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

性激素，如雌激素、孕激素和睾酮，对认知、情感状态和应激反应有广泛的影响。事实上，性激素在月经周期中的波动对应于大脑活动和连接的变化，应激激素(如皮质醇)和促炎细胞因子(即免疫细胞释放的信号分子)的变化。尽管在过去的10年里，生物研究中出现了将女性包括在内的转变，但性往往不是调查的重点。因此，对于性激素的变化，例如通过月经周期或激素避孕药的使用，如何影响女性的生物应激反应，我们的理解仍然存在重大差距。全世界有1亿多妇女在使用激素避孕药，迫切需要系统地检查性激素的变化如何影响女性的生理，因为这些变化可能会对认知、行为和福祉产生重大影响。因此，这项研究的首要目标是检验性激素在对应激源的生物反应中的作用，以及通过激素避孕扰乱性激素的长期影响。首先，我们将检验性荷尔蒙是否可以解释在实验室中，男性和女性在应对剧烈的社会压力时所看到的性别差异。我们将进一步评估对这种实验室应激源的生物学反应(例如皮质醇和细胞因子水平)将如何根据月经周期阶段和激素避孕用法的不同而不同。类似地，我们将通过一种称为表观遗传学的过程，探索性激素和荷尔蒙避孕药如何映射到基因表达。此外，一项为期两年的前瞻性研究将使我们能够评估性激素、激素避孕药和表观遗传模式与后来的皮质醇和炎症特征的长期关联。目前的研究计划将有助于揭示性激素对年轻女性的短期和长期生物学影响。此外，这项研究将通过确定自然骑自行车的女性和使用激素避孕药的女性的表观遗传变化的顶级位置，为性激素的目标提供新的见解。重要的是，这项研究将梳理雌激素与仅使用黄体酮的激素避孕药的生物学后果。这些发现可能会为有关特定荷尔蒙避孕药的建议的政策提供参考，这可能直接影响行为，使女性能够基于证据做出决定，决定是否以及哪种类型的荷尔蒙避孕药对她们最好。

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.