NEUROBIOLOGICAL EFFECTS OF LONG-TERM ESTROGEN REPLACEMENT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。随着我国女性老龄化人口的不断增加，绝经后妇女的身心健康的维持和改善问题与我们的社会息息相关。衰老会导致大脑功能的退化和阿尔茨海默病（AD）等痴呆症的高发病率。AD是一种毁灭性的疾病，给国家带来了巨大的经济负担。由于没有治愈方法或有效的治疗方法，预防策略对这种疾病尤为重要。许多研究表明，雌激素的使用可以提高认知能力，并可能预防或延缓老年痴呆症的发作。然而，雌激素对认知功能的长期保护作用尚不明确。我们的研究目的是研究女性的衰老过程，并评估绝经后雌激素治疗对健康脑功能的影响。此外，由于长期绝经后激素治疗的健康益处和风险（即乳腺癌）存在争议，与AD风险和生活质量相关的信息将有助于为老年妇女的卫生保健提供适当的建议。将通过布告栏公告、报纸广告和妇女健康登记处（对参加临床研究感兴趣的妇女数据库）招募60名妇女。她们的年龄必须在60岁以上并且在绝经后不间断地接受激素治疗或者不进行替代治疗。受试者将被分为三组，20人从未使用过绝经后激素治疗，20人只使用雌激素至少十年，20人使用雌激素和黄体酮至少十年。所有研究参与者将获得大脑解剖的磁共振成像（MRI）和功能磁共振成像（fMRI）。此外，受试者将接受正电子发射断层扫描（PET）扫描，以研究与认知有关的胆碱能神经递质系统。将进行激素水平测试和认知测试。将对获得的数据进行检查，以找出与雌激素加黄体酮方案或完全不使用激素相比，使用雌激素是否对大脑功能有最大的积极影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With the steady increase in our aging female population, issues concerning the maintenance and improvement of the physical and mental health of postmenopausal women are extremely relevant to our society. Aging leads to the deterioration of brain function and a higher incidence of dementias such as Alzheimer's disease (AD). AD is a devastating illness and presents a tremendous economic burden to the country. Since no cures or highly effective therapies exist, preventive strategies are of particular importance in this disease. A number of studies have suggested that estrogen use can enhance cognitive performance and possibly prevent or delay the onset of debilitating dementias. The long-term protective effects of estrogen on cognitive functioning, however, are not clearly established. The goal of our research is to study the aging process in women and evaluate the effects of postmenopausal estrogen therapy on healthy brain function. Furthermore, as the health benefits and risks (i.e. breast cancer) of long-term postmenopausal hormone therapy are debated, information relevant to AD risk and quality of life will assist in appropriate recommendations for the health care of aging women. Sixty women will be recruited through bulletin board announcements, newspaper advertisements and the Women's Health Registry (a database of women interested in participating in clinical research studies). They will be selected so that they are 60 years old or older and have either received hormone therapy without interruption after menopause or no replacement. The subjects will be recruited into three groups, 20 will have never used postmenopausal hormone therapy, 20 will have used estrogen only for at least ten years, and 20 will have used estrogen and progestin for at least ten years. Magnetic Resonance Image (MRI) of anatomy and functional MRI (fMRI) of the brain will be obtained in all study participants. In addition, subjects will undergo a positron emission tomography (PET) scan for the study of a cholinergic neurotransmitter system involved in cognition. Hormone levels will be tested and cognitive tests will be performed. Acquired data will be examined to find out whether estrogen use will have the greatest positive effect on brain capabilities compared to estrogen plus progestin regimen or using no hormones at all.