohosh may have estrogenic effects, but data are conflicting (23). Studies also show that it has no effect on LH, FSH, prolactin, or estradiol (24). A black cohosh extract was shown to have antiproliferative and antiestrogenic effects in ER-negative cells. This suggests that black cohosh mediates its effects via an estrogen-independent pathway (25), possibly through HER-2 signaling (26).
Black cohosh also has been investigated for anticancer potential. In an invitro study, it repressed the expression of cyclin D1 and ID3, and inhibited proliferation of HepG2, p53 positive, liver cells (43).
In prostate cancer cells, a black cohosh extract demonstrated antiproliferative effects, via impaired equilibrative nucleoside transporter (ENT) activity, resulting in hindered nucleoside uptake (50).
Hepatotoxicity is a major concern with black cohosh use. Evaluation of liver biopsies from two patients who took black cohosh supplements showed the pattern of pathological injury of liver cells to be identical to toxic necrosis, seen during autoimmune hepatitis (51).