Phytoestrogen including soybean isoflavones has structural similarity to es
trogen and exhibits beneficial effects on bone tissue to protect against bo
ne loss under estrogen-deficient conditions. Recent studies also indicate a
possible action of isoflavones as endocrine disrupters in reproductive tis
sues. In this study, we administered various dosages of genistein to ovarie
ctomized (OVX) mice, and compared the effective dosages of genistein on bon
e and uterus. Treatment with genistein at 0.7 mg/day prevented trabecular b
one loss in OVX mice without hypertrophic effects on the uterus, while admi
nistration of 5 mg/day of genistein induced uterine hypertrophy. The serum
levels of genistein in OVX mice treated with 0.7 mg/day and 5 mg/day were 3
-fold (1.3 nmol/ml) and 50-fold (20.4 nmol/ml) higher than that in OVX mice
. These results suggest that there is a marked difference between genistein
dosages that protect against bone loss and those that induce uterine hyper
trophy. (C) 2000 Academic Press.