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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

Clarkson, Thomas B. DVM1; Ethun, Kelly F. DVM, PhD1; Pajewski, Nicholas M. PhD2; Golden, Debbie BS1; Floyd, Edison BS1; Appt, Susan E. DVM1

doi: 10.1097/GME.0b013e31829370e5
Original Articles

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.

From the Departments of 1Pathology/Comparative Medicine and 2Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.

Received February 12, 2013; revised and accepted March 20, 2013.

Funding/support: This work was supported by Pfizer Inc. (an investigator-originated grant to T.B.C.) and the National Institutes of Health Office of the Director (grant 8T32OD010957 to K.F.E.) and in part by the National Institute on Aging (award number R01AG027847 to S.E.A.).

Financial disclosure/conflicts of interest: T.B.C. received an investigator-originated grant from Pfizer and an investigator-originated grant from Merck.

Address correspondence to: Thomas B. Clarkson, DVM, Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail:

© 2014 by The North American Menopause Society.