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.

Study Design: 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.

Conclusion: 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.