Matching Items (3)
Description
The objective of this study was to examine the potential effects of long term hormone replacement therapy on cardiovascular autonomic nervous system responses to laboratory social stressors. The participants were 38 postmenopausal women, 18 using estrogen and progesterone hormone replacement therapy for at least 2 years and 20 control participants without hormone replacement therapy. All women completed orthostasis (standing and sitting), then speech and math tasks (speech and math were counterbalanced). Cardiovascular measures of sympathetic nervous system (pre-ejection period, PEP) and parasympathetic nervous system (respiratory sinus arrhythmia, RSA) along with heart rate were collected throughout all periods (baseline, orthostasis, and stressors). For orthostasis, results of mixed analyses of variance (ANOVAs) showed expected period effects for heart rate, RSA and PEP, but no group or group by period interaction was significant. For the psychological stressors, period main effects were significant for all three variables, suggesting that the tasks were effective at inducing stress. Also, there was a significant interaction between group and period for RSA, demonstrated by greater decrease during the psychological stressor period in the group using HRT. The interactions between group and period for heart rate and PEP were non-significant. These findings support the notion that HRT may slow age-related decreases in parasympathetic responsiveness. Furthermore, changes in vagal reactivity in relation to use of HRT appear to occur within mechanisms involving response and coping with psychological stressors, rather than mechanisms that accommodate basic physiological task such as orthostasis.
ContributorsValancova-Acevedo, Katarina (Author) / Burleson, Mary H. (Thesis advisor) / Roberts, Nicole A. (Committee member) / Newman, Matt L. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
Description
Progestogens, such as progesterone (P4), medroxyprogesterone acetate (MPA), and micronized progesterone (mP4), are given to ovary-intact women during the transition to menopause to attenuate heavy uterine bleeding and other symptoms. Both progesterone and MPA administration have been shown to impair cognition in ovariectomized (Ovx) rats compared to vehicle-treated controls. mP4, however, has yet to be investigated for cognitive effects in a preclinical setting. Further, progestogens affect the GABA (-aminobutyric acid) ergic system, specifically glutamic acid decarboxylase (GAD) the rate limiting enzyme necessary for synthesizing GABA. The goal of this experiment was to investigate the cognitive impact of P4, MPA, and mP4, in an ovary-intact transitional menopause model using 4-vinylcyclohexene diepoxide (VCD) and assess whether these potential changes were related to the GABAergic system. One group of rats received vehicle injections, and the remainder of the groups received VCD to induce follicular depletion, modeling transitional menopause in women. Vehicle or hormone administration began during perimenopause to model the time period when women often take progestogens alone. Rats then underwent testing to assess spatial working and reference memory in the water radial-arm maze (WRAM) and spatial reference memory in the Morris water maze (MWM). Results indicate that P4 and MPA improved learning for working memory measure, but only MPA impaired memory retention in the WRAM. For the WRAM reference memory measure, VCD only treated rats showed impaired learning and memory retention compared to vehicle controls; progestogens did not impact this impairment. Although GAD expression did not differ between treatment groups, in general, there was a relationship between GAD expression and WRAM performance such that rats that tended to have higher GAD levels also tended to make more WRAM working memory errors. Thus, while P4 and MPA have been previously shown to impair cognition in an Ovx model, giving these hormones early in an ovary-intact perimenopause model elicits divergent effects, such that these progestogens can improve cognition. Additionally, these findings suggest that the cognitive changes seen herein are related to the interaction between progestogens and the GABAergic system. Further investigation into progestogens is warranted to fully understand their impact on cognition given the importance of utilizing progestogens in the clinic.
ContributorsPena, Veronica Leigh (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Conrad, Cheryl (Committee member) / Gipson-Reichardt, Cassandra (Committee member) / Arizona State University (Publisher)
Created2019