February 06, 2020
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Type of estrogen therapy influences heart fat deposition among postmenopausal women

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Samar R. El Khoudary

Among healthy, postmenopausal women, hormone therapy with oral conjugated equine estrogens — compared with transdermal estradiol or no hormone therapy — may slow the adverse effects of heart fat accumulation on carotid intima-media thickness, according to an analysis of the KEEPS study published in Menopause.

“Consistent with our previous work within the Study of Women’s Health Across the Nation (SWAN), the current findings from the Kronos Early Estrogen Prevention Study (KEEPS) trial support a contribution of estrogen to the pathophysiological consequences of paracardial fat depot in midlife women,” Samar R. El Khoudary, PhD, MPH, BPharm, FAHA, associate professor of epidemiology at the Epidemiology Data Center, University of Pittsburgh, told Healio. “Within KEEPS, we found that the use of HT in recent menopausal women modifies the associations between paracardial fat and carotid intima-media thickness, a subclinical measure of atherosclerosis found to deteriorate in midlife women. The reported effect modification of HT use depends on the HT formulation and/or route of administration. Our results suggest that compared to transdermal estradiol, the use of oral conjugated equine estrogens may slow down the adverse impacts of paracardial fat on carotid intima-media thickness progression in recently menopausal women.”

El Khoudary and colleagues analyzed data from 467 women who were menopausal for an average of 1.8 years who participated in KEEPS, a randomized, placebo-controlled trial assessing the effects of 0.45 mg per day of oral conjugated equine estrogens (n = 140) and 50 µg per day of transdermal 17beta-estradiol (n = 144), compared with placebo (n = 183), on 48 months’ progression of carotid intima-media thickness (CIMT; mean age, 53 years; 78.2% white). Researchers used CT to measure epicardial adipose tissue, paracardial adipose tissue and CIMT at baseline and 48 months.

At 48 months, mean overall CIMT progression across treatment arms was 33 µm. Progression did not differ by treatment group as reported previously, according to researchers; the geometric mean of 48-month CIMT progression was 31.9 µm for women assigned conjugated estrogens, 35.1 µm for women assigned transdermal 17beta-estradiol and 33 µm for women assigned placebo (P = .82).

 
Among healthy, postmenopausal women, hormone therapy with oral conjugated equine estrogens — compared with transdermal estradiol or no hormone therapy — may slow the adverse effects of heart fat accumulation on carotid intima-media thickness.
Source: Adobe Stock

Researchers found that 48-month changes in CIMT were not associated with either baseline epicardial adipose tissue or paracardial adipose tissue, or changes in epicardial adipose tissue or paracardial adipose tissue, with results persisting in fully adjusted analysis.

However, estimated CIMT progression based on changes in paracardial adipose tissue differed across the study groups in adjusted models (P = .04).

For women in the conjugated estrogens group, the estimated CIMT progression per 1 standard deviation increase in paracardial adipose tissue was 12.66 µm (95% CI, 1.8-23.52) lower than the estimated effect in the transdermal 17beta-estradiol group (P = .02), and was 10.09 µm (95% CI, 0.79-19.39) lower than the estimated effect for the placebo group (P = .03).

“Whether this beneficial impact on CIMT is due to use of conjugated equine estrogens or the oral route of administration is unclear and should be assessed in future studies,” the researchers wrote. – by Regina Schaffer

For more information:

Samar R. El Khoudary, PhD, MPH, BPharm, FAHA, can be reached at the Epidemiology Data Center, University of Pittsburgh, 4420 Bayard St., Suite 600, Pittsburgh, PA 15260; email: elkhoudary@edc.pitt.edu.

Disclosures: The KEEPS trial was sponsored by Abbott Pharmaceuticals, The Aurora Foundation, Bayer HealthCare and Pfizer Pharmaceuticals. El Khoudary reports no relevant financial disclosures. Please see the study for all authors’ relevant financial disclosures.