March 27, 2014
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Estradiol preserved brain metabolism in postmenopausal women at risk for dementia

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In postmenopausal women considered at risk for dementia, continued treatment with 17-beta-estradiol hormone therapy is associated with the preservation of regional cerebral cortical metabolism for at least 2 years, according to recent findings.

Moreover, 17-beta-estradiol was found to sustain metabolism of the precuneus/posterior cingulate cortical (PCC) region of the brain, which is known to undergo significant metabolic decrements in the early stages of Alzheimer’s disease.

In the prospective, randomized trial, researchers evaluated 64 postmenopausal women (mean age, 58 years) considered at risk for dementia. Of the 64 participants, 32 were randomly assigned to continue their HT regimen after an average of 10 years of use, and 32 were assigned to discontinue HT. They were followed up for 2 years.

Of those in the intervention group, 30 completed the 2-year follow-up, and 28 were included for analysis (two were excluded due to problems with PET scans). Of these women, 16 underwent HT with 17-beta-estradiol, whereas 12 followed a regimen of treatment with conjugated equine estrogens (CEE).

Variations in cerebral metabolism were measured through pre- and post-study neuroimaging using PET scans and MRI imaging, as well as through cognitive function testing.

Longitudinal data was accessible for 45 participants who completed the study.

The researchers found that frontal and parietal cortical metabolism was relatively preserved in the women assigned to continue HT vs. those who discontinued HT. Notably, although significant metabolic declines in the PCC area of the brain were discovered in women who discontinued the use of 17-beta-estradiol, women who continued HT with CEE also demonstrated a decline in PCC metabolism. Significant PCC metabolic reductions were also observed in participants who were taking concomitant progestins.

According to the researchers, these studies suggest a specific benefit from continuation of unopposed 17-beta-estradiol therapy in combating cerebral decline. However, study researcher Natalie Rasgon, MD, professor of psychiatry and behavioral sciences at the Stanford University School of Medicine, said the benefits of 17-beta-estradiol HT must be weighed against its potential risks.

“We hadn’t expected the type of estrogen therapy to have such a distinct effect on the brain,” Rasgon said in a press release. “Still, estradiol’s effects on the body aren’t entirely benign. For example, exposure to the hormone raises the risk of breast and uterine cancer. Perimenopausal women with risk factors for dementia should talk to their doctors about whether estradiol-based hormone therapy makes sense.”

Disclosure: The researchers report no relevant financial disclosures.