Neurobiology of hormonal contraception

项目摘要/摘要 在K23基金期间，我将成为一名独立研究员，专注于性类固醇和 它们与行为过程有关的相似之处。我的研究旨在改善性腺类固醇 对女性寿命的操纵。作为关键的第一步，这项研究计划将评估 荷尔蒙避孕对大脑奖赏处理的影响及其与行为副作用的关系 和病人使用率。激素避孕的行为副作用，如消极情绪和情绪下降 性欲是最常被提及的戒烟理由之一。停产 荷尔蒙避孕是意外怀孕的已知风险因素。为了使治疗个性化， 限制此类副作用并提高未来药物的耐受性，类固醇神经科学的进展 这是必要的。目前对荷尔蒙避孕如何影响大脑功能的理解受到以下限制 缺乏前瞻性的受控调查。利用安慰剂对照设计，这个项目将是第一个 阐明一种常用的含乙炔雌二醇和左炔诺孕酮(EE/LNG)的口服避孕药 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如何影响育龄妇女的生态相关行为(即动机、性功能)， 并作为研究其他类固醇避孕药在这些过程中的基础。 我在行为神经科学方面的研究背景，以及我对女性行为的临床兴趣 健康最终导致了我目前对精神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)，我有大量的支持和资源来培训 利用K23机制实现独立。我的导师团队由C.Neill Epson，医学博士和 包括神经成像专家(特雷盖拉斯博士和艾普森博士)、性类固醇专家(艾普森博士和桑托罗博士)以及 统计建模(萨梅尔博士)。我的培训目标包括加深对以下方面的理解：1) 性激素对神经行为的影响；2)神经成像的先进技术；3)临床试验和 统计建模。我还将提高我的研究合作、写作和陈述能力，并获得 负责任的研究行为方面的额外培训。我将通过以下方式实现这些培训目标 课程作业和研讨会，导师/顾问的指导，以及拟议研究的完成。

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.