Cognitive response to estradiol in postmenopausal women is modified by high cortisol
Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA.Neurobiology of aging (Impact Factor: 5.01). 08/2011; 33(4):829.e9-20. DOI: 10.1016/j.neurobiolaging.2011.07.002
Estradiol has potent favorable effects on brain function and behavior in animals while in human trials, the results are inconsistent. A number of potential mediating variables influencing response to estradiol have been proposed to account for this variability, 1 of which includes stress. We conducted a placebo-controlled study to examine joint and independent effects of estradiol and elevated levels of the stress hormone cortisol on cognition and biomarkers of aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56-84 years) received 0.10 mg/dL of transdermal 17β-estradiol (E2) or placebo for 8 weeks. During the last 4 days of the trial, subjects also received 90 mg/day (30 mg 3×/day) of oral hydrocortisone (CORT) to induce stress-level elevations in cortisol, or a matched placebo. The 4 groups thus included placebo (placebo patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone). Eight weeks of E2 increased plasma estradiol by 167%, and 4 days of CORT increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal memory (p = 0.03), working memory (p = 0.02), and selective attention (p = 0.04), and the magnitude of these effects was attenuated for E2+CORT. E2-alone and E2+CORT had opposing effects on plasma levels of the amyloid-β (Aβ) biomarker (Aβ40/42 ratio, p < 0.05), with the more favorable response observed for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted by E2 coadministration. Our findings indicate that cognitive and physiological responses to estradiol are adversely affected by elevated stress hormone levels of cortisol in healthy postmenopausal women.
Article: Stress, Inflammation, and Aging
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ABSTRACT: Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of chronic stress on eating behavior in humans is less understood, but it may be linked to HPA responsivity. The purpose of this study was to investigate the influence of chronic social stress and acute stress reactivity on food choice and food intake. Forty-one women (BMI=25.9±5.1 kg/m(2), age range=41 to 52 years) were subjected to the Trier Social Stress Task or a control task (nature movie) to examine HPA responses to an acute laboratory stressor and then invited to eat from a buffet containing low- and high- calorie "comfort" snacks. Women were also categorized as high chronic stress or low chronic stress based on Wheaton Social Stress Index scores. Women reporting higher chronic stress and exhibiting low cortisol reactivity to the acute stress task consumed significantly more calories from chocolate cake on both stress and control visits. Chronic stress in the low cortisol reactor group was also positively related to total fat mass, regional fat percentage, and stress-induced negative mood. Further, women reporting high chronic stress consumed significantly less vegetables, but only in those aged 45 years and older. Chronic stress in women within the higher age category was positively related to total calories consumed at the buffet, stress-induced negative mood and food craving. Our results suggest an increased risk for stress eating in persons with a specific chronic stress signature and imply that a habit of comfort food may link chronic social stress and acute stress-induced cortisol hyporesponsiveness.
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ABSTRACT: Aging is associated with well-recognized alterations in brain function, some of which are reflected in cognitive decline. While less appreciated, there is also considerable evidence of socioemotional changes later in life, some of which are beneficial. In this review, we examine age-related changes and individual differences in four neuroendocrine systems-cortisol, estrogen, testosterone, and oxytocin-as "difference makers" in these processes. This suite of interrelated hormonal systems actively coordinates regulatory processes in brain and behavior throughout development, and their level and function fluctuate during the aging process. Despite these facts, their specific impact in cognitive and socioemotional aging has received relatively limited study. It is known that chronically elevated levels of the stress hormone cortisol exert neurotoxic effects on the aging brain with negative impacts on cognition and socioemotional functioning. In contrast, the sex hormones estrogen and testosterone appear to have neuroprotective effects in cognitive aging, but may decrease prosociality. Higher levels of the neuropeptide oxytocin benefit socioemotional functioning, but little is known about the effects of oxytocin on cognition or about age-related changes in the oxytocin system. In this paper, we will review the role of these hormones in the context of cognitive and socioemotional aging. In particular, we address the aforementioned gap in the literature by: (1) examining both singular actions and interrelations of these four hormonal systems; (2) exploring their correlations and causal relationships with aspects of cognitive and socioemotional aging; and (3) considering multilevel internal and external influences on these hormone systems within the framework of explanatory pluralism. We conclude with a discussion of promising future research directions.
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