The purpose of this article was to review, with special attention to the hypothesized mechanisms of atherosclerosis and thrombosis, the literature on the association of estrogens and progestins with cardiovascular disease. The data sources included recent reviews and their citations as well as literature searches of Medline. For coronary heart disease, we relied on a recent meta-analysis; for the lipid effects of estrogens and progestins, we refer to recent reviews and studies; for stroke, we identified all cohort and case-control studies; and for the effects of hormones on coagulation factors, we identified all relevant studies. The lipid effects of estrogens in postmenopausal women probably prevent atherosclerosis, and we would expect long duration of use rather than current use to provide the greatest benefit. Few epidemiologic studies have, however, assessed duration of estrogen use. High doses of estrogens are likely to be thrombogenic during current use, and it is possible that even moderate doses may increase the risk of clotting among women who smoke or who have existing coronary atherosclerosis. Compared with the lipid effects of estrogens alone, the lipid effects of combined therapy with progestins may increase atherosclerosis. The effect of progestins on coagulation factors is largely unknown, and no epidemiologic study has assessed the risk of cardiovascular disease associated with the use of combined hormone therapy in postmenopausal women. Cardiovascular risk or benefit associated with the use of postmenopausal hormones may involve several competing mechanisms, including effects on prostaglandins and vascular tone as well as atherosclerosis and thrombosis.
(Arch Intern Med. 1993;153:1421-1427)