Hormones and cognitive processing in early postmenopausal women

绝经后早期女性的激素和认知处理

• 批准号: 7782710
• 负责人: YOLANDA R SMITH
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7782710
• 关键词: Area; Arts; Brain; Brain region; Cerebrovascular Circulation; Cognition; Cognitive; Community Health; Crossover Design; Data; Double-Blind Method; Episodic memory; Estradiol; Estrogens; Functional Magnetic Resonance Imaging; Gonadal Steroid Hormones; Health; Hippocampus (Brain); Hormones; Hot flushes; Image; Intervention; Life; Magnetic Resonance Imaging; Measures; Memory; Menopausal Symptom; Menopause; Menstruation; Monitor; Moods; Neurobiology; Neurons; Neuropsychological Tests; Neurosecretory Systems; Neurotransmitters; Nurses' Health Study; Ovarian hormone; Pattern; Performance; Placebo Control; Placebos; Polysomnography; Post-Menopausal Hormone Replacement Therapy; Postmenopause; Preparation; Process; Progesterone; Progestin Therapy; Randomized; Randomized Clinical Trials; Recruitment Activity; Sleep; Staging; System; Task Performances; Techniques; Testing; United States; Vagina; Vaginal Gel; Variant; Vasomotor; Woman; Women' s Group; Women' s Health; age group; cognitive change; glucose metabolism; hormone therapy; improved; neural circuit; neuroimaging; neuropsychological; public health relevance; reproductive axis; response; treatment duration; volunteer

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.

描述（由申请人提供）：更年期是一个重要的生命阶段，对女性的认知健康具有影响。众所周知，卵巢激素可以调节神经内分泌生殖轴之外的神经元功能，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具体认知影响很难定义，并且可能会受到激素治疗 (HT) 开始时大脑健康状况以及情绪、睡眠和血管舒缩变化的影响。该合作应用结合了广泛的神经心理学评估和经过验证的最先进的神经影像技术，以试点测试有关 HT 对健康早期绝经后女性的神经生物学影响的机制假设。为了检验有关性腺类固醇对绝经期认知变化影响机制的假设，我们将招募 45-55 岁年龄组的早期绝经后女性，自上次月经以来的 12 至 24 个月内。采用随机双安慰剂对照交叉设计，36 名女性将被随机分配到治疗组（18 名仅使用雌二醇，18 名仅使用黄体酮）以及接受 3 个月激素和安慰剂的顺序。除了潮热和睡眠监测以及更年期症状评估之外，还将在每个治疗期结束时评估大脑功能测量。功能测量将包括志愿者在综合神经心理学测试中的表现，以及通过功能磁共振成像确定的大脑对情景言语和非言语记忆挑战的功能反应。具体目标包括： 1. 检查单独使用雌二醇对绝经后早期女性大脑功能的影响（通过言语和非言语认知任务期间的 fMRI-BOLD 激活来体现）；2. 确定单独使用黄体酮对大脑的影响绝经后早期女性的功能，通过言语和非言语认知任务期间的 fMRI-BOLD 激活来体现。公共健康相关性：这些研究将确定雌激素和黄体酮对绝经后早期女性认知过程的不同贡献。更好地了解性激素对大脑处理变化的具体贡献，将有助于准备 R01，以全面研究更年期早期激素使用的神经生物学，并最终使卫生界能够规划最有效维护认知健康的干预措施对女性来说。

项目成果

Distinct cognitive effects of estrogen and progesterone in menopausal women.

• DOI: 10.1016/j.psyneuen.2015.04.020
• 发表时间: 2015-09
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Berent-Spillson, Alison;Briceno, Emily;Pinsky, Alana;Simmen, Angela;Persad, Carol C.;Zubieta, Jon-Kar;Smith, Yolanda R.
• 通讯作者: Smith, Yolanda R.