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Effects of estradiol and the angiotensin II receptor blocker irbesartan on vascular function in postmenopausal women

Mirza, Faryal S. MD1; Ong, Paul MD3; Collins, Peter MD3; Okamura, Kyoko MD, MPH1; Gerhard-Herman, Marie MD2; Williams, Gordon H. MD1; Seely, Ellen W. MD1

doi: 10.1097/gme.0b013e318150d13e

Objective: Estradiol and angiotensin receptor blockers have prominent effects on the renin-angiotensin-aldosterone system. The purpose of this study was to determine whether irbesartan, an angiotensin receptor blocker, has a greater effect on vascular function when combined with estradiol, compared with irbesartan alone, in hypertensive postmenopausal women.

Design: Fifty-one women were studied while off any antihypertensive medications or hormone therapy at baseline and after randomization to one of four treatment arms for 12 weeks: (1) irbesartan and estradiol, (2) irbesartan and placebo, (3) estradiol and placebo, and (4) placebo/placebo. Estradiol and placebo arms served as control groups. Blood pressure, brachial reactivity, aldosterone, insulin, glucose, 24-hour urinary catecholamines, urinary sodium, and creatinine were measured. Fisher's exact test was used for comparison of differences in blood pressure in the treatment arms. Paired t test and analysis of variance were also performed for within- and between-group analysis.

Results: A significantly larger number of women in the irbesartan and estradiol group had a decrease of 5 mm Hg or more in both systolic and diastolic blood pressures (P < 0.05) compared with irbesartan alone group. Forearm vascular reactivity was increased significantly compared with baseline (P < 0.05), and there was a significant decrease in the serum aldosterone level after treatment compared with baseline (P < 0.05) in the irbesartan and estradiol combination group. Fasting glucose and insulin, urinary sodium/creatinine ratio, and catecholamines were similar at each time point.

Conclusions: The results suggest that irbesartan and estradiol, when used in combination, may cause a greater lowering of blood pressure in postmenopausal hypertensive women. This effect may be mediated via increased vasodilation and lower aldosterone levels. These results warrant further testing in larger clinical trials.

Postmenopausal hypertensive women were treated with irbesartan, an angiotensin receptor blocker, with and without the addition of estradiol. A significantly larger number of women in the irbesartan and estradiol combination group had a reduction in both systolic and diastolic blood pressures compared with the irbesartan alone group, suggesting that estradiol may augment the antihypertensive effect of irbesartan.

From the 1Division of Endocrinology, Diabetes, and Hypertension and 2Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; and 3Department of Cardiovascular Medicine, Royal Brompton Hospital, London, UK.

Received February 2, 2007; revised and accepted July 11, 2007.

Funding/support: GCRC at Brigham and Women's Hospital HL67332, SCOR in Hypertension HL 55000, R01 RR 002635 (E.W.S.), K24 RR 018613 (E.W.S), Bristol-Myers Squibb Company.

Financial disclosure: None reported.

Address correspondence to: Ellen W. Seely, MD, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115. E-mail:

©2008The North American Menopause Society