Effects of Estrogen Replacement Therapies on Mouse Platelet Function and Glycoprotein VI

Clinical trials have shown estrogen replacement therapy (ERT) is associated with adverse arterial vascular events. Arterial thrombosis is initiated by platelet activation, but the in vivo effects of estrogens on platelet function are not well understood. We used a murine model of menopause to examine 3 major ERT regimes and test the hypothesis that ERT affects the intrinsic platelet response to ago-nists. The 3 ERT regimes studied were: (1) oral conju-gated equine estrogen (CEE), (2) oral 17- estradiol (E2), and (3) subcutaneously implanted E2 (SQ E2). Paired ovariectomized littermates were treated with these re-gimes or placebo for 21 days. Two platelet agonists, thrombin and the GPVI-specific agonist collagen-related peptide (COL-RP), were used to evaluate platelet reac-tivity. Among the 3 regimens, (1) oral CEE enhance