Enhanced Neuroactivation during Working Memory Task in Postmenopausal Women Receiving Hormone Therapy: A Coordinate-Based Meta-Analysis

Abstract

Background and aim: Hormone therapy (HT) has long been thought beneficial for controlling menopausal symptoms and human cognition. Studies have suggested that HT has a positive association with working memory, but no consistent relationship between HT and neural activity has been shown in any cognitive domain. The purpose of this meta-analysis was to assess the convergence of findings from published randomized control trials studies that examined brain activation changes in postmenopausal women.

Methods: A systematic search for fMRI studies of neural responses during working memory tasks in postmenopausal women was performed. Studies were excluded if they were not treatment studies and did not contain placebo or blank controls. For the purpose of the meta-analysis, 8 studies were identified, with 103 postmenopausal women taking HT and 109 controls.

Results: Compared with controls, postmenopausal women who took HT increased activation in the left frontal lobe, including superior frontal gyrus (BA 8), right middle frontal gyrus (BA 9), anterior lobe, paracentral lobule (BA 7), limbic lobe, and anterior cingulate (BA 32). Additionally, decreased activation is noted in the right limbic lobe, including parahippocampal gyrus (BA 28), left parietal lobe, and superior parietal lobule (BA 7). All regions were significant at p ≤ 0.05 with correction for multiple comparisons.

Conclusion: Hormone treatment is associated with BOLD signal activation in key anatomical areas during fMRI working memory tasks in healthy hormone-treated postmenopausal women. A positive correlation between activation and task performance suggests that hormone use may benefit working memory.

Keywords: ALE meta-analysis; functional magnetic resonance imaging; hormone therapy; neural activation; postmenopause; working memory.

Figure 1

Diagram of studies included in the present meta-analysis.

Figure 2

ALE map of the postmenopausal women during working memory. Decreased (green) and increased (red) activity following HT compared with the controls (p < 0.01; FDR-corrected; k > 100).

Figure 3

An ALE map presenting the increased activity in postmenopausal women undergoing HT during working memory tasks compared with the controls (p < 0.01; FDR-corrected; k > 100).

Figure 4

An ALE map presenting the decreased activity in postmenopausal women undergoing HT during working memory tasks compared with the controls (p < 0.01; FDR-corrected; k > 100).