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: 10669706
• 负责人: Chrisandra Lee Shufelt
• 金额: $ 68.77万
• 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/10669706
• 关键词: Address; Adrenal Gland Hyperfunction; Age; Amenorrhea; Anovulation; Anxiety; Biological Markers; Blood Vessels; Body Weight decreased; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Chronic Kidney Failure; Clinical; Complex; Coronary Angiography; Coronary Arteriosclerosis; Coronary heart disease; Data; Development; Diet Records; Disease; Disease Progression; Early identification; Energy Intake; Epidemic; Evaluation; Event; Fertility; Funding; Funding Opportunities; Future; Glucose; Goals; Health; Health Personnel; Hormones; Hypothalamic structure; Hypothyroidism; Infertility; Inflammation; Intervention Trial; Ischemia; Left; Leptin; Life; Longevity; Low Prevalence; Measures; Mediating; Menstrual cycle; Menstruation Disturbances; Monitor; Myocardial Infarction; National Heart, Lung, and Blood Institute; Neurosecretory Systems; Nurses' Health Study; Organ; Outcome; Patient Outcomes Assessments; Patients; Pattern; Peripheral; Phenotype; Physical activity; Polycystic Ovary Syndrome; Population; Population Study; Premenopause; Prevention strategy; Preventive; Preventive care; Prospective, cohort study; Psychosocial Stress; Questionnaires; Registries; Reporting; Reproductive Endocrinology; Reproductive system; Research; Risk; Risk Factors; Stroke; Syndrome; Translating; Vascular Diseases; Woman; Women' s Health; adjudication; cardiovascular disorder risk; cardiovascular health; clinical care; cohort; cytokine; design; direct application; fitbit; follow-up; health disparity; hormone therapy; improved; indexing; innovation; multidisciplinary; neurocognitive disorder; nutrition; ovarian dysfunction; pre-clinical; premature; reactive hyperemia; recruit; remote patient monitoring; reproductive; vascular inflammation; young woman

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.

摘要/摘要 下丘脑闭经(HA)发生在生殖年龄段，导致排卵功能障碍， 无排卵和不孕症，可延长数月至数年。有多种HA表型 包括心理社会压力、焦虑、高水平的体力活动和/或减肥的不同组合。 大量人群研究，包括最初的护士健康研究，都与月经周期有关 不规律/闭经与心血管疾病(CVD)事件。然而，这些分析并没有 HA表型与多囊卵巢综合征(PCOS)及其他低发生率月经的鉴别 精神错乱。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无创测量为血管功能障碍，循环细胞因子模式表明 血管炎症与未接受激素治疗的年龄匹配的正常月经对照组比较。 我们建议的研究申请响应了资助机会公告PA-20-281 作为整体健康标志的状况“，并将研究生育状况的标志HA与心血管的关系 健康。在目标1中，我们将使用创新的远程患者监控和患者报告的结果来调查 HA特异性表型(S)与临床前心血管疾病(目标1a)和血管炎症(目标1b)相关。到时候我们会的 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，现在可以 绝经前HA患者的表型及其与绝经后30年的相关性 心血管事件危险因素和临床心血管事件。了解与心血管疾病相关的HA表型(S)是至关重要的 下一步是确定处于危险中的妇女，以便采取预防行动，改善整体心血管疾病健康状况。早些时候 识别年轻的高危女性提供了一个独特的机会，可以在CVD发生时进行早期干预 预防性的方法是最有益的。此外，临床前脑血管病是一种未得到治疗的多器官疾病。 可表现为神经认知障碍、外周性心血管疾病和有助于健康的慢性肾脏疾病 女性之间的不平等。拟议的研究结果将使用HA确定有心血管疾病风险的年轻女性 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 使用现有和新出现的心血管预防措施解决年轻女性中的心血管疾病流行问题 战略。