Differential effects of estrogen and micronized progesterone or medroxyprogesterone acetate on cognition in postmenopausal women

Objective To investigate possible differential effects of the coadministration of conjugated equine estrogen (CEE) and a placebo (CEE + PL), CEE and medroxyprogesterone acetate (CEE + MPA), or CEE and micronized P (CEE + MP) on aspects of cognitive functioning in naturally postmenopausal women. Design Double-blind, randomized, controlled trial. Setting Gynecologic screening occurred at a university hospital, and neuropsychological testing took place in a university laboratory. Patient(s) Twenty-four naturally menopausal women with an intact uterus who had never used hormone therapy were recruited by means of newspaper advertisements. All completed the study. Intervention(s) A battery of mood and neuropsychological tests was administered. Women were randomly assigned to receive CEE + PL (n = 7), CEE + MPA (n = 9), or CEE + MP (n = 8). The tests were readministered 12 weeks later. Main Outcome Measure(s) Standardized tests of mood, verbal memory, working memory, spatial abilities, and visual–spatial sequencing, and assays of serum sex hormone levels. Result(s) Mood improved after treatment in all groups. No changes in scores occurred over time in any cognitive test in the group that received CEE + PL. Only the CEE + MP group had a significant decrease in their delayed verbal memory scores from baseline to after treatment. The CEE + MP-treated women performed significantly better on a test of working memory than women in the other two groups. Conclusion(s) Coadministration of CEE with MPA or MP caused differential effects on aspects of memory in postmenopausal women. These findings need to be replicated with a larger sample size before their potential clinical implications can be determined.