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 10739 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.
Hsia
Judith
J
Department of Medicine, George Washington University, Washington, DC, USA. jhsia@mfa.gwu.edu
Criqui
Michael H
MH
Herrington
David M
DM
Manson
Joann E
JE
Wu
Lieling
L
Heckbert
Susan R
SR
Allison
Matthew
M
McDermott
Mary McGrae
MM
Robinson
Jennifer
J
Masaki
Kamal
K
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D035002:Lower Extremity; D008875:Middle Aged; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016387:Women's Health
D004967:Estrogens; D004966:Estrogens, Conjugated (USP)