Effects of lasofoxifene on the uterus, vagina, and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis)

Am J Obstet Gynecol. 2008 Aug;199(2):158.e1-8. doi: 10.1016/j.ajog.2008.02.020. Epub 2008 May 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast / drug effects*
  • Cervix Uteri / drug effects
  • Endometrium / drug effects
  • Endometrium / pathology
  • Female
  • Fibrosis
  • Macaca fascicularis
  • Organ Size / drug effects
  • Ovariectomy
  • Pyrrolidines / pharmacology*
  • Tetrahydronaphthalenes / pharmacology*
  • Uterus / drug effects*
  • Vagina / drug effects*

Substances

  • Pyrrolidines
  • Tetrahydronaphthalenes
  • Lasofoxifene