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).
OBJECTIVE
Assess effects of 2 novel selective estrogen receptor modulators on the reproductive system.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sikoski
Paul
P
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Register
Thomas C
TC
Lees
Cynthia J
CJ
Lundeen
Scott
S
Hutchison
James
J
Brown
Kathryn H
KH
Cline
J Mark
JM
D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D014621:Vagina / Q000187:drug effects* / Q000473:pathology
D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D020849:Raloxifene Hydrochloride