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17ß-Estradiol Reduces Plasma Aß40 for HRT-Naïve Postmenopausal Women With Alzheimer Disease

A Preliminary Study

Received September 5, 2002; revised November 12, November 22, November 26, 2002; accepted November 26, 2002. From the Geriatric Research, Education, and Clinical Center (GRECC; LDB,SC,MAR,SRP), the VA Puget Sound Health Care System, Seattle/Tacoma, WA, Depts. of Psychiatry and Behavioral Sciences (LDB,SC,MC,MAR), and Medicine (SRP), the University of Washington School of Medicine, Seattle, WA, Dept. of Pharmacology (KS), the Mayo Clinic, Jacksonville, FL, Dept. of Obstetrics and Gynecology (FZS), the University of Southern California, Los Angeles, CA, Dept. of Medicine (SA), the University of Wisconsin Medical School, Madison, WI, and GRECC, William S. Middleton Veterans Affairs Hospital, Madison, WI (SA). Address correspondence to Dr. Sanjay Asthana, Dept. of Medicine, University of Wisconsin Medical School, 2870 University Ave., Suite 100, Madison, WI 53705.

OBJECTIVE: One mechanism to support the potentially beneficial effects of estrogen in the brain for postmenopausal women potentially involves the hormone's ability to favorably alter the processing of amyloid-precursor protein (APP), believed to play an important role in the pathobiology of Alzheimer disease (AD). The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Aß40, for postmenopausal women with AD. METHODS: In a placebo-controlled, double blind, parallel-group design study, 20 women were randomized to receive either 0.10 mg/day of transdermal 17ß-estradiol or a placebo for 8 weeks and were retrospectively evaluated as to whether basal levels of Aß40 were affected by pre-study use of hormone replacement therapy (HRT). Blood samples were collected and cognitive tests were administered at baseline; at Weeks 3, 5, and 8 during treatment; and again 8 weeks after treatment termination. RESULTS: For the group as a whole, plasma Aß40 was not reliably reduced in response to short-term estradiol administration. For HRT-naïve subjects, baseline Aß40 concentrations were higher than those of previous HRT users, and controlled estradiol administration significantly reduced plasma Aß40 by the end of the 8-week treatment period. CONCLUSIONS: These results provide preliminary clinical evidence to support an effect of estradiol on Aß-processing for AD women who are HRT-naïve. This finding suggests that the hormone may serve as an Aß-lowering agent for HRT-naïve AD women, which may, in turn, have ultimate ramifications for the progression of AD pathology.

Key Words: Hormone Therapies • Alzheimer Disease Treatment

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