Menopausal hormone therapy & cardiovascular disease: It’s a wash

Low-dose hormone therapy (LHT) in early menopausal women already at low risk for cardiovascular disease did not significantly affect carotid artery intima-media thickness (CIMT) or coronary artery calcium (CAC), according to a study published online July 29 in Annals of Internal Medicine.

The Kronos Early Estrogen Prevention Study (KEEPS) enrolled healthy menopausal women to determine if either low-dose transdermal 17β-estradiol (t-E2) or oral conjugated equine estrogens (o-CEE) with oral progesterone had an influence on both symptoms of menopause and cardiovascular disease. KEEPS took place between July 2005 and June 2008.

The research team, led by S. Mitchell Harman, MD, PhD, from Phoenix Veterans Affairs Health Care System in Arizona, found that for the 89.3 percent of women who were followed up, the rate of CIMT increase was similar, at a mean of 0.0076 mm per year. Between the o-CEE and placebo groups, the rate difference was 0.0008 mm per year, while between the t-E2 and the placebo, the difference was 0.0005 mm per year.

When CAC was assessed, CAC scores had increased in all three groups, with the greatest percent increase in the placebo group. However, the differences between o-CEE and placebo and t-E2 and placebo were not considered significant by the research team (3.6 percent lower in o-CEE group and 2.1 percent lower in the t-E2 group). In women with a baseline of greater than one Agatston unit, CAC progressed in 26 percent of the placebo group, 19 percent in the o-CEE group and 22 percent in the t-E2 group.

No change was seen in blood pressure between the hormone groups and the placebo.

While patients did experience some relief from menopausal symptoms, this approach used estrogen doses lower than those used in prior studies where a protective effect was seen.

Harman et al stated that while some indicators for cardiovascular disease and atherosclerosis were decreased, such as low-density lipoprotein (with o-CEE), other biomarkers, such as high-density lipoprotein, c-reactive protein and sex hormone-binding globulin increased. T-E2 had a decrease in levels of cholesterol (in particular non-high-density lipoprotein), insulin and insulin resistance scores. No differences were seen between the three groups in interleukin-6 levels.

As a result, Harman et al suggested that menopausal hormone therapy may not be the best clinical approach to reducing cardiovascular risks in this population, but neither does it place patients at increased risk for cardiovascular events.