The estrogenic properties of natural and synthetic isoflavones in the ovariectomized hamster

Coronary heart disease (CHD) is the leading cause of death for postmenopausal women. This increased risk for CHD has been attributed in part to alterations in lipid metabolism and body fat distribution associated with estrogen deficiency. Since the hamster exhibits similarities to humans in terms of cholesterol metabolism, the effects of ovariectomy on the female hamster were examined. Twenty-one 65-day old female Golden Syrian hamsters were ovariectomized or sham-operated and fed a chow diet for 65 days. Ovariectomy increased ( p < 0.05) total and high density lipoprotein (HDL) cholesterol as well as abdominal fat levels (p < 0.001), despite equal food intake. Abdominal fat increases are consistent with human menopause; however, the observed increases in HDL cholesterol preclude the use of the ovariectomized hamster as an ideal model for human menopause in terms of lipoprotein metabolism and CHD risk.; Data suggest that the attenuation of postmenopausal symptoms with soy consumption is related to the estrogenic activity of soy isoflavones. The tissue-specific effects of soy isoflavones in the ovariectomized hamster were examined to determine if these effects paralleled those of estrogen. Seventy-five 65-d old female Golden Syrian hamsters were ovariectomized (ovx) or sham operated (sham) and divided into 5 groups [(1) sham; (2) ovx; (3) ovx+17β-estradiol (E₂); (4) ovx+ipriflavone (IP); (5) ovx+isoflavones (ISO)]. ISO received a soy diet with normal isoflavone levels (2.3 mg isoflavones/g protein); the other groups received an isoflavone-deficient soy diet (0.1–0.3 mg isoflavones/g protein). Groups were pair fed for 65 days, then exsanguinated. Ovx reduced uterine weight by 70% relative to sham (p < 0.0001). Estrogen, but not isoflavone treatment prevented uterine atrophy. Total and HDL cholesterol levels were similar among treatment groups. Compared to sham, ovx increased abdominal fat by 58% (p < 0.0001); such increases were prevented in E₂ and ISO. Serum leptin per gram of abdominal fat was higher (p < 0.01) in ISO in comparison to ovx. Relative to ovx, only E₂ increased indicators of cholesterologenesis and cholesterol excretion. Isoflavones (1) are most likely not responsible for the hypocholesterolemic effects of soy; (2) attenuate abdominal fat gains associated with ovariectomy; and (3) appear to exert estrogenic effects in a tissue specific manner.