Early Menopause Hormone Treatment and Cognition
Condition: Menopausal Syndrome
Study type: Interventional

Summary: 
      The objective of this study is to evaluate the neurobiological effects of hormone therapy
      (HT) in healthy early postmenopausal women. The studies proposed in this project seek to
      define the association between different hormone forms (estradiol only and progesterone only)
      versus placebo on brain functional measures. The functional measures will include the
      performance of the volunteers on a comprehensive neuropsychological testing battery, and the
      brain functional responses to episodic memory (verbal and non-verbal) challenges as well as
      emotional processing determined with functional magnetic resonance imaging (fMRI).
    

Detailed description: 
      Specific Aims

      Aim 1. To examine the effects of estradiol alone on brain functioning in early
      post-menopausal women during verbal and non-verbal cognitive tasks.

      Hypothesis: It is expected that with estradiol treatment brain activation will be more
      prominent in the hippocampus and prefrontal cortical areas compared to placebo. The magnitude
      of activation in these regions will be positively correlated with task performance in the
      scanner and with the results of neuropsychological tests assessing verbal and non-verbal
      delayed recall.

      Aim 2. To determine the effects of progesterone alone on brain functioning in early
      postmenopausal women during verbal and non-verbal cognitive tasks.

      Hypothesis: It is expected that with progesterone treatment brain activation in the
      hippocampus and prefrontal cortical areas will be decreased compared to both the placebo
      condition (within subjects) and the estradiol condition (between subjects). Interindividual
      variations in the magnitude of activation in these regions will be positively correlated with
      task performance in the scanner and with the results of neuropsychological tests assessing
      verbal and non-verbal delayed recall.

      Aim 3. To determine the individual effects of estradiol and progesterone on brain functioning
      in early postmenopausal women during emotional processing stimuli.

      Hypothesis: During negative stimuli estradiol-treated women compared to placebo group, are
      expected to have increased activity in the amygdala, posterior cingulate, and orbitofrontal
      cortex, while in progesterone-treated women compared to placebo, decreased activity is
      expected in these brain regions.
    

Intervention name(s): Estradiol (E2); Progesterone (P10) x90; Progesterone (P10) x10
Intervention type(s): Drug; Drug; Drug
Intervention description(s): One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days; followed by one Progesterone (200mg) once a day, at the same time each day, for 10 days to slough endometrial lining; followed by one Placebo capsule once a day, at the same time each day, for 90 days.; One Progesterone capsule (200mg) once a day, at the same time each day, for 90 days; followed by one Placebo capsule (to mirror Progesterone capsule to slough endometrial lining in Estradiol recipients) once a day, at the same time each day, for 10 days ; followed by one Placebo capsule once a day, at the same time each day, for 90 days.; One Progesterone (200mg) capsule once a day for 10 days, to slough endometrial lining for patients taking Estradiol. Patients taking Progesterone will take an equivalent Placebo capsule during this time period.
Other intervention name(s): E2; P10; P10
Intervention MeSH terms: Estradiol; Progesterone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Women; Healthy; Menopausal; Hormone treatment