Scottsdale, AZ—Some postmenopausal hormone therapies appear to affect structural brain changes related to aging, according to a new study.

A report in Menopause notes that sex hormones influence the structure and function of the brain, but less information is available on how hormone therapies affect the brain during menopause.

Mayo Clinic Arizona–led researchers report that their study demonstrates smaller increases in structural brain changes related to aging with hormone-level changes from transdermal estradiol or oral conjugated equine estrogen. 

The study team notes that the structural changes can be seen through magnetic resonance imaging as white matter hyperintensities (WMH), suggesting the changes in brain structure and in cognitive function could be partly related to lower estrogen levels resulting from menopause.

The new study involved participants from the Kronos Early Estrogen Prevention Study, with researchers focused on the link between the changes in hormone levels—from both the brain and the ovary—with different hormone-therapy formulations, as well as structural changes in the brain associated with aging compared with placebo. 

For the research, 78 women adherent to treatment underwent brain magnetic resonance imaging and blood collection before and after 48 months of randomization to 0.45 mg/d oral conjugated equine estrogen (oCEE) daily, 50 μg/d transdermal 17beta estradiol (tE2), or placebo pills and patches. Women in the active treatment groups also received oral 200 mg/d micronized progesterone the first 12 days of the month. 

Researchers measured estradiol (E2), estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum by high-sensitivity liquid chromatography/mass spectrometry at baseline and following 48 months of HT.

Results indicate that serum levels of FSH, LH, E1, or E2 did not associate with WMH volume at baseline. After 48 months of treatment, the study notes smaller increases in white matter hyperintensities associated with decreases in FSH from baseline in the tE2 group and increases in E1 in both tE2 and oCEE groups. Changes in LH did not associate with changes in WMH in any group, however.

In effect, researchers found that smaller increases in age-related structural brain changes were linked to decreases in follicle-stimulating hormone in women taking transdermal estradiol and higher levels of estrone in women in both transdermal estradiol and oral conjugated equine estrogens groups.

“Circulating levels of pituitary-ovarian hormones associate with changes in WMH volume in recently menopausal women using HT,” the authors write. “Whether these relationships would be influenced by different doses of tE2 or oCEE remains to be determined.”

The authors posit that the differences might be related to how hormone therapy is metabolized; they explain that, although an oral administration is further metabolized in the liver, the transdermal hormones are absorbed directly into the peripheral circulation before being metabolized in the liver. 
 
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