D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assay

D‐003 is a mixture of long‐chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D‐003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone‐replacement therapy, D‐003 displays cholesterol‐lowering and anti‐resorptive effects. We have studied its potential oestrogenic activity in‐vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham‐operated group and four groups of ovariectomized rats, one treated with vehicle, one with D‐003 (50 mg kg−1), one with oestradiol benzoate (30 μg kg−1) and one with D‐003 (50 mg kg−1) plus oestradiol benzoate (30 μg kg−1). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham‐operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D‐003. Concurrent administration of D‐003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D‐003 orally given at 50 mg kg−1, a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti‐oestrogenic activity in‐vivo, as assessed in the uterotrophic assay.