The literature suggests that orally-administered estrogen replacement has a beneficient influence on plasma lipids and lipoproteins (decreased LDL, increased HDL) while parenterally-administered estrogen has little or no effect; and that medroxyprogesterone acetate may have an additional beneficient influence. However, the influence of estrogen-progestogen replacement therapy on extent of atherosclerosis in postmenopausal females is unknown. One objective of this study is to assess the effects of postmenopausal hormone replacement on atherosclerosis risk factors: plasma lipids, apoproteins, lipoproteins, blood pressure, glucose tolerance, and certain behavioral and psychosocial factors. Additional objectives are to assess the effects of hormone replacement on: 1) postheparin lipase activities; 2) the binding capacity of sex hormone binding globulin, which is an indicator of the relative estrogenicity of the treatments; and 3) insulin and glucagon responses to an intravenous glucose challenge. The principal objective of this study is to assess the effects of two commonly-prescribed types of estrogen replacement, orally administered conjugated equine estrogens (Premarin) or parenterally-administered estradiol, alone or in combination with a frequently prescribed progestogen, medroxyprogesterone acetate (Provera) on extent of aortic, coronary, femoral, extra- and intracranial artery atherosclerosis in menopausal (ovariectomized) cynomolgus monkeys fed an atherogenic diet for three years. Atherosclerosis will be quantitated morphometrically at necropsy. The results of this study should provide valuable evidence regarding the influence of these two types of estrogen replacement alone or in combination with medroxyprogesterone acetate on extent of atherosclerosis. Additionally, evidence will be obtained regarding the role of plasm lipids and lipoproteins and other risk factors in mediating such an influence. Long term objectives are to determine mechanisms by which impairment or loss of ovarian function influence atherogenesis and its risk factors, and to determine what types and dosage levels of postmenopausal hormonal replacement are associated with optimal benefit and minimal risk.
