Contrasting effects of two hormone replacement therapies on the cardiovascular and mammary gland outcomes in surgically postmenopausal monkeys

OBJECTIVE: The purpose of this study was to compare the effects of two hormone replacement therapies on the intermediate end points of coronary heart disease and mammary gland hyperplasia in postmenopausal monkeys. STUDY DESIGN: Surgically postmenopausal cynomolgus monkeys were fed an atherogenic diet for 12 months while receiving no treatment (control, n = 19), conjugated equine estrogens plus continuous medroxyprogesterone acetate (n = 19), or ethinyl estradiol plus norethindrone acetate (n = 21) at doses that were scaled from those doses taken by women. RESULTS: Quantitative coronary angiography revealed that the arteries of the control group and the conjugated equine estrogens plus continuous medroxyprogesterone acetate-treated animals constricted in response to acetylcholine (-5.4% 1.4% and -6.2% 1.5%, respectively), whereas those arteries in the animals in the ethinyl estradiol plus norethindrone acetate group did not (P = .002). The incidence of dobutamine-induced ST-segment depression in the ethinyl estradiol plus norethindrone acetate group (10.5%) was significantly less than in the control group (68.8%, P = .001) or the conjugated equine estrogens plus continuous medroxyprogesterone acetate group (50%, P = .01). Conjugated equine estrogens plus continuous medroxyprogesterone acetate, but not ethinyl estradiol plus norethindrone acetate, induced diffuse epithelial tissue proliferation in the mammary glands (P = .0006). CONCLUSION: Ethinyl estradiol plus norethindrone acetate protected, against atherosclerosis-induced endothelium-mediated vasoconstriction of coronary arteries and heart rate-induced myocardial ischemia and did not induce epithelial tissue proliferation (tissue density) in the mammary gland.