Controversy of hormone treatment and cardiovascular function: need for strengthened collaborations between preclinical and clinical scientists.

Over the last five years, there have been several major randomized clinical trials assessing the use of hormone therapy as an adjunct treatment for primary and secondary prevention of cardiovascular disease. Results of these trials have called into question existing dogma from epidemiological and basic science studies that estrogen provides protection against development of cardiovascular disease. When studies are evaluated for design, type and duration of hormone treatment, and outcomes, directions for future research become apparent. Improved hormone formulations and selective estrogen receptor modulators that help to maintain vascular function and limit progression of cardiovascular occlusive disease need to be developed. This will depend upon improved understanding of: (i) the distribution and regulation of estrogen receptors in vascular tissue, (ii) genomic interactions of estrogens and progestins, (iii) association of the estrogen receptor and other genetic polymorphisms with particular vascular functions, and (iv) better definition of timing and dosing for therapeutic intervention. The mechanisms of interactions between coagulation proteins, inflammatory cytokines, platelets and the vessel wall should be defined so that the thrombotic risk for an individual woman can be identified and reduced, and progression of chronic disease processes associated with loss of ovarian hormones can be slowed.