[Frontiers in Bioscience E4, 976-997, January 1, 2012]

Sex hormones, aging, and Alzheimer's disease

Anna M. Barron1,2, Christian J. Pike1

1USC Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089 USA, 2Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 153-8902 Japan


1. Abstract
2. Introduction
2.1. Aging and loss of sex hormones
2.2. Age-related sex hormone loss and AD risk
3. Sex hormones reduce beta-amyloid levels
3.1. Sex hormones regulate beta-amyloid production
3.2. Sex hormones regulate beta-amyloid clearance
4. Progesterone: The other sex hormone
5. Hormone therapy & AD
5.1. Hormone therapy & the aging brain
5.2. SERMS & SARMS: Alternatives to conventional hormone therapies
6. Perspective
7. Acknowledgements
8. References


A promising strategy to delay and perhaps prevent Alzheimer's disease (AD) is to identify the age-related changes that put the brain at risk for the disease. A significant normal age change known to result in tissue-specific dysfunction is the depletion of sex hormones. In women, menopause results in a relatively rapid loss of estradiol and progesterone. In men, aging is associated with a comparatively gradual yet significant decrease in testosterone. We review a broad literature that indicates age-related losses of estrogens in women and testosterone in men are risk factors for AD. Both estrogens and androgens exert a wide range of protective actions that improve multiple aspects of neural health, suggesting that hormone therapies have the potential to combat AD pathogenesis. However, translation of experimental findings into effective therapies has proven challenging. One emerging treatment option is the development of novel hormone mimetics termed selective estrogen and androgen receptor modulators. Continued research of sex hormones and their roles in the aging brain is expected to yield valuable approaches to reducing the risk of AD.