Hypothalamic Amenorrhea as a Fertility Status Marker for Cardiovascular Health

下丘脑闭经作为心血管健康的生育状态标志

• 批准号: 10704785
• 负责人: Chrisandra Lee Shufelt
• 金额: $ 73.54万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10704785
• 关键词: Hypothalamic; Amenorrhea; Fertility; Status; Marker

SUMMARY/ABSTRACT Hypothalamic amenorrhea (HA) occurs during reproductive years and results in ovulatory dysfunction, anovulation and infertility which can be prolonged from months to years. There are multiple HA phenotypes including varying combinations of psychosocial stress, anxiety, high levels of physical activity and/or weight loss. Large population studies, including the original Nurses’ Health Study have related menstrual cycle irregularity/amenorrhea with cardiovascular disease (CVD) events. However, these analyses have not differentiated the HA phenotype from polycystic ovary syndrome (PCOS) and other lower prevalence menstrual disorders. Emerging data from our group indicates that one-third of women with HA (mean age 27 yrs) have preclinical CVD measured noninvasively as vascular dysfunction, and circulating cytokine patterns indicative of vascular inflammation compared to age-matched eumenorrheic controls not on hormone therapy. Our proposed research application responds to the funding opportunity announcement PA-20-281, “Fertility Status as a Marker for Overall Health” and will study HA, a marker of fertility status, related to cardiovascular health. In Aim 1, we will use innovative remote patient monitoring and patient reported outcomes to investigate HA specific phenotype(s) related to preclinical CVD (Aim 1a) and vascular inflammation (Aim 1b). We will then expand our analysis in Aim 2 to the Nurses’ Health Study II, a large prospective cohort study that can now phenotype women with HA in the premenopausal years and determine associations with subsequent 30 year incident CVD risk factors and clinical CVD events. Understanding the HA phenotype(s) related to CVD is a crucial next step to identify women at-risk in order to take preventive action and improve overall CVD health. Early identification of young at-risk women presents a unique opportunity to intervene earlier in life when CVD preventive approaches are most beneficial. Further, preclinical CVD is a multi-organ disease that left untreated can manifest in neurocognitive disorders, peripheral CVD, and chronic kidney disease that contribute to health disparities in women. The outcome of the proposed research will identify young women at risk of CVD using HA phenotyping to inform the design of next step intervention trials and, ultimately, to translate our findings to clinical care to address the CVD epidemic in younger women using existing and emerging cardiovascular preventive strategies.

总结/摘要 下丘脑性闭经（HA）发生在生育年龄，并导致排卵功能障碍， 不排卵和不孕症，可延长数月至数年。存在多种HA表型 包括心理社会压力、焦虑、高水平的身体活动和/或体重减轻的不同组合。 大规模人群研究，包括最初的护士健康研究， 不规则/闭经伴心血管疾病（CVD）事件。然而，这些分析并没有 将HA表型与多囊卵巢综合征（PCOS）和其他低患病率的月经失调症相区分， 紊乱来自我们小组的新数据表明，三分之一的HA女性（平均年龄27岁） 临床前CVD以无创方式测量为血管功能障碍，循环细胞因子模式表明 与年龄匹配的未接受激素治疗的对照组相比， 我们提出的研究申请响应了资助机会公告PA-20-281，“生育率” 作为整体健康标志的状态”，并将研究与心血管疾病相关的生育状态标志HA， 健康在目标1中，我们将使用创新的远程患者监测和患者报告的结果来调查 与临床前CVD（目的1a）和血管炎症（目的1b）相关的HA特异性表型。然后我们将 将我们在目标2中的分析扩展到护士健康研究II，这是一项大型前瞻性队列研究， 表型妇女与HA在绝经前的年，并确定与随后的30年 事件CVD危险因素和临床CVD事件。了解与CVD相关的HA表型是一个关键 下一步是确定有风险的妇女，以便采取预防措施，改善心血管疾病的整体健康状况。早期 识别年轻的高危女性提供了一个独特的机会，在生命的早期干预， 预防措施最为有益。此外，临床前CVD是一种未治疗的多器官疾病 可表现为神经认知障碍、外周CVD和慢性肾脏疾病， 妇女的不平等。拟议的研究结果将确定年轻妇女在心血管疾病的风险使用HA 表型分析为下一步干预试验的设计提供信息，并最终将我们的发现转化为临床研究。 使用现有和新出现的心血管预防药物治疗年轻女性心血管疾病流行 战略布局