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    Can HRT help prevent Alzheimer’s?


    Results from a small pilot study suggest that transdermal estradiol, given to appropriate women in early postmenopause, may help prevent Alzheimer’s disease. Published in The Journal of Alzheimer’s Disease, the findings may have important clinical implications but require confirmation in a larger sample.

    For the Kronos Early Estrogen Prevention Study, investigators randomized 118 women 5 to 36 months past menopause to 0.45 mg/day of oral conjugated equine estrogens (CEE), 50 µg/day of transdermal 17β-estradiol, or placebo pills and patch for 4 years. The women in the treatment arms also received 200 mg/day of oral progesterone for 12 days each month.  All of the participants were cognitively normal and were genotyped for APOE e4, a gene associated with an increased risk of late-onset Alzheimer’s disease.

    Approximately 7 years after randomization and 3 years after the randomized treatment was stopped, deposition of amyloid-β (Aβ), which has been strongly implicated in development of Alzheimer’s disease, was measured in the brains of 68 of the participants. C Pittsburgh compound B (PiB) PET imaging was used and PiB Standard unit value ratios (SUVRs) were calculated.

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    The investigators found that in the APOE e4 carriers, treatment with transdermal 17β-estradiol (n=10) was associated with lower PiB SUVRs than was placebo (n=5) (odds ratio 0.04 [0.004-0.44]) or oral CEE (n=3) (odds ratio 0.01 [0.0006-0.23]) after adjusting for age. No association was seen between PiB SUVRs and hormone therapy in women who did not carry APOE e4.

    “The association of transdermal 17β-estradiol therapy in recently menopausal women with lower Aβ deposition,” the authors said, “has the potential to change the concepts for preventive interventions that drive the field.” Clinical trials are underway in cognitively normal individuals with high PiB retention and in APOE e4 carriers.

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    Judith M. Orvos, ELS
    Judith M. Orvos, ELS, is a a BELS-certified medical writer and editor and an editorial consultant for Contemporary OB/GYN.


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