Loss of olfactory function in later life is common, and decreased smell ability appears to be the first sign of Alzheimer's disease (AD). Recent studies suggest that estrogen replacement therapy (ERT) may lessen or retard the development of postmenopausal declines in cognitive function in healthy older women, as well as older women with AD. The question arises as to whether ERT also protects against postmenopausal olfactory loss. Two lines of circumstantial evidence suggest this may be the case. First, postmenopausal women presenting to the University of Pennsylvania Smell & Taste Center with complaints of chemosensory dysfunction are less likely to be taking Premarin or other estrogens prior to symptom onset than what would be expected from the population at large. Second, ovariectomized rats receiving estradiol have less olfactory loss, and recover more rapidly, from systemic administration of 3-methylindole, an olfactory system neurotoxin. The proposed study will establish whether ERT mitigates olfactory loss observed in postmenopausal women. Employing a paradigm that has been proved powerful in other contexts (e.g., the Baltimore Longitudinal Study of Aging), the investigators will determine whether associations exist between ERT and well-validated measures of both olfactory and cognitive function in 600 women whose estrogen-taking histories are well-defined. If estrogen use is associated in a systematic manner with olfactory function, as they believe will be the case, this study will be important for several reasons. First, it would lead to improving the quality of life for many aging women, since olfaction plays a key role in eating and drinking. Second, it would lead to the reduction of risks associated with olfactory loss such as malnutrition and accidental gas poisonings. Third, it would lead to testable hypotheses regarding the role of reproductive hormones, and their underlying mechanisms, in the maintenance of normal olfactory function.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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Special Emphasis Panel (ZRG1-IFCN-4 (01))
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Finkelstein, Judith A
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University of Pennsylvania
Schools of Medicine
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Doty, Richard L; Tourbier, Isabelle; Ng, Victoria et al. (2015) Influences of hormone replacement therapy on olfactory and cognitive function in postmenopausal women. Neurobiol Aging 36:2053-9
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Doty, Richard L; Cameron, E Leslie (2009) Sex differences and reproductive hormone influences on human odor perception. Physiol Behav 97:213-28
Doty, Richard L; Kisat, Mehreen; Tourbier, Isabelle (2008) Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test. Brain Res 1214:35-9
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Antunes, Marcelo B; Bowler, Rosemarie; Doty, Richard L (2007) San Francisco/Oakland Bay Bridge Welder Study: olfactory function. Neurology 69:1278-84
Mishra, Anupam; Saito, Kenji; Barbash, Scott E et al. (2006) Olfactory dysfunction in leprosy. Laryngoscope 116:413-6

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