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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1844-1854.)
© 1998 American Heart Association, Inc.

Original Contributions

Tibolone Prevents Atherosclerotic Lesion Formation in Cholesterol-Fed, Ovariectomized Rabbits

Pieter Zandberg; Jan L. M. Peters; Pierre N. M. Demacker; Martin J. Smit; Ernst G. de Reeder; Dirk G. Meuleman

From the Department of Vascular Pharmacology, Scientific Development Group, NV Organon, Oss (P.Z., J.L.M.P., M.J.S., E.G.d.R., D.G.M.), and the Department of Medicine, Division of General Internal Medicine, University Hospital, Nijmegen (P.N.M.D.), The Netherlands.

Correspondence to Pieter Zandberg, PhD, Department of Vascular Pharmacology, NV Organon, PO Box 20, 5340 BH Oss, Netherlands. E-mail P.Zandberg{at}organon.akzonobel.nl

Abstract—Tibolone (Org OD14), a synthetic steroid with estrogenic and progestogenic/androgenic properties, is clinically effective for the treatment of climacteric symptoms and the prevention and treatment of osteoporosis in postmenopausal women. The effect on atherogenesis, however, is not known. In the current study, we investigated the effect of tibolone in comparison with that of estradiol and norethisterone acetate on atherogenesis in 140 ovariectomized New Zealand White rabbits that had been induced by an atherogenic diet (0.4% cholesterol, 20 weeks). Tibolone at 18, 6, or 2 mg/d orally completely prevented cholesterol accumulation and fatty streak formation in the aorta; the impairment of endothelium-dependent smooth muscle relaxation of the aorta; and complex lesion formation after endothelial denudation in the carotid artery. Tibolone also reduced the increased postovariectomy plasma lipid concentrations. Analysis of the results, however, indicated that a substantial part of the strong, beneficial effects were plasma lipid independent. Compared with subcutaneous estradiol decanoate (150 µg once weekly) and oral 17ß-estradiol (4 mg/d), the effects of tibolone were more pronounced at equipotent uterotropic activity. Norethisterone acetate (1 mg/d) did not affect atherosclerotic lesion formation. There are no indications that the progestogenic/androgenic properties of tibolone counteracted its atheroprotective effect on the vessel wall. Therefore, tibolone has the intrinsic potential to be a compound that protects the arterial vessel wall against atherosclerotic processes.

Key Words: lipids • aorta • sex hormones • Org OD14 • atherogenesis

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