Early menopausal hormone use influences brain regions used for visual working memory.

OBJECTIVE: The cognitive benefit of postmenopausal hormone use is controversial; however, timing of treatment close to menopause may increase the likelihood of preserving cognitive function. We examined the effects of early-initiation hormone use on visual working memory, hypothesizing that long-term hormone use is associated with greater brain activation during visual working memory. METHODS: This was a cross-sectional comparison of long-term early hormone users-current (n = 13) and past (n = 24; 2.1 +/- 1.0 years off hormones)-with never users (n = 18), using a visual memory task and functional magnetic resonance imaging (MRI). We evaluated 55 women older than 60 years at the University of Michigan's General Clinical Research Center. Hormone users had completed at least 10 continuous years of conjugated equine estrogens with or without medroxyprogesterone acetate, begun within 2 years of menopause. Women were excluded for illness, medication, intermittent estrogen use, phytoestrogen use, recent smoking, and MRI contraindications. The primary outcome was functional MRI-detected brain activity during the visual memory task. RESULTS: Compared with never users, both groups of hormone users had increased activation in the frontal and parietal cortices, insula, hippocampus, and cingulate; combined hormone users also had increased activation in the putamen and raphe (corrected P < 0.05 or uncorrected P < 0.001 with a priori hypothesis). Across the entire sample, the medial temporal cortex (P < 0.0001 right; P < 0.018 left) and right hippocampus (P < 0.0001) positively correlated with task performance. CONCLUSIONS: Hormone use was associated with increased brain activation during the visual memory task, in regions used for visual working memory. A positive correlation between activation and task performance suggests that early-initiation, long-term postmenopausal hormone use may benefit visual working memory.

Short-term hormone treatment modulates emotion response circuitry in postmenopausal women.

OBJECTIVE: To study the effects of combination hormone therapy (HT) on emotional processing in postmenopausal women with use of functional neuroimaging. DESIGN: A randomized, double-blind, placebo-controlled crossover study was performed. SETTING: A tertiary care university medical center. PARTICIPANT(S): Ten healthy postmenopausal women (mean age 56.9 years, SD = 1.4 years) were recruited. INTERVENTION(S): Women were assigned randomly to the order they received combined HT, 5 microg ethinyl E(2) and 1 mg norethindrone acetate, and placebo. Volunteers received HT or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. Subjects participated in a functional magnetic resonance imaging emotional processing task, where they were asked to rate emotional pictures as positive, negative, or neutral. MAIN OUTCOME MEASURE(S): Brain activation patterns were compared between HT and placebo conditions within subjects. RESULT(S): During negative emotional presentations, after subtracting the effect of neutral images, areas of significant differences between HT and placebo conditions were identified in the orbital, frontal, cingulate, and occipital cortices. During positive emotional image presentation there were significant differences between placebo and HT conditions within the medial frontal cortex. CONCLUSIONS: Short-term menopausal treatment with combination HT affects regional brain activity within areas implicated in emotional processing.

Enhanced neuroactivation during verbal memory processing in postmenopausal women receiving short-term hormone therapy.

OBJECTIVE: To study the effects of hormone therapy on brain activation patterns during verbal memory in postmenopausal women. DESIGN: A randomized, double-blind placebo-controlled cross-over study was performed. SETTING: A tertiary care university medical center. PATIENT(S): Ten healthy postmenopausal women (age range 56-60 years) were recruited from the local community. INTERVENTION(S): Women were randomized to the order they received combined hormone therapy, 5 microg of ethinyl E(2) and 1 mg of norethindrone acetate, and placebo. Volunteers received hormone therapy or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. A functional magnetic resonance imaging (fMRI) was performed at the end of each 4-week treatment using a verbal memory task. MAIN OUTCOME MEASURE(S): Brain activation patterns were compared between hormone therapy and placebo. RESULT(S): Hormone therapy was associated with increased activation in the left middle/superior frontal cortex (BA 6,9), medial frontal cortex and dorsal anterior cingulate (BA 24,32), posterior cingulate (BA 6), and left inferior parietal cortex (BA 40) during memory encoding. All regions were significant with correction for multiple comparisons. CONCLUSION(S): Hormone therapy increased neural activation in frontal and parietal areas in postmenopausal women during a verbal memory task.

Impact of combined estradiol and norethindrone therapy on visuospatial working memory assessed by functional magnetic resonance imaging.

CONTEXT: Hormones regulate neuronal function in brain regions critical to cognition; however, the cognitive effects of postmenopausal hormone therapy are controversial. OBJECTIVE: The goal was to evaluate the effect of postmenopausal hormone therapy on neural circuitry involved in spatial working memory. DESIGN: A randomized, double-blind, placebo-controlled crossover study was performed. SETTING: The study was performed in a tertiary care university medical center. PARTICIPANTS: Ten healthy postmenopausal women of average age 56.9 yr were recruited. INTERVENTIONS: Volunteers were randomized to the order they received hormone therapy (5 microg ethinyl estradiol and 1 mg norethindrone acetate). Subjects received hormone therapy or placebo for 4 wk, followed by a 1-month washout period with no medications, and then received the other treatment for 4 wk. At the end of each 4-wk treatment period, a functional magnetic resonance imaging study was performed using a nonverbal (spatial) working memory task, the Visual Delayed Matching to Sample task. MAIN OUTCOME MEASURE: The effects of hormone therapy on brain activation patterns were compared with placebo. RESULTS: Compared with the placebo condition, hormone therapy was associated with a more pronounced activation in the prefrontal cortex (BA 44 and 45), bilaterally (P < 0.001). CONCLUSIONS: Hormone therapy was associated with more effective activation of a brain region critical in primary visual working memory tasks. The data suggest a functional plasticity of memory systems in older women that can be altered by hormones.