Premenopausal women are relatively protected against coronary heart disease (CHD) compared with men, but lose this advantage after surgical or natural menopause. Consequently, estrogens are believed to confer significant protection against coronary artery atherosclerosis (CAA). In addition, epidemiological studies have shown lower rates of CHD in postmenopausal users of estrogen replacement therapy than in women not taking hormone therapy. The cynomolgus monkey model (Macaca fascicularis) has proved valuable for gaining a better understanding of the effects of estrogen on coronary artery function and CAA. We have found that premenopausal cynomolgus monkeys have less CAA than male monkeys and surgically postmenopausal female monkeys, and that the hyperestrogenic state of pregnancy further inhibits CAA progression. Ovarian-deficient stressed females had more extensive CAA and impaired vascular function compared with unstressed monkeys, and estrogen-treated females (premenopausal or postmenopausal) had less CAA than untreated monkeys. The treatment effect in this model appears to be partially mediated by a decrease in low density lipoprotein uptake and/or degradation, and an improvement in coronary artery vascular function.
