Abstract
Kampo medicines are frequently administered to patients with multiple menopausal symptoms as an alternative to hormone replacement therapy (HRT). The level of estrogen-like activity in the medicines, however, had not been clarified. In order to assess the estrogen-like activity, we established a high-sensitivity luciferase reporter gene assay using MCF-7 cells. Twenty-five kinds of Kampo medicines used for the treatment of menopausal syndromes and gynecological diseases were subjected to the assay. All of them except for tokishakuyakusan (TJ-23) showed estrogen-like activity. The estrogen-like activity was corrected with a daily-dose of each of the Kampo medicines to evaluate the dose as β-estradiol (E2) per day. In kakkonto (TJ-1 and OMRC-K1) and kakkonkokato (OMRC-K2) the estrogen-like activities were detected at 1 to 3 μg/day and the activities in other Kampo medicines were under 150 ng/day. Thus, the levels of estrogen-like activities in these Kampo medicines turned out to be lower than the level of HRT (625 μg/day of estrogen). Furthermore, we examined the mechanism of action for kakkonto that showed the highest level of estrogen-like activity. The medicine as well as expressed estrogen-like activity through estrogen receptor and estrogen responsive element. These results indicated that almost all of the Kampo medicines used for patients with multiple menopausal symptoms have estrogen-like activities. However, it is a possibility that the clinical efficacies of the medicines are induced by a different mechanism from HRT, since Kampo medicines showed extremely low levels of estrogen-like activities. Therefore Kampo medicines may be safer than HRT. In order to guarantee the safety of routine and long-term administration of Kampo medicines, further investigations are required, for instance, detecting the blood estrogen level and the growth-promoting effect to hormone-dependent tumors.
