Concurrent administration of sustained-release bezafibrate may counteract the increased thrombotic risk associated with oral estrogen therapy.

Although hormone replacement therapy (HRT) can have many favorable effects on serum lipids and on vascular endothelium that presumably mediate the decreased risk for heart attack and stroke associated with HRT in observational epidemiology, oral estrogen also has various pro-coagulant effects: increases in serum triglycerides and factor VII activity, decreases in serum antithrombin III and protein S. This may explain the increased risk for venous thromboembolism observed with HRT and oral contraceptives, as well as the temporary increase in coronary risk noted when women with preexisting coronary disease initiate HRT. The well-tolerated hypolipidemic agent bezafibrate has anticoagulant actions that are diametrically opposed to the procoagulant effects of oral estrogen: namely, reductions in serum triglycerides and factor VII activity, and an increase in antithrombin III. However, bezafibrate could be expected to complement the protective effects of oral estrogen on serum lipids and on serum IGF-I activity. Thus, there is reason to believe that concurrent bezafibrate administration would minimize any thrombotic risk associated with HRT or oral contraception, while amplifying the health benefits of oral estrogen, and would make it more feasible to administer these therapies in women at increased vascular risk. These predictions require confirmation in controlled clinical studies. Certain natural hypolipidemic agents may also have potential as adjuvants to oral estrogen, but their effects on hemostasis require further investigation.