GENDER-SPECIFIC DIFFERENCES IN THE EFFECTS OF TESTOSTERONE AND ESTROGEN ON THE DEVELOPMENT OF ATHEROSCLEROSIS IN RABBITS

The aim of the present study was to investigate whether there are gend er-specific differences in the effects of testosterone and estrogen on the process of atherogenesis. Thirty-two castrated male and 32 ovarie ctomized female rabbits were separated into 4 study groups of 8 males and 8 females each and received postoperatively a 0.5% cholesterol die t for 12 weeks. During this period either no hormones, estradiol (1 mg /kg body wt/week), testosterone (25 mg/kg body wt/week IMM), or estrog en combined with testosterone in above dosages were administered. Comp uterized morphometric analysis of the intimal thickening in the proxim al aortic arch showed a significant inhibitory effect of estrogen in f emale and of testosterone in male animals (P<.05). In the group with c ombined treatment, the plaque size in both sexes was smaller than in t he animals of the control group (P<.05). These differences were indepe ndent of changes in plasma lipid parameters. The incorporation of 5'-b romo-2'-deoxyuridine, associated with cell proliferation, into cells o f the neointima was not significantly affected by the different hormon e application regimens in males. In females, the incorporation rate wa s significantly lowered in the estrogen treated group compared with th e control group (P<.05). Due to the observed differences in the sex sp ecific atheroprotective effects of testosterone and estrogen, these da ta suggest that complex hormone interactions, which are independent of changes in plasma lipids, may play an important role in the process o f atherogenesis.