Investigating the Effects of Sex Hormones on the Female Brain – Necessary Prerequisites and a First Insight on the Influences on Gray Matter Volume

The stereotypic and oversimplified relationship between female sex hormones and undesirable behavior dates back to the earliest days of human society, as already the ancient Greek word for the uterus “hystera” indicated an aversive connection. Remaining and evolving throughout the centuries, transce...

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Bibliographic Details
Main Author: Schuster, Verena
Contributors: Jansen, Andreas (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2020
Online Access:PDF Full Text
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Summary:The stereotypic and oversimplified relationship between female sex hormones and undesirable behavior dates back to the earliest days of human society, as already the ancient Greek word for the uterus “hystera” indicated an aversive connection. Remaining and evolving throughout the centuries, transcending across cultures and various aspects of everyday life, its perception was only recently reframed. Contemporarily, the complex interaction of hormonal phases (i.e., the menstrual cycle), hormonal medication (i.e., oral contraceptives), women’s psychological well-being, and behavior is the subject of multifaceted and more reflected discussions. A driving force of this ongoing paradigm shift was the introduction of this highly interesting and important topic into the realm of scientific research. In particular, this refers to neuroscientific research as it enables a multimodal approach combining aspects of physiology, medicine, and psychology. Here a growing body of literature pointed towards significant alterations of both brain function, such as lateralization of cognitive functions, and structure, such as gray matter concentrations, due to fluctuations and changes in hormonal levels. This especially concerns female sex hormones. However, the more research is conducted within this field, the less reliable these observations and derived insights appear to be. Among other reasons, this is grounded in two particular factors: measurement inconsistencies and diverse hormonal phases accompanied by interindividual differences. The first factor refers to the prominent unreliability of one of the primarily utilized neuroscientific research instruments: functional magnetic resonance imaging (fMRI). This unreliability is seemingly present in paradigms and analyses, as well as their interplay and additionally affected by the second factor. In more detail, hormonal phases and levels apparently further influence neuroscientific results obtained through fMRI as outcomes vary drastically across different cycle phases and medication. This resulting vast uncertainty thus tremendously hinders the further advancement of our understanding of how female sex hormones might alter brain structure and function and, ultimately, behavior. Therefore, precisely controlled study designs need to be assembled and thoroughly validated as a prerequisite for the sufficient and robust research on this exceedingly important and fascinating part of biology. This important endeavor was at the very core of the here presented thesis and aimed to address the outlined concerns through two projects. The first one focused on the unreliability of a multitude of fMRI results, including those studies investigating the lateralization of specific cognitive functions. Additional variability is included by investigating women, as prior research described an influence of sex hormones on the degree of lateralization. The research of the lateralization of various cognitive functions is generally impeded due to a quality discrepancy between paradigms addressing either left- or right-hemispheric functions. Whereas left-dominant functions can be examined with robust and reliable paradigms, equivalents are missing to investigate functions that are lateralized to the right hemisphere, especially visuospatial attention. Accordingly, the thesis’s first project evaluated the robustness of three paradigms for assessing right-hemispheric dominance during visuospatial processing within a repeated measurement design. To this end, reliability and lateralization indices were assessed for each paradigm. The yielded results demonstrated the general utility of the examined paradigms while simultaneously underlining their current limitations concerning reliability and susceptibility to marginal changes of, e.g., measurement parameters. Thus, none of the examined tasks were incorporated into the second project of this thesis, which strived the conceptualization of a comprehensive study design to systematically investigate the effects of female sex hormones on gray and white matter, typically lateralized cognitive functions, and resting state. Women were investigated within a longitudinal study design, and blood samples were collected to determine blood hormone levels. Women with a natural cycle were examined during menstruation, indicated by overall low concentrations of female sex hormones, and midluteal phase, specified by overall high sex hormones levels. Women taking an androgenic effective hormonal contraceptive were investigated during pill-intake and pill-withdrawal, revealing overall low-hormonal values. As structural data is generally less prone to analytical perturbations, and prior studies reported high reliability for volume measures, within this thesis’s extent, the focus was on elucidating the effects on gray matter volume within predefined regions and how these results are influenced by the application of two different analysis pipelines. Overall, descriptively larger gray matter volumes were found within naturally cycling women across pipelines. Distinct brain regions were additionally affected by pill-intake vs. pill-withdrawal within results obtained by only one processing stream. In sum, this thesis’s outcomes highlight the importance of reliable paradigms, comprehensive study designs, and the application of validated analysis pipelines, as indicated by the yielded results differences examining the influence of menstrual cycle phases and oral contraceptive treatment on brain structure. The analysis of the additional acquired functional and structural data obtained within the study will further elucidate the effect of female sex hormones on the brain. Ultimately, this thesis outlines the essential requirements to further investigate and understand the female brain’s underlying physiological and anatomical features that may have motivated ancient greek anatomists to designate the uterus after an outmoded psychiatric condition.
Physical Description:195 Pages