Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens

Study Questions:

What is the relative clinical cardiovascular safety profile of conjugated equine estrogens (CEEs) and estradiol, two of the most commonly used oral estrogen drugs used by women?


Data from the Heart and Vascular Health Study, a case-control study of incident cardiovascular events, were used for the present analysis. All subjects were members of Group Health Cooperative, a large health maintenance organization in Washington state. Cases included first venous thrombosis (VT), myocardial infarction (MI), stroke, and atrial fibrillation events. Case identification began on January 1, 1989, and continued through December 2009. The control group was frequency matched 3:1 to the largest case group (MI) by sex, age within decade, treated hypertension status, and calendar year of identification. For the present analysis, participants were limited to postmenopausal women using oral hormonal therapy (HT) from January 1, 2003, forward. Thus, participants were 384 postmenopausal women ages 30-79 years using oral HT.


From January 1, 2003, through December 31, 2009, there were 68, 67, and 48 postmenopausal women who experienced an incident VT, MI, or ischemic stroke event, respectively, and 201 controls, all of whom were current users of oral CEEs or estradiol. In adjusted analyses, current oral CEE use compared with current oral estradiol use was associated with an increased VT risk (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.02-4.27; p = 0.045) and an increased MI risk that did not reach statistical significance (OR, 1.87; 95% CI, 0.91-3.84; p = 0.09) and was not associated with ischemic stroke risk (OR, 1.13; 95% CI, 0.55-2.31; p = 0.74). Among 140 controls, CEE users compared with estradiol users had higher endogenous thrombin potential–based normalized activated protein C sensitivity ratios (p < 0.001), indicating a stronger clotting propensity.


The investigators concluded that in an observational study of oral HT users, CEE use was associated with a higher risk of incident VT and possibly MI than estradiol use.


Studies such as this provide data on real-world women, which will allow clinicians to understand the cardiovascular risk related to different hormonal therapies. Further research is needed to improve our understanding of the risks and benefits of HT for postmenopausal women.

Clinical Topics: Prevention, Vascular Medicine, Hypertension

Keywords: Washington, Myocardial Infarction, Stroke, Postmenopause, Cardiovascular Diseases, Venous Thrombosis, Estrogen Replacement Therapy, Hypertension

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