PARADOXICAL INFLUENCE OF ESTROGENIC HORMONES ON PLATELET-ENDOTHELIAL CELL-INTERACTIONS

Controversies abound in the literature about the safety and efficacy o f tamoxifen and estrogen. We studied the effect of these 2 hormonal ag ents on factors involved in in vitro thrombogenesis: platelets and end othelial cells. Endothelial cells were derived from human umbilical ve ins and platelets were obtained from premenopausal and postmenopausal women, women on oral contraceptives, postmenopausal women on hormone r eplacement therapy, men, and patients with breast cancer who had been taking adjuvant tamoxifen for more than 1 year. The interaction of pla telets with endothelial cell matrix was measured in 2 systems: 1) in a flow chamber at low shear rate and, 2) with Cr-51 labeled platelets i n a ''static'' culture system. In the static system, platelets from wo men on tamoxifen exhibited decreased platelet adherence to endothelial cell matrix whether they were grown in tamoxifen or control condition s, when compared to platelets from premenopausal women. When flow (25 sec(-1)) was added these differences were negated. Neither tamoxifen n or 17 beta estradiol had an effect on endothelial cell proliferation o r platelet aggregation. Adhesion of platelets at low shear was not alt ered when platelet rich plasma was incubated with tamoxifen nor when e ndothelial cells were grown in tamoxifen. In contrasts, incubation of platelets in 17 beta estradiol decreased platelet adhesion at low shea r rate, however, there was no effect on platelet adhesion when endothe lial cells were grown in 17 beta estradiol. We conclude that in early stages of thrombus formation as measured in vitro, tamoxifen may not h ave a detrimental effect and estrogen may be protective.