North American Menopause Society
North American Menopause Society
Perspective from Pauline M. Maki, PhD
Source:

Kantarci K. How to KEEP sharp: The KEEPS cognition follow-up. Presented at: North American Menopause Society Annual Meeting; Sept. 28-Oct. 3, 2020 (virtual meeting).

Disclosures: Kantarci reports the research was supported by Alzheimer’s Drug Discovery Foundation, Eli Lilly and NIH.
October 05, 2020
4 min read
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Brain effects of menopausal HT differ for pill, patch delivery

Perspective from Pauline M. Maki, PhD
Source:

Kantarci K. How to KEEP sharp: The KEEPS cognition follow-up. Presented at: North American Menopause Society Annual Meeting; Sept. 28-Oct. 3, 2020 (virtual meeting).

Disclosures: Kantarci reports the research was supported by Alzheimer’s Drug Discovery Foundation, Eli Lilly and NIH.
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Early menopausal women experienced different changes in cognitive health imaging biomarkers based on route of delivery of hormone therapy vs. placebo in the Kronos Early Estrogen Prevention Study, according to a speaker.

Kejal Kantarci

“Effects of early menopausal HT on imaging biomarkers of cognitive health differ by the formulations and administration routes,” Kejal Kantarci, MD, MS, professor of radiology and director at Mayo Clinic Women’s Health Research Center and associate director at Mayo Clinic Alzheimer’s Disease Research Center, told Healio. “We are at the beginning of our investigation. More research is needed to determine the biological reasons behind brain changes during menopausal HT.”

Image of more brain scans
Source: Adobe Stock

Kantarci presented findings at the North American Menopause Society virtual meeting.

The Kronos Early Estrogen Prevention Study (KEEPS) enrolled 727 women aged 42 to 58 years who were within 36 months of their last menses and had no prior CVD events. The participants were enrolled from 2005 to 2009 at nine U.S. academic sites and were randomly assigned to treatment with 0.45 mg oral conjugated equine estrogen pills (Premarin, Pfizer) daily or a 50 ug transdermal 17-beta-estradiol patch (Climara, Bayer) or to placebo pills or patch. Oral micronized progesterone was given to active treatment groups 12 days each month.

Within the trial, 118 participants at the Mayo Clinic site also participated in a neuroimaging study to assess the effects of HT on imaging biomarkers of cognitive health. The women underwent MRI and cognitive testing at baseline, 18, 36 and 48 months within the KEEPS trial period. Participants also underwent MRI and cognitive test 84 months after baseline, or 3 years after the trial concluded.

HT effects on brain volume, white matter hyperintensities

Scans at 48 months showed no difference in the decline in brain volume for HT users vs. the placebo groups, whereas women who received oral HT had a greater increase in ventricular expansion vs. placebo (P = .03). However, 3 years after the trial ended, there was no difference in the rate of increase of ventricular expansion, suggesting the rate of change disappears after HT ends, Kantarci said. No change in cognitive function was found between the groups.

Researchers also analyzed aortic hemodynamics preceding hypertension in KEEPS participants who were normotensive (n = 53; mean age, 60 years). Greater increases in white matter hyperintensities were seen in the oral HT group vs. placebo (P = .03) at 84 months. Women with a greater amount of thrombogenic microvesicles in the blood had larger increases in white matter hyperintensities.

“The thrombogenic properties of estrogens, particularly the oral conjugated equine estrogen formulation, may be responsible for the accelerated increases in the white matter hyperintensities in women who were on menopausal HT,” Kantarci said during the presentation.

Prefrontal cortex, amyloid-beta deposition analysis

Analysis of the prefrontal cortex showed more volume was preserved in the group assigned patch HT vs. placebo. There was no significant difference between oral HT and placebo.

Researchers also conducted a cross-sectional study at 84 months using PET imaging to measure beta-amyloid loads in the brain. Overall, women in the transdermal estradiol group had the lowest level of amyloid-beta deposition. When beta-amyloid results were compared with prefrontal cortex volume measurements, an association was found linking lower beta-amyloid levels to greater preservation of the prefrontal cortex for the transdermal estradiol group (P < .01). There was no association found in either the placebo or oral estrogen groups.

“It is interesting that participants who took estradiol via skin patches maintained brain volume in the dorsolateral prefrontal cortex, an area of the brain that assists with memory, thinking, planning and reasoning, over the 7 years of the study,” Kantarci said. “Women who maintained volume in this area of the brain were also more likely to have a lower amount of the amyloid plaque deposits that are related to Alzheimer’s disease. This suggests that estradiol therapy may have long-term effects on the brain.”

More research is being conducted at eight KEEPS sites to further explore the risks and benefits of menopausal HT as it relates to preventing Alzheimer’s disease (n = 688, mean age, 65 years). The study is scheduled to run through 2023.

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