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Postmenopausal oral estrogen therapy and blood pressure in normotensive and hypertensive subjects: the Estrogen in the Prevention of Atherosclerosis Trial

Steiner, Anne Z MD, MPH1; Hodis, Howard N MD2,3,4; Lobo, Rogerio A MD5; Shoupe, Donna MD1; Xiang, Min MS3; Mack, Wendy J PhD3,4

doi: 10.1097/01.gme.0000184426.81190.01

Objective: To determine if 17β-estradiol increases blood pressure in postmenopausal women.

Design: A total of 222 healthy postmenopausal women were randomly assigned to either 1 mg micronized 17β-estradiol daily or placebo for 2 years. Blood pressure measurements were obtained every other month and common carotid artery intima-media thickness measured every 6 months. Statistical analyses comparing longitudinal changes in systolic and diastolic blood pressure between treatment groups used a mixed general linear model including interaction terms to evaluate variations by age or estradiol level.

Results: Both placebo and estradiol groups showed small declines in systolic and diastolic blood pressure during the trial among the normotensive subjects and subjects on antihypertensive medications. However, the decline did not differ significantly between the groups. Treatment effects on systolic blood pressure differed significantly by the age of the subject (interaction P value = 0.04) with younger women on estradiol showing on average a rise in systolic blood pressure, and older women a decline. The association between serum estradiol level and systolic blood pressure showed a similar modification with age (P = 0.03). Changes in systolic blood pressure in women on estradiol were positively correlated with intima-media thickness progression (P = 0.03).

Conclusions: Overall, 17β-estradiol did not influence changes in blood pressure in normotensive or hypertensive women. The effect of 17β-estradiol treatment on systolic blood pressure may be influenced by a woman's age. Estradiol may increase systolic blood pressure in younger postmenopausal women, while having the opposite effect in older postmenopausal women.

Estrogen therapy does not exacerbate hypertension in women well controlled on antihypertensive medications. Blood pressure response to estrogen therapy may be age dependent.

From the Departments of 1Obstetrics and Gynecology, 2Medicine and 3Preventive Medicine, and the 4Atherosclerosis Research Unit, University of Southern California/Keck School of Medicine, Los Angeles, CA; and 5Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY.

Received December 30, 2004; revised and accepted April 13, 2005.

This study was supported by the National Institute on Aging, National Institutes of Health R01-AG-18798.

Address correspondence to: Wendy J. Mack, PhD, USC Keck School of Medicine, Department of Preventive Medicine, 1540 Alcazar Street, CHP 222, Los Angeles, CA 90033. E-mail:

©2005The North American Menopause Society