Effects of lasofoxifene on the uterus, vagina, and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis).
OBJECTIVE
The purpose of this study was to assess the effects of lasofoxifene on the reproductive system in ovariectomized nonhuman primates.


METHODS
This was a 2-year, randomized study. Adult female macaques (Macaca fascicularis) were assigned randomly into 5 groups: ovariectomized, placebo-treated controls (n = 22); sham-ovariectomized, placebo-treated controls (n = 24); ovariectomized animals given 0.021 mg Premarin kg/d (conjugated equine estrogen; n = 25); lasofoxifene at 1.0 mg/kg/d (n = 23); or lasofoxifene at 5.0 mg/kg/d (n = 25). Outcomes included organ weights and histopathologic findings.


RESULTS
Lasofoxifene did not increase uterine weight or endometrial thickness and did not change mammary, vaginal, or cervical histologic condition. Mild endometrial fibrosis and cystic change were seen in lasofoxifene-treated animals, in contrast to significant uterine weight increases and endometrial hyperplasia induced by conjugated equine estrogen.


CONCLUSIONS
Lasofoxifene did not increase uterine weight and produced minor histologic uterine changes at the doses that were given and had no effect on the breast, vagina, or cervix.
Cline
J Mark
JM
Department of Pathology, Comparative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157-1040, USA. jmcline@wfubmc.edu
Botts
Suzanne
S
Lees
Cynthia J
CJ
Brommage
Robert
R
D000818:Animals; D001940:Breast / Q000187:drug effects*; D002584:Cervix Uteri / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005355:Fibrosis; D008252:Macaca fascicularis; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011759:Pyrrolidines / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects*
D011759:Pyrrolidines; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene