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确定，并且可能与激素治疗（HT）开始时的大脑健康状况以及情绪、睡眠和血管舒缩变化相混淆。这项合作应用结合了广泛的神经心理学评估和最先进的神经成像技术，以试点测试关于激素对健康早期绝经后妇女的神经生物学影响的机制假设。为了验证性腺激素对绝经期认知变化的作用机制的假设，我们将招募年龄在45-55岁的早期绝经后妇女，在她们最后一次月经后的12 - 24个月内。采用随机双安慰剂对照交叉设计，36名妇女将被随机分为治疗组（18名仅使用雌二醇，18名仅使用黄体酮），并按顺序接受3个月的激素和安慰剂治疗。在每个治疗期结束时，除了潮热和睡眠监测以及更年期症状评估外，还将评估脑功能测量。功能测量将包括志愿者在综合神经心理测试中的表现，以及大脑对情景性语言和非语言记忆挑战的功能反应，这些都是用功能磁共振成像确定的。具体目标包括：1。通过fMRI-BOLD在言语和非言语认知任务中的激活来研究雌二醇单独对早期绝经后妇女脑功能的影响。通过fMRI-BOLD在言语和非言语认知任务中的激活来确定孕酮对早期绝经后妇女脑功能的影响。公共卫生相关性：这些研究将确定雌激素和黄体酮对早期绝经后妇女认知加工的不同贡献。更好地了解性腺性激素对大脑处理变化的具体贡献，将使R01的准备工作能够全面研究激素在更年期早期使用的神经生物学，并最终使卫生界能够计划干预措施，最有效地保护妇女的认知健康。

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.