Effects of hormone replacement therapy on atherosclerosis

The theme for this dissertation is hormone replacement therapy (HRT) and atherosclerosis. The following questions are addressed: (1) Does HRT have an effect on atherosclerosis? (2) Is there a difference in the effect of estrogen-only replacement therapy (ERT) compared to progestin + estrogen replacement therapy (PERT) on atherosclerosis? (3) Is carotid artery intima media thickness (IMT) measured in HRT treated nonhuman primates, correlated with carotid and coronary artery intimal area (i.e. plaque area)?; These questions were addressed in two studies. The first study in nonhuman primates compared carotid and coronary artery atherosclerosis in surgically-postmenopausal monkeys treated with ERT, PERT, or untreated. The second, an observational population-based study, compared carotid IMT in women who used ERT, PERT, or never used HRT. The results are: (1) Compared to the Control group, ERT inhibited atherosclerosis in coronary arteries (↓77%, p = 0.006) and carotid arteries (↓62%, p = 0.03) and PERT had nonsignificant effects (coronary: ↓46%, p = 0.21; carotid: ↓18%, p = 0.64) in nonhuman primates. In women carotid IMT was smaller in HRT users compared to never users (PERT: ↓2.8%, p = 0.03, ERT: ↓1.5%, p = 0.07) after adjustment for potential confounding variables. (2) There is probably no appreciable difference in atherosclerosis extent between ERT users and PERT users. In the experiment in nonhuman primates, the PERT group trended toward larger lesions relative to the ERT group and IMT was significantly larger in the PERT group. In the observational study in women, ERT users had slightly larger IMT than PERT users; but the differences were not significant in any of the analyses. (3) Atherosclerosis, as measured by carotid artery IMT, was correlated with plaque area in carotid arteries (r = 0.89, p < 0.0001) and coronary arteries (r = 0.72, p < 0.0001) in HRT treated nonhuman primates.; Among women with prevalent cardiovascular disease (CVD), HRT users had smaller IMT than never users and the magnitude of the difference appeared to be at least as large as for those without CVD. There was a trend toward smaller IMT with longer duration of estrogen use. While HRT appears to be atheroprotective, it is important to determine whether HRT has an effect on CVD morbidity and mortality.