Neurobiology of hormonal contraception

项目总结/摘要 在K23资助期间，我将成为一名独立的研究人员，专注于性类固醇的神经影响， 他们的类似物，因为它们与行为过程有关。我的研究旨在提高性腺类固醇 在女性生命周期中的操控作为关键的第一步，本研究计划将评估 激素避孕对大脑奖励处理的影响，并评估其与行为副作用的关系 和患者利用率。激素避孕的行为副作用，如消极情绪和减少 性欲是停药的最常见原因。停用 激素避孕是一个已知的意外怀孕的风险因素。为了个性化治疗， 限制这些副作用以及提高未来药物的耐受性，类固醇神经科学的进展是 必要目前对激素避孕如何影响大脑功能的理解受到限制， 缺乏前瞻性对照研究。利用安慰剂对照设计，该项目将是第一个 阐明含乙炔雌二醇和左炔诺孕酮（EE/LNG）的常用口服避孕药 通过神经成像和行为评估影响大脑奖励功能。这项研究将揭示 EE/LNG如何影响生态相关行为（即，动机，性功能）， 并作为研究其他类固醇避孕药对这些过程的基础。 我在行为神经科学方面的研究背景加上我对女性行为的临床兴趣， 健康最终导致了我目前对心理神经内分泌学的关注。现在，作为一名助理教授， 科罗拉多大学安舒茨医学院（CU-AMC），我有重要的支持和资源来培养 利用K23机制实现独立。我的导师团队由C。Neill Epperson，医学博士和 包括神经影像学专家（Tregellas和Epperson博士），性类固醇（Epperson和Santoro博士）， 统计建模（Sammel博士）。我的培训目标包括加深我对以下方面的理解：1） 性类固醇对神经行为的影响; 2）神经成像的先进技术; 3）临床试验， 统计建模我还将4）提高我的研究合作，写作和演讲技巧，5）获得 在负责任地开展研究方面的额外培训。我将通过以下方式实现这些培训目标： 课程和研讨会，导师/顾问的指导，以及完成拟议的研究。

PROJECT SUMMARY/ABSTRACT During K23 funding, I will become an independent investigator focusing on the neural effects of sex steroids and their analogues as they relate to behavioral processes. My research aims to improve gonadal steroid manipulations across the female lifespan. As a critical first step, this research plan will evaluate the effect of hormonal contraception on reward processing in the brain and assess its relationship to behavioral side effects and patient utilization. Behavioral side effects of hormonal contraception such as negative mood and decreased sexual desire represent some of the most frequently cited reasons for discontinuation. Discontinuation of hormonal contraception is a known risk factor for unintended pregnancies. In order to personalize treatment that limits such side effects as well as improve tolerability of future agents, progress in steroid neuroscience is necessary. Current understanding of how hormonal contraception influences brain function has been limited by a lack of prospective controlled investigations. Utilizing a placebo-controlled design, this project will be the first to elucidate how a common oral contraceptive agent containing ethynyl estradiol and levonorgestrel (EE/LNG) influences brain reward function via both neuroimaging and behavioral assessment. This research will reveal how EE/LNG affects ecologically relevant behaviors (i.e., motivation, sexual function) in reproductive women, and serve as the basis for investigation of other steroid contraceptive agents on these processes. My research background in behavioral neuroscience combined with my clinical interests in women’s behavioral health eventually led to my current focus in psychoneuroendocrinology. Now, as an Assistant Professor at the University of Colorado Anschutz Medical Campus (CU-AMC), I have significant support and resources to train to independence utilizing the K23 mechanism. My mentorship team is led by C. Neill Epperson, M.D. and includes experts in neuroimaging (Drs. Tregellas and Epperson), sex steroids (Drs. Epperson and Santoro), and statistical modeling (Dr. Sammel). My training objectives include deepening my understanding of: 1) neurobehavioral effects of sex steroids; 2) advanced techniques in neuroimaging and 3) clinical trials and statistical modeling. I will also 4) improve my research collaborating, writing and presentation skills and 5) obtain additional training in the responsible conduct of research. I will accomplish these training objectives through coursework and seminars, guidance from mentors/consultants, and completion of the proposed research.