DIFFERENT EFFECTS OF ESTROGEN AND PROGESTERONE ON EXPERIMENTAL ATHEROSCLEROSIS IN FEMALE VERSUS MALE RABBITS - QUANTIFICATION OF CELLULAR PROLIFERATION BY BROMODEOXYURIDINE

Background The aim of the present study was to compare the effect of e strogen and progesterone on the development of experimental atheroscle rosis in female versus male rabbits to assess possible sex-specific di fferences. Methods and Results A total of 32 female and 32 male New Ze aland White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week)) or combined estradiol-progesterone in these dosages during 12 weeks. Ovar iectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyu ridine labeling was performed to determine the extent of cellular prol iferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of es trogen on intimal plaque size was found in female rabbits compared wit h the ovariectomized control group (0.7+/-0.5 versus 3.7+/-2.5 mm(2), P<.002; proliferating cells, 3.1+/-1.8% versus 8.5+/-2.6%, P<.002). In combination with progesterone, however, estrogen was not able to redu ce intimal plaque size or cellular proliferation. In contrast, estradi ol in castrated male rabbits was not associated with an inhibitory eff ect on cellular proliferation or intimal thickening compared with cont rols (estrogen treatment, 7.6+/-2.1% proliferating cells and 2.8+/-1.0 mm(2) neointima; control group, 7.2+/-2.1% cellular proliferation and 2.9+/-1.2 mm(2) intimal thickening). Conclusions Our data suggest tha t the atheroprotective effect of estrogen is probably due to a mechani sm that is present in female rabbits only.