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Leon J. Thal, MD; Ronald G. Thomas, PhD; Ruth Mulnard, RN, DNSc; Mary Sano, PhD; Michael Grundman, MD, MPH; Lon Schneider, MD

Arch Neurol. 2003;60:209-212.

Objective  To investigate whether an association exists between estradiol and estrone levels and measures of cognitive functioning in women with Alzheimer disease (AD) treated with conjugated equine estrogen (Premarin; Wyeth-Ayerst, Philadelphia, Pa).

Methods  We studied 120 postmenopausal women who underwent hysterectomy and who had AD treated with Premarin for 1 year. Plasma estradiol and estrone levels were determined at multiple points during the 1-year treatment trial. The change from baseline level at 2 and 12 months was associated with the change score on 7 different assessments of cognitive functioning.

Results  At baseline, estradiol levels were low and there were no associations between the estradiol level and the 7 neuropsychological measures. A similar pattern was observed for estrone treatment. During treatment with 0.625 mg/d of Premarin, estradiol levels increased about 4-fold; while receiving 1.25 mg/d of Premarin, estradiol levels increased about 8-fold. A similar pattern was seen with estrone treatment. For both estradiol and estrone levels, there were no significant associations between the change in plasma level and the change in neuropsychological test scores at either 2 or 12 months.

Conclusion  Although Premarin elevated estradiol and estrone levels, there was no association between hormone levels and cognitive functioning after either 2 or 12 months of treatment.

From the Departments of Neurosciences (Drs Thal and Grundman) and Family and Preventive Medicine (Dr Thomas), University of California, San Diego, School of Medicine, La Jolla; Veterans Affairs San Diego Healthcare System, San Diego, Calif (Dr Thal); Institute for Brain Aging and Dementia, University of California, Irvine (Dr Mulnard); Sergievsky Center, Columbia University, New York, NY (Dr Sano); and the Departments of Psychiatry and Neurology, Keck School of Medicine, University of Southern California, Los Angeles (Dr Schneider).

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