Effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys

Menopause. 2014 Jan;21(1):8-14. doi: 10.1097/GME.0b013e31829370e5.


Objective: This study aims to evaluate the effects of a new selective estrogen receptor modulator (bazedoxifene acetate [BZA]) and a tissue-specific estrogen complex (BZA combined with conjugated equine estrogens [CEE]) on the extent and severity of cerebral artery atherosclerosis.

Methods: Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. After an experimental period of 20 months (approximately equivalent to 5 years of participant experience), the extent and severity of atherosclerosis in the common carotid artery, carotid bifurcation, internal carotid artery, and basilar artery were determined. Lesion severity was determined using the American Heart Association grading system (grades 0-V).

Results: BZA had no consistent adverse effects on the extent and severity of atherosclerosis in the cerebral arteries and did not attenuate the beneficial effects of CEE on the severity of common carotid artery atherosclerosis. Although CEE had only modest beneficial effects on the extent of carotid bifurcation atherosclerosis, the severity of lesions and the number of affected cases in the common carotid artery were reduced with CEE treatment. As reported previously, plasma lipid profiles did not differ among the treatment groups.

Conclusions: In this long-term (equivalent to 5 human patient-years) nonhuman primate trial, BZA shows no consistent adverse effect on cerebral artery atherosclerosis and does not attenuate the modest beneficial effect of CEE on the common carotid artery. Furthermore, CEE inhibits the development of complicated plaques in the common carotid artery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basilar Artery / pathology
  • Carotid Artery Diseases / pathology*
  • Carotid Artery Diseases / prevention & control
  • Carotid Artery, Internal / pathology
  • Diet, Atherogenic
  • Drug Combinations
  • Estrogens / therapeutic use*
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Haplorhini
  • Indoles / therapeutic use*
  • Intracranial Arteriosclerosis / pathology*
  • Intracranial Arteriosclerosis / prevention & control
  • Menopause / drug effects
  • Random Allocation
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Severity of Illness Index


  • Drug Combinations
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Indoles
  • Selective Estrogen Receptor Modulators
  • bazedoxifene