Estradiol's Effect on Blood Pressure Varies With Age

March 28, 2005

Jane Neff Rollins, MSPH

March 28, 2005 (Los Angeles) — Estradiol therapy may increase systolic blood pressure (SBP) in younger women but may have beneficial effects on SBP in older women, according to a presentation given here by Anne Z. Steiner, MD, MPH, from the University of Southern California Keck School of Medicine in Los Angeles, at the 52nd annual meeting of the Society for Gynecologic Investigation.

"Younger women on estradiol showed an increase in blood pressure over the two years, while older women on estradiol showed a blood pressure decline," Dr. Steiner told meeting attendees.

The Women's Health Initiative (WHI) identified increased rates of cardiovascular events and ischemic stroke among postmenopausal women receiving combination estrogen and progestin replacement therapy. Blood pressure was higher in postmenopausal women even after adjusting for age. Because relatively small increases in SBP increase the risk of stroke and cardiovascular disease, Dr. Steiner and her team hypothesized that the mechanism leading to adverse cardiovascular events seen in the WHI may have been driven by changes in blood pressure.

The aims of the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) were to determine the effects of 17β-estradiol treatment on blood pressure in postmenopausal women and how age influences this effect. In addition, because the common carotid intima media is thicker in postmenopausal women than in premenopausal women, the investigators examined whether changes in blood pressure correlate with the progression in intima media thickness (IMT), a marker for atherosclerosis.

The investigators randomized 222 healthy postmenopausal women without preexisting cardiovascular disease to one of two equal-sized groups (n = 111). Eligibility criteria included age older than 45 years (range, 46-80 years), no history of menopausal hormone therapy (HT) for more than 10 years nor use of HT within the month before enrollment, not currently smoking (50% of participants were former smokers), and fasting blood glucose levels less than 200 mg/dL if the participant was diabetic. Hypertension was not an exclusion criterion if it was well-controlled with antihypertensive medication, and approximately 20% of participants fell into this category.

The women in the treatment group received 1 mg of micronized 17β-estradiol daily for the two-year study period. The control group received placebo. Participants had their blood pressure measured at least every other month during the enrollment period and subsequently every six months. IMT was measured every six months throughout the trial.

Statistical analyses compared longitudinal changes in SBP and diastolic blood pressure (DBP) between groups using a mixed general linear model. Interaction terms were added to evaluate whether the rate of change in blood pressure varied by age or estradiol level.

SBP and DBP decreased in both the placebo and estradiol groups, regardless of whether subjects' initial blood pressure values were normal and elevated. This was considered important because most observational studies of blood pressure in postmenopausal women show that control group participants generally experience an increase in blood pressure.

Interestingly, patients in the estradiol group who had high blood pressure well-controlled on antihypertensive therapy at baseline did not experience increased blood pressure. "In women who are well-controlled on antihypertensive therapy, HT should not be a contraindication," Dr. Steiner told Medscape.

Subgroup analyses showed that treatment effects on SBP differed significantly by the age of the subject ( P = .04 for age multiplied by treatment multiplied by time on-study interaction). Higher serum estradiol levels were associated with a statistically nonsignificant rise in SBP (0.016 mm Hg per year of treatment and pg/mL of serum estradiol; P = .15). The positive relationship between serum estradiol level and SBP rate change decreased significantly with age (-0.00326 mm Hg per year of treatment, pg/mL of serum estradiol, and age; P = .03).

Changes in IMT mirrored changes in SBP. Among women in the estradiol group, increases in SBP were associated with increases in IMT progression ( P = .03) and were also influenced by the woman's age. Patients whose SBP declined also showed a decline in IMT, while those whose SBP increased also experienced an increase in IMT. Combined, these data suggest that women older than 65 years treated with estradiol may be less likely to experience progression of atherosclerosis and stroke than younger women on estradiol.

Dr. Steiner added that clinicians "can be confident in continuing HT in patients with well-controlled hypertension," but she cautioned that clinicians should not change their HT prescribing practice based on these data, which were based on a secondary, post-hoc analysis. The results have more of a role in hypothesis generating when investigators design future studies.

The National Institutes of Health sponsored this study.

SGI 52nd Annual Meeting: Abstract 315. Presented March 24, 2005.

Reviewed by Gary D. Vogin, MD

Jane Neff Rollins, MSPH, is a freelance writer for Medscape.


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