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CEE (0.625 mg/d) administered orally, with or without MPA, is associated with an increased risk of hypertension in older postmenopausal women. Whether lower doses, different estrogen formulations, or transdermal route of administration offer lower risks warrant further study.

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Objectives Mean and visit-to-visit variability (VVV) of blood pressure are associated with an increased cardiovascular disease risk. We examined the effect of hormone therapy on mean and VVV of blood pressure in postmenopausal women from the Women’s Health Initiative (WHI) randomized controlled trials. Methods Blood pressure was measured at baseline and annually in the two WHI hormone therapy trials in which 10,739 and 16,608 postmenopausal women were randomized to conjugated equine estrogens (CEE, 0.625 mg/day) or placebo, and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) or placebo, respectively. Results At the first annual visit (Year 1), mean systolic blood pressure was 1.04 mmHg (95% CI 0.58, 1.50) and 1.35 mmHg (95% CI 0.99, 1.72) higher in the CEE and CEE+MPA arms respectively compared to corresponding placebos. These effects remained stable after Year 1. CEE also increased VVV of systolic blood pressure (ratio of VVV in CEE vs. placebo, 1.03, P<0.001), whereas CEE+MPA did not (ratio of VVV in CEE+MPA vs. placebo, 1.01, P=0.20). After accounting for study drug adherence, the effects of CEE and CEE+MPA on mean systolic blood pressure increased at Year 1, and the differences in the CEE and CEE+MPA arms vs. placebos also continued to increase after Year 1. Further, both CEE and CEE+MPA significantly increased VVV of systolic blood pressure (ratio of VVV in CEE vs. placebo, 1.04, P<0.001; ratio of VVV in CEE+MPA vs. placebo, 1.05, P<0.001). Conclusions Among postmenopausal women, CEE and CEE+MPA at conventional doses increased mean and VVV of systolic blood pressure.