Effect of Estrogen & Stress for Postmenopausal Women
Condition: Aging
Study type: Interventional
Phase: Phase 2

Summary: 
      The study tests the hypothesis that estradiol administration exacerbates the effects of the
      stress hormone cortisol on cognition and mood for postmenopausal women. This randomized,
      placebo-controlled, double-blind study was designed to examine the effects of an eight-week
      trial of transdermal estradiol replacement therapy (0.10 mg/day) in combination with 4 days
      of oral hydrocortisone (90 mg/day in 3 daily doses of 30 mg per dose) in the last week of
      hormone therapy on cognition and mood in healthy postmenopausal women. Forty cognitively
      healthy postmenopausal women were randomized to receive either placebo or estradiol skin
      patches for 8 weeks. In the middle of the 7th week (day 57), subjects in each group were
      again randomized to receive either a placebo tablet or an oral hydrocortisone tablet 3x/day
      for 4 days. Memory testing and blood collection occurred at baseline, at week 4, and again at
      week 8.
    

Detailed description: 
      Estrogen replacement has been associated with improved learning and memory in both animal and
      human studies. However, there is some evidence to suggest that "stress" has a detrimental
      effect on learning for female animals who still have naturally circulating estrogen.
      Interestingly, when the effects of this hormone are blocked in the body, stress no longer
      impairs learning. Several investigators have raised the possibility that the physiological
      response to stress may be exaggerated for women compared to men. Gender differences in
      biological systems that control the release of gonadal and stress hormones may explain why
      estrogen is beneficial for women under nonstressed conditions, but detrimental for them under
      stressed conditions. To date, no study has carefully controlled or manipulated both estrogen
      use and cortisol levels to further explore this issue. In this placebo-controlled, double
      blind, parallel-group design clinical study we will evaluate whether estrogen use exacerbates
      stress-related impairments in cognition for healthy postmenopausal women. Forty subjects will
      receive either 0.10 mg/day of transdermal beta-estradiol or a placebo skin patch for 8 weeks.
      In the last week of treatment, subjects will receive 90 mg/day of oral hydrocortisone or a
      placebo for 4 consecutive days. Scores on tests of memory, attention, and mood, as well as
      blood levels of estrogen and cortisol will be assessed at baseline, and at weeks 4 and 8. We
      predict that the estrogen+cortisol combination will have a deleterious effect on cognition
      and mood relative to the effects of either hormone administered alone. The results of this
      study are likely to provide important information regarding not only the nature of the
      interaction between these hormonal systems that occurs in response to stress, but also the
      conditions under which the beneficial effects of estrogen may be overshadowed.
    

Intervention name(s): Climara; Hydrocortone
Intervention type(s): Drug; Drug
Intervention MeSH terms: Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: cognition; estradiol; cortisol; postmenopause