Androgen-Estrogen Balance in CVD Risk

心血管疾病风险中的雄激素-雌激素平衡

• 批准号: 8847770
• 负责人: Jennifer S Lee
• 金额: $ 33.18万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8847770
• 关键词: Address; Adult; Age; Aging; Androgens; Aromatase; Atherosclerosis; Belief; Binding; Biochemical; Biological Markers; Blood Banks; Cardiovascular Diseases; Carotid Atherosclerotic Disease; Clinical; Complex; Data; Death Rate; Development; Diabetes Mellitus; Elderly; Endocrine; Enzymes; Epidemic; Epidemiology; Equilibrium; Estradiol; Estrogen Therapy; Estrogens; Event; Family Study; Female; Functional disorder; Gender; Globulins; Glucose; Goals; Gonadal Steroid Hormones; Health; Heart; Incidence; Insulin Resistance; Left Ventricular Dysfunction; Life; Longevity; Longitudinal Studies; Measures; Menopause; Minority Groups; Myocardial Infarction; Myocardial dysfunction; Native Americans; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pathway interactions; Population Study; Prediabetes syndrome; Public Health; Relative (related person); Research; Research Personnel; Risk; Risk Factors; Role; Severities; Sex Hormone-Binding Globulin; Staging; Stratification; Testing; Testosterone; Woman; aged; aging population; burden of illness; cardiovascular disorder risk; diabetic; high risk; hormone therapy; male; men; middle age; non-diabetic; prevent; young adult

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is projected to remain the #1 killer this century worldwide. Key CVD risk factors, such as type 2 diabetes and obesity, have reached epidemic proportions, even among younger adults. Sex hormones (such as estrogen and testosterone) are centrally involved in progression to CVD in both men and women. Men are at especially high risk for CVD: male gender confers a 3-fold increased risk of CVD and CVD death rates are shifted 5-10 years earlier in men than in women. The standard explanation for the differing CVD risk invokes differing amounts of endogenous estrogen: greater endogenous estrogen in women, relative to men, provides CV protection until menopause. However, evidence is accumulating that the estrogen explanation is an over-simplification. Our general objective is to identify the roles of the "other" endogenous sex hormones (estrogen in men and androgen in women), in relation to glucose dysregulation, in the development CVD across the adult lifespan. Towards this goal, we propose to relate endogenous sex hormones, glucose dysregulation, and CVD in older adults and relate endogenous sex hormones to atherosclerosis and cardiac dysfunction in younger adults. Our approach centers on two emerging concepts: endogenous sex hormones may assert opposite (or gender-dimorphic) effects in men compared with women and temporal changes, not just levels, of endogenous sex hormones influence CVD risk. We propose to take an efficient, endocrine epidemiological approach. We will use existing data and measure endogenous sex hormones in banked blood already collected repeatedly from Native American men and women within two ongoing longitudinal studies, the Strong Heart Study and the Strong Heart Family Study. Native Americans are a minority group with high rates of CVD and diabetes. Our specific aims are: 1) to differentiate if change in circulating endogenous estrogen, androgen, and SHBG are associated with subsequent CVD events in men and women with diabetes; 2) to determine if levels of circulating endogenous estrogen, androgen, and sex hormone binding globulin (SHBG) levels are associated with subsequent pre-diabetes and diabetes; and 3) across the adult lifespan in men and women, to characterize endogenous androgen and estrogen dynamics and their relationships to carotid atherosclerosis, cardiac dysfunction, and related risk factors, particularly glucose dysregulation and obesity. A better understanding of the interplay of sex hormones and CVD and its risk factors during aging would broadly impact public health strategies, risk stratification, and treatment of CVD.

描述（由申请人提供）：预计心血管疾病 (CVD) 仍将是本世纪全球第一大杀手。关键的 CVD 危险因素，如 2 型糖尿病和肥胖，甚至在年轻人中也已达到流行的程度。性激素（如雌激素和睾酮）在男性和女性的 CVD 进展中起着重要作用。男性患 CVD 的风险特别高：男性患 CVD 的风险增加 3 倍，并且男性的 CVD 死亡率比女性早 5-10 年。 对不同CVD风险的标准解释是内源性雌激素含量不同：相对于男性，女性内源性雌激素含量更高，可以在绝经前提供心血管保护。然而，越来越多的证据表明雌激素的解释过于简单化。 我们的总体目标是确定“其他”内源性激素（男性雌激素和女性雄激素）在成人一生中与血糖失调相关的 CVD 发展中的作用。为了实现这一目标，我们建议将老年人的内源性激素、血糖失调和心血管疾病联系起来，并将内源性激素与年轻人的动脉粥样硬化和心脏功能障碍联系起来。我们的方法集中在两个新兴概念上：与女性相比，内源性激素可能对男性产生相反（或性别二态）的影响，并且内源性激素的时间变化（而不仅仅是水平）影响CVD风险。 我们建议采取有效的内分泌流行病学方法。我们将使用现有数据，测量在两项正在进行的纵向研究（“强心脏研究”和“强心脏家庭研究”）中重复从美国原住民男性和女性身上收集的储存血液中的内源性激素。美洲原住民是心血管疾病和糖尿病发病率较高的少数群体。 我们的具体目标是： 1) 区分循环内源性雌激素、雄激素和性激素结合球蛋白 (SHBG) 的变化是否与男性和女性糖尿病患者随后的 CVD 事件相关； 2) 确定循环内源性雌激素、雄激素和性激素结合球蛋白（SHBG）水平是否与随后的糖尿病前期和糖尿病相关； 3）在男性和女性的成年寿命中，表征内源性雄激素和雌激素动态及其与颈动脉粥样硬化、心脏功能障碍和相关危险因素（特别是血糖失调和肥胖）的关系。 更好地了解性激素和心血管疾病之间的相互作用及其在衰老过程中的危险因素将广泛影响公共卫生策略、风险分层和心血管疾病的治疗。