The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)
研究概览
简要总结
This study will focus on how estrogen affects parts of the brain associated with memory and how the effect of estrogen is altered with aging in postmenopausal women.
详细描述
The broad goal of this proposal is to determine the effect of aging on areas of the brain whose function is impacted by gonadal steroids in women. The overarching hypothesis is that aging differentially alters the effects of estrogen on the brain. Our preliminary data indicated that aging alters the effect of estrogen on brain regions involved in cognition and thus, the current study focused on the impact of aging on functional changes induced by estrogen in cortical and subcortical areas associated with verbal working memory and declarative/episodic memory.
As our model, we will use women in whom the absence of gonadal function makes it possible to control the duration and amount of estrogen exposure, specifically postmenopausal women who are younger (45-55) or older (65-80) who receive either oral or transdermal estradiol to achieve premenopausal early follicular phase estradiol levels.. We evaluate the effects of low dose estrogen exposure at 48 hr and 1 month to determine whether the short-term changes in brain regions involved in cognition with low dose estrogen exposure seen in our preliminary studies are confirmed and whether changes with short-term estrogen exposure persist with more prolonged exposure, a finding that would have enormous clinical relevance. These studies, using sophisticated neuroimaging tools (structural and functional magnetic resonance imaging [MRI] and [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography [FDG-PET]), provide a unique window into the brain in women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization was performed by the Research Pharmacy and the investigative team was blinded.
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •young postmenopausal (age 45-55) or older (age 65-80) postmenopausal women
- •otherwise healthy, non-obese women with normal blood pressure and a history of normal menopause, defined by the absence of menses for at least 12 months
- •prescription hormone replacement treatment discontinued at least 3 months before study
- •Normal or corrected normal vision
- •Intelligence quotient (IQ) > 70 on the Wechsler Adult Reading Test (WTAR)*
- •Absence of Mild Cognitive Impairment (MCI) and depression on the Mini Mental State Examination (MMSE)** and Beck Depression Inventory II (BDI-II).***
- •Normal mammogram or breast MRI within the past 2 years
- •Exclusion Criteria
- •On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment within three months of study
- •History of radiotherapy or chemotherapy.
- •Absolute contraindications to the use of physiologic replacement doses of estrogen and/or history of coronary artery disease
- •History of breast cancer, blood clot, pulmonary embolus, hypercoagulability and stroke.
- •On centrally acting medications
- •History of head trauma and/or neurologic disorder
- •Contraindication to MRI (eg. metal implants) or PET imaging (eg. PET imaging studies in the previous 12 months)
- •Concurrent participation in research studies involving medications and/or PET scans.
- •Left handedness.
- •Current breast lump(s) or family/genetic history of breast cancer in younger women (< 40 years old).
- •Current smoking
排除标准
- 未提供
研究组 & 干预措施
Young postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
干预措施: Estradiol oral capsule (Drug)
Young postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
干预措施: transderman estrogen patch (Drug)
Older postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
干预措施: Estradiol oral capsule (Drug)
Older postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
干预措施: transderman estrogen patch (Drug)
Young postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
干预措施: trasdermal placebo patch (Drug)
Young postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
干预措施: placebo oral capsule (Drug)
Older postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
干预措施: trasdermal placebo patch (Drug)
Older postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
干预措施: placebo oral capsule (Drug)
结局指标
主要结局
Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)
时间窗: baseline to 1 month
Change in extracted beta coefficients of the blood oxygen level dependent (BOLD) signal response to a cognitive task (N-back) in the DLPFC (x,y,z coordinates = -34 44 16) from baseline to 1 month as a function of aging and estrogen (young vs older and estrogen vs placebo). A positive change indicates an increase in oxygen utilization (inferring increased neuronal functioning) between baseline and treatment during the cognitive task, while a negative change indicates a decrease in oxygen utilization between baseline and treatment during the cognitive task.
次要结局
未报告次要终点
研究者
Janet E. Hall, MD
Associate Physician
Massachusetts General Hospital