The aim of the present study was to investigate whether there are gender-specific differences in the effects of testosterone and estrogen on the process of atherogenesis. Thirty-two castrated male and 32 ovariectomized female rabbits were separated into 4 study groups of 8 males and 8 females each and received postoperatively a 0.5% cholesterol diet 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 estrogen combined with testosterone in above dosages were administered. Computerized morphometric analysis of the intimal thickening in the proximal aortic arch showed a significant inhibitory effect of estrogen in female and of testosterone in male animals (P < .05). In the group with combined treatment, the plaque size in both sexes was smaller than in the animals of the control group (P < .05). These differences were independent of changes in plasma lipid parameters. The incorporation of 5'-bromo-2'-deoxyuridine, associated with cell proliferation, into cells of the neointima was not significantly affected by the different hormone application regimens in males. In females, the incorporation rate was significantly lowered in the estrogen treated group compared with the control group (P < .05). Due to the observed differences in the sex specific atheroprotective effects of testosterone and estrogen, these data suggest that complex hormone interactions, which are independent of changes in plasma lipids, may play an important role in the process of atherogenesis.
ERT is associated with a reduced incidence of coronary risk and cardiac events in postmenopausal women, but increases the risk of endometrial hyperplasia and carcinoma. Combined estrogen and progestin therapy protects the endometrium; however, its effects on heart disease risk factors are not completely known. In our study, 56 ovariectomized New Zealand White rabbits in 7 groups received a 0.5% cholesterol diet for 12 weeks. Controls were not treated with hormones. All other animals received (per kilogram body weight per week) intramuscular injections of either 0.3 mg estrogen (estradiol valerate) alone, 8.3 mg progestin (hydroxyprogesterone caproate) alone, estrogen and progestin continuously in 3 different dosages (0.3 and 8.3 mg; 1 and 8.3 mg; or 1 and 2.8 mg; estrogen and progestin, respectively), or 1 mg estrogen with 25 mg progestin sequentially in 2-week cycles. Eight non-ovariectomized animals served as further controls for endometrial analysis. Morphometric analysis of plaque size in the aortic arch showed that estrogen monotherapy, and the 3 combined therapies with 1 mg estrogen, significantly reduced intimal thickening (P<0.05). The application of progestin alone had no effect on plaque size. The endometrium was enlarged by 3-fold after estrogen treatment, and was decreased by half after progestin treatment, compared with control uteri (P<0.05). In all groups with combined hormone regimens, endometrial size was not significantly different from control uteri. However, these uteri showed more inflammatory reactions, especially when higher doses of hormones were given. In this animal model, doses of progestin that are able to successfully reduce the proliferative effect of estrogen on endometrium do not diminish the desirable antiatherosclerotic properties of estrogen.
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