Estrogen replacement therapy is commonly used to replace the loss of estrogen in post-menopausal women. However, it is not suitable to be used in women taking tamoxifen as both of the drugs increase the risk of endometrial cancer. This project aimed to study the potential of using the natural compound glabridin in combination with tamoxifen as a drug for estrogen replacement therapy. Ishikawa and MCF-7 cells were used to investigate the estrogenic activities stimulated by the combination of tamoxifen and glabridin through ALP and MTT assays. The expressions of the ESR1 and bcl-2 genes have also been determined using RT-PCR. The results indicated that the combination of 1 x 10(-5)M tamoxifen and 1 x 10(-6)M glabridin exhibited estrogenic activities and suppressed cell growth in both cell lines. The relative expressions of ESR1 and bcl-2 genes indicated that the estrogenicity expressed by the combinatory drug was regulated by estrogen receptor a; however, the reduction in cell proliferation was not modulated by bcl-2 anti-apoptotic proteins. These results suggested that the combination of tamoxifen and glabridin has potential to be used as an estrogen replacement drug with a reduced risk of endometrial cancer that has arisen from the intake of tamoxifen.