Serum lipids and arterial plaque load are altered independently with high-dose progesterone in hypercholesterolemic male rabbits

Antiatherogenic effects of sex steroids in premenopausal women are not well defined. Therefore, we employed an established rabbit model for atheroscle rosis to study the effects of exogenous estrogen and a progesterone analogu e (P) on serum lipids and aortic plaque load. Serum cholesterol (C) and tri glyceride (T) levers and atherosclerotic plaque loads were compared in 5 gr oups of male New Zealand White rabbits fed a 12-week, C-rich diet: 1 contro l group (CG) and 4 groups treated with estriol (E), haloperidol (H), low-do se 17-hydroxyprogesterone (LDP), or high-dose 17-hydroxyprogesterone (HDP). Serum P was measured in the LDP and HDP groups. Serial histologic sections (15 each of 27 ascending aortas) were studied by light microscopy and comp uterized morphometric analysis. Plaque load is defined as the ratio of inti mal area to medial area (I/M). Exogenous E (p < 0.001), H (P = 0.02), LDP a nd HDP (P < 0.001, each) were found to be significantly associated with les s aortic plaque load than controls. In a multivariate analysis, after contr olling for the differences in serum C and T levels, HDP Co = 0.014) was fou nd to be associated with less aortic plaque load than controls, and this as sociation approached statistical significance in the E (p = 0.052) and H (p = 0.069) groups. These data suggest that the mechanism(s) involved with th e antiatherogenic effect of HDP in this animal model is, or are, independen t of an alteration in serum lipids. (C) 2000 by Elsevier Science Inc.