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To the Editor: The study by Ms Rosario and colleagues¹ shows a close association between Alzheimer disease (AD) and reproductive hormone levels. The finding that there were no differences in brain estrogen levels brings into question the long-standing hypothesis that men are less susceptible to AD because they continue to produce estrogen from androstenedione, a precursor of testosterone. While the sex steroids are undoubtedly important for brain function, they are controlled by a complex feedback loop that is made up of numerous other hormones including gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, inhibins, activins, and follistatin. Since there is an inverse relationship between serum concentrations of sex steroids and gonadotropins, effects ascribed to declines in estrogen or testosterone could equally well be a consequence of higher levels of gonadotropins. We previously reported that individuals with AD have increased luteinizing hormone in neurons susceptible to AD pathology,² consistent with the current finding . . . [Full Text of this Article]

Richard L. Bowen, MD
Voyager Pharmaceutical Corporation
Raleigh, NC

Ralph N. Martins, PhD
The Sir James McCusker Alzheimer’s Disease Research Unit
Hollywood Private Hospital Centre for Aging and Alzheimer’s Disease
Nedlands, Western Australia

Christopher W. Gregory, PhD
Voyager Pharmaceutical Corporation

Mark A. Smith, PhD; Craig S. Atwood, PhD
csa@medicine.wisc.edu
Institute of Pathology
Case Western Reserve University
Cleveland, Ohio

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