Estrogen plus progestin and the risk of peripheral arterial disease: the Women's Health Initiative.
BACKGROUND
Observational studies have reported less frequent carotid atherosclerosis in healthy women taking postmenopausal hormone therapy. Estrogen with progestin did not reduce peripheral arterial events among women with preexisting coronary heart disease. This analysis evaluates clinical peripheral arterial disease among generally healthy women in the Women's Health Initiative randomized trial of estrogen plus progestin.


RESULTS
The Estrogen Plus Progestin trial assigned 16 608 postmenopausal women, mean age 63.3+/-7.1 years, to daily conjugated estrogens (0.625 mg) with medroxyprogesterone acetate (2.5 mg) or placebo and documented health outcomes over an average of 5.6 years of follow-up. Hospitalization for peripheral arterial disease was infrequent, with annualized rates of 0.08%, 0.06%, and 0.02% for carotid disease, lower extremity arterial disease, and abdominal aortic aneurysm, respectively. The incidence of peripheral arterial events did not differ between treatment groups (hazard ratio [HR] 0.89, 95% confidence interval 0.63, 1.25). The risk was slightly greater among women assigned to active estrogen with progestin in years 1 (HR 1.33) and 2 (HR 1.27), and was slightly lower in later years (HR 0.85 and 0.87 in years 5 and > or =6). Among adherent participants, the hazard ratio for peripheral arterial events was 1.23 (95% confidence interval 0.79, 1.91) over the 5.6 years of follow up. Subgroup analysis identified no significant interactions between estrogen with progestin and baseline characteristics with regard to peripheral arterial disease risk.


CONCLUSIONS
Among generally healthy postmenopausal women, conjugated estrogens with progestin did not confer protection against peripheral arterial disease.
Hsia
Judith
J
Department of Medicine, George Washington University, Washington, DC, USA. jhsia@mfa.gwu.edu
Criqui
Michael H
MH
Rodabough
Rebecca J
RJ
Langer
Robert D
RD
Resnick
Helaine E
HE
Phillips
Lawrence S
LS
Allison
Matthew
M
Bonds
Denise E
DE
Masaki
Kamal
K
Caralis
Panagiota
P
Kotchen
Jane M
JM
D000368:Aged; D001158:Arteries; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D012307:Risk Factors; D017211:Treatment Failure
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate