Aortic plaque size and endometrial response in cholesterol-fed rabbits treated with estrogen plus continuous or sequential progestin

ERT is associated with a reduced incidence of coronary risk and cardiac eve nts in postmenopausal women, but increases the risk of endometrial hyperpla sia and carcinoma. Combined estrogen and progestin therapy protects the end ometrium; however, its effects on heart disease risk factors are not comple tely 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 tre ated with hormones. All other animals received (per kilogram body weight pe r week) intramuscular injections of either 0.3 mg estrogen(estradiol valera te) 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 I and 2.8 mg; estrogen and progestin, respectively), or 1 mg estro gen with 25 mg progestin sequentially in 2-week cycles. Eight non-ovariecto mized animals served as further controls for endometrial analysis. Morphome tric analysis of plaque size in the aortic arch showed that estrogen monoth erapy, and the 3 combined therapies with 1 mg estrogen, significantly reduc ed intimal thickening (P<0.05). The application of progestin alone had no e ffect on plaque size. The endometrium was enlarged by 3-fold after estrogen treatment, and was decreased by half after progestin treatment, compared w ith control uteri (P<0.05). In all groups with combined hormone regimens, e ndometrial size was not significantly different from control uteri. However , these uteri showed more inflammatory reactions, especially when higher do ses of hormones were given, rn this animal model, doses of progestin that a re able to successfully reduce the proliferative effect of estrogen on endo metrium do not diminish the desirable antiatherosclerotic properties of est rogen.