Matching Items (5)

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The Importance of Studying Interactions With Ovarian Hormones: Implications for Depressive Symptoms in Premenopausal and Menopausal Women

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The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

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Date Created
  • 2021-05

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Cognitive efficacy of three bioidentical, endogenously circulating estrogens given as hormone therapy: Extending prior findings and navigating into unchartered territory

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Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment

Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment of cognitive and physiological menopausal and post-menopausal symptoms. The most common estrogen component of hormone therapy, conjugated equine estrogens (CEE; Premarin) contains many estrogens that are not endogenous to the human body, and that may or may not be detrimental to cognition (Campbell and Whitehead, 1977; Engler-Chiurazzi et al., 2011; Acosta et al., 2010). We propose the use of a novel treatment option in the form of a naturally-circulating (bioidentical) estrogen called estriol. Due to estriol’s observed positive effects on synaptic functioning and neuroprotective effects in the hippocampus (Ziehn et al., 2012; Goodman et al., 1996), a brain structure important for spatial learning and memory, estriol is promising as a hormone therapy option that may attenuate menopausal- and age- related memory decline. In the current study, we administered one of the three bioidentical estrogens (17β-Estradiol, 4.0 µg/day; Estrone, 8.0 µg/day; Estriol, 8.0 µg/day) or the vehicle polyethylene glycol by subcutaneous osmotic pump to ovariectomized Fisher-344 rats. We compared these groups to each other using a battery of spatial learning tasks, including the water radial-arm maze (WRAM), Morris water maze (MM), and delayed-match-to-sample maze (DMS). We found that all estrogens impaired performance on the WRAM compared to vehicle, while 17β-estradiol administration improved overnight forgetting performance for the MM. The estriol group showed no cognitive enhancements relative to vehicle; however, there were several factors indicating that both our estriol and estradiol doses were too high, so future studies should investigate whether lower doses of estriol may be beneficial to cognition.

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Created

Date Created
  • 2015-05

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The Gender Differences in Heart Disease and the Cardiovascular Benefits of Estrogen

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Heart disease is the number one killer of men and women in the world. The incidence of cardiovascular disease is known to be much higher in men than women until

Heart disease is the number one killer of men and women in the world. The incidence of cardiovascular disease is known to be much higher in men than women until around the ages of 60-75 years, when the occurrence of the disease becomes approximately equal in both sexes. Additionally, the occurrence of heart disease is significantly lower in premenopausal women than postmenopausal women. Since men have a higher risk for heart disease than women until 10-15 years after the average age of menopause and postmenopausal women have a higher risk of cardiovascular disease than premenopausal women, it is hypothesized that endogenous estrogen exposure throughout the fertile period of a woman's life postpones the onset of cardiovascular disease. Research shows estrogen has beneficial effects on the cardiovascular system by regulating multiple metabolic processes including lipid metabolism, vasodilation, nitric oxide synthesis, cytochrome c apoptosis, and mitochondrial antioxidant production. Though estrogen has been found to have cardiovascular benefits on individual metabolic processes, the treatment of synthetic estrogen on postmenopausal women and men to reduce the overall risk of heart disease is very controversial. The controversy of synthetic estrogen is partially due to the fact that most studies done using estrogen replacement therapy on postmenopausal women and men resulted in either no effects or harmful effects on the cardiovascular system. Hormone replacement therapy has also been associated with a higher risk of multiple medical conditions, especially venous thromboembolism and breast cancer. This review will explore these topics and consider the costs and benefits of estrogen replacement therapy.

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Created

Date Created
  • 2019-05

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On the cognitive impact of endogenous and exogenous hormone exposures across the lifespan

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Women are exposed to numerous endogenous and exogenous hormones across the lifespan. In the last several decades, the prescription of novel hormonal contraceptives and hormone therapies (HTs) have resulted in

Women are exposed to numerous endogenous and exogenous hormones across the lifespan. In the last several decades, the prescription of novel hormonal contraceptives and hormone therapies (HTs) have resulted in aging women that have a unique hormone exposure history; little is known about the impact of these hormone exposures on short- and long- term brain health. The goal of my dissertation was to understand how lifetime hormone exposures shape the female cognitive phenotype using several innovative approaches, including a new human spatial working memory task, the human radial arm maze (HRAM), and several rodent menopause models with variants of clinically used hormone treatments. Using the HRAM (chapter 2) and established human neuropsychological tests, I determined males outperformed females with high endogenous or exogenous estrogen levels on visuospatial tasks and the spatial working memory HRAM (chapter 3). Evaluating the synthetic estrogen in contraceptives, ethinyl estradiol (EE), I found a high EE dose impaired spatial working memory in ovariectomized (Ovx) rats, medium and high EE doses reduced choline-acetyltransferace-immunoreactive neuron population estimates in the basal forebrain following Ovx (chapter 4), and low EE impaired spatial cognition in ovary-intact rats (chapter 5). Assessing the impact of several clinically-used HTs, I identified a window of opportunity around ovarian follicular depletion outside of which the HT conjugated equine estrogens (CEE) was detrimental to spatial memory (chapter 6), as well as therapeutic potentials for synthetic contraceptive hormones (chapter 9) and bioidentical estradiol (chapter 7) during and after the transition to menopause. Chapter 6 and 7 findings, that estradiol and Ovx benefitted cognition after the menopause transition, but CEE did not, are perhaps due to the negative impact of ovarian-produced, androstenedione-derived estrone; indeed, blocking androstenedione’s conversion to estrone prevented its cognitive impairments (chapter 8). Finally, I determined that EE combined with the popular progestin levonorgestrel benefited spatial memory during the transition to menopause, a profile not seen with estradiol, levonorgestrel, or EE alone (chapter 9). This work identifies several cognitively safe, and enhancing, hormonal treatment options at different time points throughout female aging, revealing promising avenues toward optimizing female health.

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Created

Date Created
  • 2015

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Comprehensive Analysis of Volatile Biomarkers for Female Fertility

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One out of ten women has a difficult time getting or staying pregnant in the United States. Recent studies have identified aging as one of the key factors attributed to

One out of ten women has a difficult time getting or staying pregnant in the United States. Recent studies have identified aging as one of the key factors attributed to a decline in female reproductive health. Existing fertility diagnostic methods do not allow for the non-invasive monitoring of hormone levels across time. In recent years, olfactory sensing has emerged as a promising diagnostic tool for its potential for real-time, non-invasive monitoring. This technology has been proven promising in the areas of oncology, diabetes, and neurological disorders. Little work, however, has addressed the use of olfactory sensing with respect to female fertility. In this work, we perform a study on ten healthy female subjects to determine the volatile signature in biological samples across 28 days, correlating to fertility hormones. Volatile organic compounds (VOCs) present in the air above the biological sample, or headspace, were collected by solid phase microextraction (SPME), using a 50/30 µm divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) coated fiber. Samples were analyzed, using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). A regression model was used to identify key analytes, corresponding to the fertility hormones estrogen and progesterone. Results indicate shifts in volatile signatures in biological samples across the 28 days, relevant to hormonal changes. Further work includes evaluating metabolic changes in volatile hormone expression as an early indicator of declining fertility, so women may one day be able to monitor their reproductive health in real-time as they age.

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Created

Date Created
  • 2018