ABSTRACT
Early experimental models of estrogen-deficient animals with coronary artery atherosclerosis used chickens and pigeons. However, nonhuman primate models replaced these earlier models because of greater similarities to human beings. Our studies have focused on female cynomolgus macaques, especially surgically post-menopausal (i.e., estrogen-deficient) animals fed an atherogenic diet. We found that male and ovariectomized female cynomolgus macaques did not differ with respect to coronary artery atherosclerosis, while premenopausal females had half the coronary artery atherosclerosis of their ovariectomized counterparts. In two studies of hormone replacement therapy of ovariectomized cynomolgus macaques, we discovered that estrogen replacement therapy (either parenteral estradiol or oral conjugated equine estrogens) resulted in 50-70% reductions in the extent of coronary artery atherosclerosis compared to control animals. However, while continuous estradiol/ sequential progesterone replacement, administered parenterally, caused a 50% reduction in atherosclerosis extent, continuous conjugated equine estrogens and MPA given orally resulted in atherosclerosis extent that did not differ from untreated controls. These results indicate that effects of progestin coadministered with estrogen on coronary arteries may depend on type, dose, route of administration or pattern (continuous versus sequential) of administration. Furthermore, some forms of progestin cotherapy may antagonize favorable effects of estrogen.
