The new conundrum: do estrogens have any cardiovascular benefits?

Clearly, a new era has begun, with increasing numbers of the scientific/medical community asking whether estrogens have any cardiovascular benefits. Doubts have arisen from two randomized prospective trials. The Heart and Estrogen/progestin Replacement Study (women who were generally beyond 65 years of age with preexisting coronary heart disease) found no benefit in reducing coronary events by a combination of estrogens and a progestin. Later, the Estrogen Replacement Atherosclerosis Trial reported that no benefit could be shown for either conjugated equine estrogens only or the combined therapy group for women with preexisting coronary artery stenosis. There are lessons to be taken from monkey models about the new conundrum. Estrogens have beneficial effects in the early stages of atherogenesis, but have little or no beneficial effects in the final stages of plaque complications, instability and coronary heart disease events. Using the monkey model, we have addressed the question of when "primary prevention" should begin. We examined the effect of contraceptive steroid treatment of stressed animals at high risk to progressing atherosclerosis due to their estrogen deficiency and subsequently examined the effect of estrogen replacement therapy or no estrogen replacement therapy following surgical menopause. The most robust inhibition of atherosclerosis progression was found in those animals given contraceptive steroids premenopausally and subsequently estrogen replacement postmenopausally. The notion of starting contraceptive therapy during the perimenopausal period to be followed immediately with estrogen replacement postmenopausally is likely to be the most favorable approach to the inhibition of atherosclerosis progression.