Conjugated equine estrogens and peripheral arterial disease risk: The Women's Health Initiative

Background: Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted. Methods: The Estrogen Alone trial randomized 10 739 postmenopausal women with prior hysterectomy, mean age 63.6 ± 7.3 years, to conjugated equine estrogens (CEE 0.625 mg/d) or placebo and documented health outcomes over an average of 7.1 ± 1.6 years. Results: A trend toward increased risk of peripheral arterial events with CEE was observed (hazard ratio [HR] 1.32, 95% CI 0.99-1.77). Carotid arterial events (HR 1.19, 95% CI 0.82-1.74), lower extremity arterial events (HR 1.41, 95% CI 0.86-2.32), and abdominal aortic aneurysm (HR 2.40, 95% CI 0.92-6.23) were more frequent, but not individually significant, in the CEE group. However, the composite of lower extremity arterial disease/abdominal aortic aneurysm was significantly more frequent among women assigned to CEE (HR 1.63, 95 % CI 1.05-2.51). In subgroup analyses, no clear pattern of risk with CEE was apparent by age or by time since menopause. Conclusions: Unopposed CEE conferred no protection against peripheral arterial disease among generally healthy postmenopausal women; in fact, there was a suggestion of increased risk.