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: 10289995
• 负责人: Chrisandra Lee Shufelt
• 金额: $ 76.66万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 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/10289995
• 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; 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; adjudicate; cardiovascular disorder risk; cardiovascular health; clinical care; cohort; cytokine; design; 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）发生在生殖年中，导致排卵功能障碍， 有多种HA表型 包括社会心理压力，焦虑，高水平的体育活动和/或体重减轻的不同组合。 大型人口研究，包括原始护士的健康研究，具有相关的月经周期 心血管疾病（CVD）事件的不规则性/闭经。但是，这些分析尚未 将HA表型与多囊卵巢综合征（PCOS）和其他较低患病率区分开 疾病。来自我们小组的新兴数据表明，HA（平均年龄27岁）的女性中有三分之一 临床前CVD以血管功能障碍的方式无创测量，并循环细胞因子模式表明 与不匹配雌激素治疗的年龄匹配的Eumenorrheic对照相比，血管炎症。 我们提出的研究申请对资金机会公告PA-20-281的回应，“生育 作为整体健康标记的状态”，并将研究HA，这是生育状态的标志，与心血管有关 健康。在AIM 1中，我们将使用创新的远程患者监控和患者报告的结果进行调查 与临床前CVD（AIM 1A）和血管注射（AIM 1B）有关的HA特异性表型。然后我们会 将我们的AIM 2分析扩展到护士健康研究II，这是一项大型的前瞻性队列研究，现在可以 在绝经前的表型女性，并确定与随后30年的关联 事件CVD风险因素和临床CVD事件。了解与CVD有关的HA表型是至关重要的 下一步确定妇女处于危险中，以采取预防措施并改善整体CVD健康。早期的 年轻的高风险妇女的识别提供了一个独特的机会，可以在CVD时介入较早的生活 预防方法是最有益的。此外，临床前CVD是一种多器官疾病，未经治疗 可以在神经认知疾病，周围CVD和慢性肾脏疾病中表现出来，这有助于健康 女性差异。拟议的研究的结果将确定使用HA有CVD风险的年轻女性 表型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 注意使用现有和新兴心血管预防的年轻女性的CVD流行 策略。