Characterizing the influence of endogenous and exogenous sex steroid hormones in the stress response

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Sex hormones, such as estrogen, progesterone and testosterone have widespread influences on cognition, affective states, and stress reactivity. Indeed, fluctuations of sex hormones across the menstrual cycle correspond to altered brain activity and connectivity, alterations in stress hormones, such as cortisol, and pro-inflammatory cytokines (i.e., signaling molecules released by immune cells). Although there has been a shift in the past 10 years to include females in biological research, sex is most often not the focus of the investigation. As a result, significant gaps remain in our understanding as to how alterations in sex hormones, for example through the menstrual cycle or use of hormonal contraceptives, affects biological stress responses in females. With over 100 million women worldwide using hormone contraceptives there is a pressing need for the systematic examination of the how alterations of sex hormones impact female biology, as these may have significant consequences on cognition, behaviour and well-being. Therefore, the overarching objective of this program of research is to examine the role of sex hormones in biological responses to stressors and the long-term implications of disrupting sex hormones, through hormonal contraceptives. First, we will examine whether sex hormones account for sex differences seen between males and females in response to an acute social stressor in the laboratory. We will further assess how biological responses (e.g., cortisol and cytokine levels), to this laboratory stressor will differ according to menstrual cycle phase, and hormonal contraceptive use. We will similarly explore how sex hormones and hormonal contraceptives map onto gene expression, through a process called epigenetics. Moreover, a 2-year prospective study will allow us to assess the long-term associations of sex hormones, hormonal contraceptives and epigenetic patterns with later cortisol and inflammatory profiles. The current program of research will help reveal the short- and long-term biological implications of sex hormones among young females. Moreover, this research will provide novel insights into the targets of sex hormones by identifying top sites marked by epigenetic changes among naturally cycling females and those using hormonal contraceptives. Importantly, this research will tease-apart the biological consequences of estrogens versus progestin-only hormonal contraceptives. These findings could potentially inform policies regarding recommendations for specific hormonal contraceptives, which could directly impact behaviours, allowing females to make evidence-based decisions as to if, and what type of hormonal contraceptive is best for them.