Sex hormone replacement
therapy provides several advantages in the quality of life for climacteric women. However,
estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of
cancer development in these organs. The lower incidence of
mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy
isoflavones, including
genistein. We have previously shown that
genistein induces an
estradiol-like
hypertrophy of uterine cells, but does not induce cell proliferation, uterine
eosinophilia, or endometrial
edema. It also inhibits
estradiol-induced mitosis in uterine cells and
hormone-induced uterine
eosinophilia and endometrial
edema. Nevertheless,
genistein stimulates growth of human
breast cancer cells in culture; therefore, it is not an ideal
estrogen for use in
hormone replacement therapy (HRD). The present study investigated the effect of another soy
isoflavone,
daidzein (subcutaneous, 0.066 mg/kg
body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17β (E(2); subcutaneous, 0.33 mg/kg
body weight). In addition, we investigated the effects of
daidzein (1 μg/mL) or E(2) on the growth of human
breast cancer cells in culture. Results indicate that
daidzein stimulates growth of
breast cancer cells and potentiates
estrogen-induced cell proliferation in the uterus. We suggest caution for the use of
daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new
phytoestrogens that selectively inhibit cell proliferation in the uterus and breast.