Effects of two novel selective estrogen receptor modulators, raloxifene, tamoxifen, and ethinyl estradiol on the uterus, vagina and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis).
Assess effects of 2 novel selective estrogen receptor modulators on the reproductive system. Adult, ovariectomized, female Macaca fascicularis, n = 3 per group, orally dosed for 12 weeks with vehicle; selective estrogen receptor modulator 393 (2, 4, or 8 mg/kg/day); selective estrogen receptor modulator 379 (4 mg/kg per day); raloxifene (3 mg/kg per day); tamoxifen (1 mg/kg per day); or ethinyl estradiol (3 microg/kg per day). Outcomes included organ weights, histopathology, plasma lipids, and bone biomarkers. Novel selective estrogen receptor modulators tested did not alter uterine weight or endometrial histology. Tamoxifen and ethinyl estradiol increased uterine weight 2- to 3-fold (P <.05) and endometrial glandular proliferation 5- to 6-fold (P < .05). Adrenal weight was 50% higher in the tamoxifen group. Ethinyl estradiol increased breast lobular epithelial proliferation 6-fold (P < .05). Selective estrogen receptor modulators 393 and ethinyl estradiol decreased bone biomarkers. The results for raloxifene, tamoxifen, and ethinyl estradiol are consistent with previous findings, and results for selective estrogen receptor modulator 393 and selective estrogen receptor modulator 379 indicate potential for tissue selectivity.