Effects of estrogen and estrogenic compounds on cognition in ovariectomized rats.

To evaluate the effects of estrogen and estrogenic compounds on cognition in ovariectomized rats. Female Sprague-Dawley rats (3-5 months old) weighing 250-300 g were randomly divided into seven groups: Sham, ovariectomized (OVX), OVX plus estradiol valerate, OVX plus ipriflavone, OVX plus raloxifene, OVX plus tibolone, OVX plus low-dose estradiol valerate and ipriflavone. All treatments were given orally for 3 months; whereas the drug groups received indicated drugs, the Sham and OVX control groups received saline. The escape latency of rats was tested by the Morris water maze test and the expression of amyloid precursor protein (APP) in hippocampus was determined by reverse transcription polymerase chain reaction. The level of serum estradiol and the diameter of the endometrial gland and the thickness of endometrium were also evaluated. The latency of the OVX group was noticeably longer than that of the Sham group, and the latency of all treatment groups was lower than that of OVX rats. The expression of APP mRNA in the hippocampii of OVX rats was significantly increased relative to that in Sham rats; interestingly, expression of APP in treatment groups was significantly reduced relative to OVX rats. Our data indicate that estrogenic compounds can antagonize cognitive impairment and that all these compounds cause only mild stimulation on the endometrium compared to estrogen. Inhibition of APP expression in the hippocampus may account for, at least partially, the protective effects of these estrogenic compounds against cognitive defects. Our data suggest that estrogenic compounds (raloxifene, tibolone and ipriflavone) may be a promising approach to antagonize cognitive impairment in postmenopausal women.