Estrogen therapies, lipids, and the heart disease prevention controversy

One of the most highly unexpected reports in recent medical literature was the lack of benefit of estrogen-progestin replacement therapy in cardiovascular disease prevention in postmenopausal women. The ensuing negative view of hormone replacement therapy has now extended to all forms of postmenopausal hormone treatment, including estrogen alone. Is this pessimism justified? A review of the effects of estrogens and progestins on the estrogen-sensitive systems of the body can help explain why combined oral estrogen and low-dose continuous medroxyprogesterone acetate administration may not be the paradigm for all other forms of postmenopausal hormone replacement. Some of these effects include the following: progestins are anti-estrogens, as evidenced in their divergent effects on plasma lipids; not all progestins are equal in their effect on lipids and other physiologic functions; administration of any hormone by mouth is not physiologic; giving estrogen 10 to 15 years postmenopausally may be too late to prevent atherosclerosis. On the other hand, high doses of oral estrogen/progestin in the presence of high cardiovascular risk appear to promote atherosclerosis risk. Given the current evidence the common sense answer to the question of the benefit of estrogen is “it depends.” Until these and other points are formally addressed, the hypothesis that estrogen prevents heart disease remains open.