Are CEEs Associated With a Higher Venous Thrombosis Risk Than Estradiol?

Among postmenopausal women, conjugated equine estrogens (CEEs), as compared to estradiol, are associated with a greater incidence of venous thrombosis, according to new observational data published Sept. 30 in JAMA Internal Medicine.

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The study looked at the incidence of venous thrombosis, MI and stroke among 384 postmenopausal women using oral hormone therapy. The risk of venous thrombosis was significantly increased among CEE users as compared to estradiol users (odds ratio, 2.08; 95 percent CI, 1.02-4.27; p=0.045). There also was a trend towards an increased risk of MI that did not reach statistical significance (p=0.09). The incidence of stroke risk was comparable in both groups. CEE users had higher endogenous thrombin potential-based normalized activated protein C sensitivity ratios (p<0.001), indicating a stronger tendency towards clotting.

Unique to this study's designs was allocation of treatment, which was not based on patient-specific factors. Rather, it was based on the time at which hormone therapy was initiated. "This quasiexperimental design ... overcomes some biases associated with nonrandom treatment allocation," wrote the investigators.

Strengths included a population-based design and the verification of thrombotic events with biological data, the investigators note. However, they add that the results might be limited by a small number of patients newly treated with CCEs, as well as unrecognized confounders and biases.

"These results need replication but suggest that oral estrogen drugs have different levels of cardiovascular risk," they concluded. They add that if their results are confirmed, it would "provide valuable information to women and their health care professionals when making safety decisions regarding available hormone therapy options for menopausal symptom management."

Keywords: Protein C, Menopause, Risk, Stroke, Thrombin, Estradiol, Estrogens, Conjugated (USP), Cardiovascular Diseases, Venous Thrombosis

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