Oral Contraceptives and Hormone Replacement Therapy Do Not Increase the Incidence of Arterial Thrombosis in a Nonhuman Primate Model

From the Center for Thrombosis and Hemostasis, Department of Pathology and Laboratory Medicine, and the Division of Laboratory Animal Medicine, School of Medicine, University of North Carolina at Chapel Hill (D.A.B., D.E.B.); and Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (J.K.W., M.R.A., E.K.H.).

Correspondence to Dr Dwight A. Bellinger, The School of Medicine, Division of Laboratory Animal Medicine, The University of North Carolina at Chapel Hill, CB#7115, B12 Berryhill Hall, Chapel Hill, NC 27599-7115. E-mail dbsbsb{at}med.unc.edu

Abstract—Older oral contraceptive (OC) formulations containing high doses of potent synthetic estrogens and progestins are associated with increased risk of thrombosis. To examine the effects of current low-dose OC and hormone replacement therapy (HRT) regimens on arterial thrombosis, premenopausal and surgically postmenopausal cynomolgus monkeys were divided into four treatment groups. Premenopausal monkeys were given either no OCs or ethinyl estradiol and levonorgestrel as an OC at a dose equivalent to that currently given to women. Postmenopausal monkeys were given either no HRT or conjugated equine estrogens and medroxyprogesterone as an HRT at a dose equivalent to that currently given to women. The monkeys were fed an atherogenic diet containing these treatments for 27 to 30 months. At the end of this time, arterial thrombosis was evaluated with a standardized stenosis/injury procedure in the left carotid artery. Blood flow velocity was monitored for cyclic or permanent occlusive thrombosis. The current OC and HRT regimens did not increase the susceptibility of the artery wall to develop an occlusive thrombus following injury and stenosis. In fact, there was a reduction in the incidence of thrombosis in the OC animals compared with untreated controls. Increased amounts of atherosclerosis were associated with an increased incidence of occlusive arterial thrombosis. Several selected coagulation parameters [von Willebrand factor, protein C, lipoprotein(a), and platelet aggregation] did not appear to be associated with either the amount of atherosclerosis or incidence of arterial thrombosis.

Key Words: oral contraceptives • hormone replacement therapy • arterial thrombosis • atherosclerosis • cynomolgus monkeys

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