Equine-derived estrogen may hold higher risk than estradiol

Two types of pharmaceutical estrogens prescribed to women to manage postmenopausal symptoms may have differing safety profiles. An observational study published online Sept. 30 in JAMA Internal Medicine found women taking oral conjugated equine estrogens (CEEs) had a higher risk of venous thrombosis (VT) compared with those taking oral estradiol.

Nicholas L. Smith, PhD, of the University of Washington in Seattle, and colleagues used the Heart and Vascular Health Study to compare the safety of the two estrogen types. The study draws its data from the Group Health Cooperative, a large health maintenance organization with a computerized pharmaceutical database.

For this analysis, they focused on postmenopausal women who took either CEE or estradiol between 2003 and 2009 and identified cases of incident deep vein thrombosis or pulmonary embolism (VT, 68 women), MI (67 women) and ischemic stroke (48 women). The study included a control group of 201 postmenopausal women taking hormone therapy with no history of these events; a subset of 140 controls agreed to donate a blood sample. None of the women were on anticoagulants.  

Smith et al reported women currently using oral CEE had a greater risk of VT compared with women on estradiol (odds ratio 2.08). They also noted an increased risk of MI that was not statistically significant (odds ratio 1.87) and no associated risk for ischemic stroke.

To analyze thrombotic potential, they tested the control blood samples for resistance to activated protein C (APC). They found controls on CEEs had greater resistance to APC compared with women on estradiol, “providing biological support for the increased risk seen in the case-control analysis.”

“How estrogenic compounds modulate thrombotic risk remains poorly understood, and our data suggest that risk potential may vary by the types or amounts of estrogen-derived molecules within various marketed estrogens,” they wrote.

Smith et al emphasized that their study had several limitations and that the results needed to be replicated. If confirmed, the findings could help patients and physicians make better informed safety decisions about hormone therapy.