Estrogen and Serotonin on Changing Brain Chemistry
Condition: Menopause
Study type: Interventional

Summary: 
      The aim of this study is to examine the effects of estrogen and serotonin on cognition,
      emotional processing, and brain activation. The investigators will study the effects of acute
      tryptophan (TRP) depletion on cognition and mood in healthy menopausal women before and after
      estrogen replacement treatment (ERT). Using functional magnetic resonance imaging (fMRI), the
      investigators will identify differences in brain activation during memory tasks with and
      without TRP depletion and before and after estrogen therapy in order to determine which brain
      regions and cognitive functions are affected by each manipulation.
    

Detailed description: 
      The overarching purpose of this study is to further our understanding of the individual and
      interactive effects of the hormone estrogen and the neurotransmitter serotonin on certain
      aspects of cognition and brain activation in menopausal women ages 48 to 60 years. Women will
      undergo cognitive testing and fMRI sessions both before and after 6 weeks of either estrogen
      or placebo administration. We will recruit women who are across the first 10 years since
      their last menstrual period so that the investigators can gather information regarding the
      potential impact of time since menopause on our outcomes of interest. We anticipate that
      findings from this study will help scientist and clinicians to refine their use of estrogen
      therapy in menopausal women. In addition, should the role of serotonin be of utmost
      importance for maintenance of healthy cognition, these data aid future drug development to
      preserve health cognition and/or to treat dementias in which serotonin is an important
      factor. This proposal is both novel and timely as results from this study are likely to
      provide information critical to the on-going discussion regarding the risks and benefits of
      ET use in menopausal women.
    

Intervention name(s): estrogen patch; Amino acids; Placebo Patch; Placebo pills
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 150 subjects will be enrolled in a double blind placebo controlled study where they will be randomized to receive either treatment with 17β-estradiol (Vivelle Dot® 0.10 - 0.15 mg/day) or a look-alike placebo patch for a total of approximately 8 weeks. There will be four fMRI test sequences: two test sequences one week apart prior to estrogen treatment (ET) or placebo treatment (PT), and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. During each test day, all subjects will have their blood drawn at specific time intervals and undergo a battery of cognitive testing.While on the ET or PT treatment, all subjects will be instructed to change the patch every 3.5 days.; 31.5 mg of amino acids or 31.5 mg of lactose will be administered to subjects on each of their 4 test days. On 2 of the test days subjects will receive the active pills (amino acids) and on the other 2 test days subjects will receive the placebo pills (lactose).; placebo; There are 4 test days in this study. Each test day will involve the ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion), while during the other test they will contain a total of 31.5 g of amino acids.
Other intervention name(s): Vivelle-Dot®; L-Isoleucine; L-Leucine; L-Lysine; L-Methionine; L-Phenylalanine; L-Threonine; L-Valine; Placebo; lactose
Intervention MeSH terms: Estrogens
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cognitive difficulties; memory impairment; mood changes; brain activation