The epidemiologic evidence, even on repeated examination, is very consistent in showing a beneficial effect. For example, in one study conducted in oophorectomized cynomolgus monkeys with atherosclerosis, administration of estrogen diminished areas of arterial plaque to nearly normal levels. Administration of MPA with estrogen appeared to reverse this benefit, while administration of MPA alone resulted in the development of additional atherosclerotic plaque over baseline. 13 Other laboratory studies suggest that alternative progestins may offer a more favorable cardiovascular effect. Thus, far from negating estrogen's beneficial effect, NA actually accentuated it.
Additional studies are currently under way in the primate model.
In order to examine the effects of estrogen and MPA on vascular reactivity, Gerhard and colleagues conducted a study in postmenopausal women in which a brachial artery flow-mediated vasodilation protocol was used as a surrogate for angiographic evaluation. Administration of placebo produced minimal and inadequate vasodilation. By contrast, both estrogen alone and estrogen plus micronized progesterone produced additional vasodilation. In a separate study using MPA as the progestin, the administration of MPA in addition to estrogen had the effect of converting a vasodilatory response to a vasoconstrictive response. 16 Human studies have provided additional evidence of a beneficial cardiovascular effect of NA, at least on lipoproteins.