Transdermal estrogens do not appear to modify the extent of lesional areasof aortic atherosclerosis in oophorectomized rabbits on a cholesterol-richdiet

Cardiovascular disease (CVD) is the leading cause of death in older women i n industrialised countries. II has been suggested that it is the cessation of estrogen production by the ovaries that puts postmenopausal women at inc reased risk of CVD. Estrogen therapy has demonstrated a protective effect a gainst CVD and several reports suggest that diverse mechanisms may be invol ved. Oral estrogen appears to be associated with a better lipid profile tha n the use of transdermal estrogens; however, it is assumed that estrogens, oral and non-oral, have direct actions on the blood vessels that may exert an important role in cardiovascular disease prevention. To investigate the effect of transdermal estrogen therapy on aorta atherogenesis, we studied 2 0 cholesterol-fed New Zealand White rabbits for 4 months. The rabbits were oophorectomized and randomly assigned to two groups. Ten rabbits underwent bilateral ovariectomy followed by treatment with transdermal 17-beta-estrad iol (group E) and the other 10 received placebo after sterilization (Group C). After diet total levels of cholesterol increase in group C from 50.0 +/ - 12.5 to 820.9 +/- 186.0 mg/dl, and in group E from 52.6 +/- 9.4 to 811.4 +/- 213.0 mg/dl (no significant differences were observed between groups). Estrogen therapy increased twofold the total reactive antioxidant potential (TRAP group C: 22.5 +/- 16.7 mmol of Trolox/l vs. TRAP group E: 43.3 +/- 2 2.4 mmol of Trolox/l; P < 0.04). At 4 months, the cholesterol-rich diet cau sed atherosclerotic lesions in both treated and untreated rabbits affecting 18.7 +/- 14.5 and 21.6 +/- 9.7% of the aortic surface respectively. In sum mary, the principal result from this study was that although treatment with transdermal 17-beta-estradiol in cholesterol-fed ovariectomized rabbits in creases the TRAP to pre-surgery values: it does not inhibit aortic choleste rol accumulation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.