Multiple clinically relevant hormone therapy regimens fail to improve cognitive function in aged ovariectomized rhesus monkeys |
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Authors: | Mark G. Baxter Mary T. Roberts Nancy A. Gee Bill L. Lasley John H. Morrison Peter R. Rapp |
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Affiliation: | 1. Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA;2. California National Primate Research Center, Davis, CA, USA;3. Department of Population Health and Reproduction, Center for Health and the Environment, School of Veterinary Medicine, University of California, Davis, CA, USA;4. Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, MD, USA |
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Abstract: | Preclinical studies in aged, surgically-menopausal rhesus monkeys have revealed powerful benefits of intermittent estrogen injections on prefrontal cortex–dependent working memory, together with corresponding effects on dendritic spine morphology in the prefrontal cortex. This contrasts with the inconsistent effects of hormone therapy (HT) reported in clinical studies in women. Factors contributing to this discrepancy could include differences in the formulation and sequence of HT regimens, resulting in different neurobiological outcomes. The current study evaluated, in aging surgically menopausal rhesus monkeys, the cognitive effects of 4 HT regimens modeled directly on human clinical practice, including continuous estrogen treatment opposed by progesterone. None of the regimens tested produced any cognitive effect, despite yielding physiologically relevant serum hormone levels, as intended. These findings have implications for the design of regimens that might optimize the benefits of hormone treatment for healthy aging, and suggest that common HT protocols used by women may fail to result in substantial cognitive benefit, at least via direct effects on the prefrontal cortex. |
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Keywords: | Ovarian hormones Aging Macaque Learning Memory Prefrontal Temporal |
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