Hormones and cognitive processing in early postmenopausal women

描述（由申请人提供）：更年期是一个重要的生命阶段，对女性的认知健康有影响。已知卵巢激素调节神经内分泌生殖轴以外的神经元功能，影响对认知至关重要的大脑区域。然而，性腺类固醇对女性的特定认知影响一直难以定义，并且可能受到激素治疗（HT）开始时大脑健康以及情绪，睡眠和血管变化的混淆。这项合作应用结合了广泛的神经心理学评估和经验证的最先进的神经影像学技术，对有关HT在健康早期绝经后妇女中的神经生物学效应的机制假设进行了试验性测试。为了验证性腺类固醇激素对绝经期认知变化影响机制的假设，我们将招募年龄在45-55岁的绝经后早期女性，自末次月经后12 - 24个月内。采用随机双安慰剂对照交叉设计，36名妇女将被随机分配到治疗组（18名仅雌二醇，18名仅孕酮）和接受3个月激素和安慰剂的顺序。除了潮热和睡眠监测以及绝经期症状评估外，还将在每个治疗期结束时评价脑功能指标。功能测量将包括志愿者在综合神经心理学测试电池上的表现，以及用fMRI确定的对情景语言和非语言记忆挑战的大脑功能反应。具体目标包括：1.通过在语言和非语言认知任务期间的fMRI-BOLD激活来检查雌二醇单独对早期绝经后女性的脑功能的影响，以及2.通过在语言和非语言认知任务中的fMRI-BOLD激活，确定单独使用孕酮对绝经早期妇女脑功能的影响。公共卫生相关性：这些研究将确定雌激素和孕激素对早期绝经后妇女认知过程的不同贡献。更好地了解性腺性激素对大脑处理变化的具体贡献，将有助于准备R 01，以全面研究绝经早期激素使用的神经生物学，并最终使卫生界能够计划最有效地保护女性认知健康的干预措施。

DESCRIPTION (provided by applicant): Menopause is an important life stage with implications for cognitive health of women. Ovarian hormones are known to regulate neuronal function beyond the neuroendocrine reproductive axis, influencing brain regions critical to cognition. However, the specific cognitive effects of gonadal steroids in woman have been difficult to define and are potentially confounded by brain health at initiation of hormone therapy (HT), as well as mood, sleep and vasomotor changes. This collaborative application combines extensive neuropsychological assessment and validated state-of-the-art neuroimaging techniques, to pilot test mechanistic hypotheses concerning the neurobiological effects of HT in healthy early postmenopausal women. To test hypotheses concerning mechanisms of gonadal steroid effects on menopausal cognitive changes, we will recruit early postmenopausal women in the age group of 45-55 years, within 12 to 24 months since their last menstrual period. Using a randomized double placebo-controlled cross-over design, 36 women will be randomized to both the treatment group (18 estradiol only, 18 progesterone only) and the order they receive 3 months of hormones and placebo. Brain functional measures will be evaluated at the end of each treatment period, in addition to hot flash and sleep monitoring and menopausal symptom assessments. The functional measures will include the performance of the volunteers on a comprehensive neuropsychological testing battery, and the brain functional responses to episodic verbal and non-verbal memory challenges, as determined with fMRI. The Specific Aims include: 1. To examine the effect of estradiol alone on brain functioning in early post- menopausal women as manifested by fMRI-BOLD activation during verbal and non-verbal cognitive tasks and 2. To determine the effects of progesterone alone on brain functioning in early postmenopausal women as manifested by fMRI-BOLD activation during verbal and non-verbal cognitive tasks. PUBLIC HEALTH RELEVANCE: These studies will determine the differential contributions of estrogen and progesterone to cognitive processing in early postmenopausal women. A better understanding of the specific contributions of gonadal sex hormones to brain processing changes will allow for preparation of an R01 to comprehensively study the neurobiology of hormone use in early menopause and will ultimately allow the health community to plan interventions which may most effectively preserve cognitive health for women.