Duration of Hormonal Contraceptive Use: Immune Responses & Vaginal Microbiota

描述(申请人提供)：全世界超过3亿妇女使用某种形式的荷尔蒙避孕(HC)。动物研究表明，性激素对免疫反应的影响取决于暴露时间的长短。人类研究很少关注这个问题。我们对这一建议的总体假设是，HC的使用时间是一个关键的独立因素，有助于HC对粘膜免疫反应和阴道微生物区系的影响。这项建议的目的是：1。建立一个发起HC的预期妇女队列，并对这些妇女进行为期两年的跟踪。2.确定使用HC对阴道微生物群落结构的短期和长期影响。3.明确短期和长期使用HC对阴道、宫颈外和宫颈内促炎和抗炎细胞因子和趋化因子反应的影响。更长期的目标是从这个队列中建立一个标本储存库，使我们能够进一步定义粘膜和全身免疫反应的变化。这项提议是由约翰霍普金斯大学医学院、约翰霍普金斯大学布隆伯格公共卫生学院和马里兰大学基因组科学研究所合作完成的。为这项研究组建的团队包括元基因组学、统计学、免疫学、流行病学、传染病、妇科学和数学生物信息学方面的多学科专业知识，这些都是利用将产生的数据所必需的。毫无疑问，HC在维持健康以及经济和政治稳定方面发挥着重要作用。因此，继续使用它们是至关重要的，也是无可争辩的。了解短期和长期使用外源性类固醇如何影响免疫反应和下生殖器环境，对于确保以最大限度地提高安全性和有效性的方式使用这些药物至关重要。这项研究计划产生的信息应该有助于推动诊断工具的发展，并确定改善妇女健康的新目标。 公共卫生相关性：我们对这一建议的总体假设是，激素避孕(HC)的使用时间是一个关键的独立因素，有助于HC对粘膜免疫反应和阴道微生物区系的影响。全球超过3亿女性使用HC，因此确定哪些女性可能从HC的使用中受益以及哪种类型的HC将提供最大益处将有助于优化女性使用HC。此外，了解性激素是如何影响免疫反应的，将使我们能够探索利用这些因素最大限度地提高对疫苗的粘膜和全身免疫反应的可能性。

DESCRIPTION (provided by applicant): Over 300 million women worldwide use some form of hormonal contraception (HC). Animal studies suggest that effects of sex hormones on immune responses are dependent on the duration of exposure. Human studies have rarely focused on this issue. Our overall hypothesis for this proposal is that the duration of HC use is a critical independent factor that contributes to the effects of HC on mucosal immune responses and the vaginal microbiota. The aims of this proposal are: 1. To establish a prospective cohort of women initiating HC and follow these women for two years. 2. To determine the short-term and longer-term impact of HC use on the structure of the vaginal microbial communities. 3. To define the impact of short term and longer-term HC use on pro-and anti-inflammatory cytokine and chemokine responses in the vagina, ectocervix, and endocervix. The longer-term goal is to establish a specimen repository from this cohort that would allow us to further define changes in mucosal and systemic immune responses. This proposal is a collaboration between Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, and the University of Maryland Institute for Genome Sciences. The team assembled for this study encompasses the multidisciplinary expertise in metagenomics, statistics, immunology, epidemiology, infectious diseases, gynecology, and mathematical bioinformatics necessary to exploit the data that will be generated. There is no doubt that HC play an important role in maintaining health, as well as economic, and political stability. As such, their continued use is vital and incontrovertible. Understanding how the short-term and long-term use of exogenous sex steroids impacts immune responses and the lower genital environment is critical to ensure that these agents are used in a way that maximizes safety and efficacy. The information generated from this research program should help drive the development of diagnostic tools and identify new targets to improve women's health. PUBLIC HEALTH RELEVANCE: Our overall hypothesis for this proposal is that the duration of hormonal contraception (HC) use is a critical independent factor that contributes to the effects of HC on mucosal immune responses and the vaginal microbiota. Over 300 million women worldwide use HC, so knowledge gained from identifying which women are likely to benefit from HC use and the type of HC that would provide the most benefit will help optimize the use of HC in women. Moreover, understanding how sex hormones influence immune responses would allow us to explore the possibility of harnessing these agents to maximize mucosal and systemic immune responses to vaccines.