Sex-differences in cardiometabolic physiology are evident; however, the inclusion of female participants in research studies for the purposes of exploration of sex-specific physiological responses is limited by the perceived complexity due to hormonal cycles. This dissertation examined the prevalence of sex-specific inclusion in human vascular exercise physiology research, investigate the influence of endogenous and exogenous sex hormones on cardiovascular, respiratory, and skeletal muscle metabolism, and consider sex- and gender-differences in peripheral vascular outcomes. The first study confirmed a sex-specific bias towards male inclusion in vascular exercise physiology research, with perceived hormonal complexity noted as one rationale for sex-specific exclusion. To address this perception, we reviewed the literature and identified a small effect of the menstrual cycle, and a more robust influence of oral contraceptive pills, on macrovascular endothelial function, with no influence on smooth muscle function or arterial stiffness. Our next set of studies objectively evaluated the influence of the natural menstrual and two generations of oral contraceptive pills on a comprehensive suite of cardiovascular, respiratory, and metabolic outcomes, and found largely no influence on these outcomes or the underlying vascular cellular regulation, apart from a small effect elevated endogenous and exogenous sex hormones on brachial artery endothelial function. Another area identified in our initial sex-inclusion review was the absence of gender-based research in vascular exercise physiology. Our final study found that biological sex aligned with gender identity, but not gender expression and influenced cardiovascular markers by including elevating systolic blood pressure, central arterial stiffness and endothelial function in males and men compared to females and women. Altogether, this dissertation provides substantial evidence for the lack of hormonal cycle influence of endogenous and exogenous sex hormones on three organ systems, which will open further incorporating females into research study design. / Dissertation / Doctor of Philosophy (PhD) / Females have been historically understudied in basic science and clinical research. This dissertation set out to explore sex-specific prevalence of research participants in human vascular exercise physiology studies and examined how sex hormones (through the menstrual cycle and oral contraceptive pill use) impact the cardiovascular, respiratory, and skeletal muscle metabolism systems. We found that there is an evident male-bias in vascular exercise physiology research, due in part to the perceived complexity of how sex hormones may impact the cardiovascular system. We also found that the menstrual cycle and oral contraceptive pill cycle have minimal influence on the biological systems examined. While there are evident sex-differences in cardiovascular outcomes, gender expression does not appear to have an impact in young adults. This research is foundational to further the inclusion of female participants in human physiology research and encourage future considerations of how sex/gender may influence physiological outcomes.

abstract: 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. / Dissertation/Thesis / Doctoral Dissertation Psychology 2015

The aim of this diploma thesis was to summarize the topic of the anterior cruciate ligament (LCA) injury dependency on the menstrual cycle phase of young women with regular sport activity. The general part describes basic knowledge about connective tissue, LCA, issues of LCA injury and related risk situations. Large chapter is dedicated to sex hormones and menstrual and ovarian cycle, which is crucial for understanding the whole topic. The main part is focused on impact of sex hormones and hormonal contraception on connective tissue, but also on muscle and nervous tissues, which might be as well important for LCA injury incidence. Next part of the thesis consists of a questionnaire survey. 52 respondents aged 15-35 with rupture or partial rupture of LCA answered the non-standardized questionnaire compiled specially for this thesis and the results were statistically processed. 14 respondents were using hormonal contraception, remaining 38 had physiological menstrual cycle. Based on the theoretical findings we expected highest incidence of LCA injuries among women without contraception in phases of menstrual cycle with highest levels of oestrogen (10th -15th day). That was confirmed (P-value: 0,0218) as well as overall lower incidence among women using contraception (P-value: 0,0006). Expected higher...