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: 10477353
• 负责人: Chrisandra Lee Shufelt
• 金额: $ 73.54万
• 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 2022-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477353
• 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）发生在育龄期并导致排卵功能障碍， 不排卵和不孕可能会持续数月至数年。HA 有多种表型。 包括心理社会压力、焦虑、高水平的体力活动和/或体重减轻的不同组合。 大量人口研究，包括最初的护士健康研究，都与月经周期相关 不规律/闭经与心血管疾病（CVD）事件的关系然而，这些分析并未发现。 将 HA 表型与多囊卵巢综合征 (PCOS) 和其他患病率较低的月经症区分开来 我们小组的最新数据表明，三分之一患有 HA 的女性（平均年龄 27 岁）患有这种疾病。 临床前 CVD 通过无创测量为血管功能障碍，循环细胞因子模式指示 与未接受激素治疗的年龄匹配的月经正常对照相比，血管炎症。 我们提出的研究申请是对资助机会公告 PA-20-281“生育力 作为整体健康指标的状态”，并将研究与心血管相关的生育状态指标 HA 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进行调查。 与临床前 CVD（目标 1a）和血管炎症（目标 1b）相关的 HA 特定表型。 将目标 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 对绝经前几年患有 HA 的女性进行表型分析，并确定与随后 30 年的关联 了解与 CVD 相关的 HA 表型至关重要。 下一步是识别高危女性，以便尽早采取预防措施并改善整体心血管疾病健康状况。 识别年轻的高危女性提供了一个独特的机会，可以在发生心血管疾病时进行早期干预 此外，临床前 CVD 是一种未经治疗的多器官疾病。 可表现为有助于健康的神经认知障碍、外周心血管疾病和慢性肾脏疾病 拟议研究的结果将利用 HA 来识别有 CVD 风险的年轻女性。 表型分析可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 使用现有和新兴的心血管预防措施来解决年轻女性的心血管疾病流行问题 策略。