This population-based, case-control safety study was designed to compare the relative clinical cardiovascular safety of two commonly used oral estrogen drugs—conjugated equine estrogens (CEEs) and estradiol. Cases were postmenopausal women who had experienced an incident myocardial infarction (MI; n=67), ischemic stroke (n=48), or venous thrombosis (VT - deep vein thrombosis or pulmonary embolism; n= 68) and had no history of VT, MI, or ischemic stroke events. Controls (n=201) were postmenopausal women who had no history of VT, MI, or ischemic stroke. All cases and controls were using oral CEEs or estradiol from 2003 onwards since HRT use changed dramatically after the June 2002 publication of the first Women’s Health Initiative trial results. Neither cases nor controls were using anticoagulants.
After a six year follow up, there was a greater risk of VT associated with current oral CEEs use than with current oral estradiol use (primary endpoint; OR, 2.08; 95% CI, 1.02-4.27; P = 0.045). Current oral CEEs use was also associated with an increase in MI risk (secondary endpoint; OR, 1.87; 95% CI, 0.91-3.84; P = 0.09) that did not reach statistical significance and there was no increased risk for ischemic stroke (secondary endpoint; OR, 1.13; 95% CI, 0.55-2.31; P = 0.74).
Along with the limitations inherent to case-control studies, the authors note that these data do not directly address the relative risk of initiating HRT. They add that data suggest that oral estrogen drugs have different levels of cardiovascular risk and require further study.