ESTROGENS, PROGESTINS, AND CORONARY-ARTERY REACTIVITY IN ATHEROSCLEROTIC MONKEYS

It has been known for many years that sex hormones modulate vasodilato r responses of arteries supplying the uterus with blood. Recently, it has been shown that sex hormones such as estrogen modulate vasomotor r esponses of other arteries, including coronary arteries. It is thought that modulation of vasodilator and constrictor responses of coronary arteries may be one mechanism by which estrogen affects the risk of co ronary heart disease. Although several studies have examined the effec ts (and potential mechanisms) of estrogen on vasodilator responses of nonatherosclerotic arteries, few have focused on estrogen's effects on atherosclerotic coronary arteries. In studies of ovariectomized ather osclerotic female cynomolgus monkeys, both long-term (2 years) and sho rtterm (20 min) estradiol treatment augments dilator responses to acet ylcholine, but not nitroglycerin. Presumably, this indicates an effect of estradiol on endothelium-mediated dilator responses of coronary ar teries. Addition of the progestin medroxyprogesterone acetate diminish es the beneficial effect of conjugated equine estrogens on these dilat or responses. This is significant because a progestin is usually added to estrogen replacement to reduce the risk of endometrial and breast cancer associated with unopposed estrogen therapy. However, it would s eem that not all progestins act similarly on vascular reactivity. Stud ies in monkeys indicate that addition of progesterone or the progestin medroxyprogesterone acetate does not diminish the beneficial effects of estrogen on coronary dilator responses. Thus it would appear that d ifferent estrogen/progestin combinations may affect vascular reactivit y in different manners, There is also an effort being made to examine the potential of different kinds of estrogens on cardiovascular risk. Studies in monkeys indicate that one of the estrogens found in conjuga ted equine estrogens (17 alpha-dihydroequilenin) has estrogen effects on vascular reactivity without having detrimental effects on uterine p athology. The isoflavones ''plant estrogens'' found in soy protein als o have estrogenic effects on vascular reactivity and inhibition. (C) 1 998 Published by Elsevier Science Ltd. All rights reserved.