Hormone therapy at early post-menopause increases cognitive control-related prefrontal activity

Romuald Girard,Julie Thomas,Michel Pugeat,Elise Météreau,Chen Qu,Jean-Claude Dreher

doi:10.1038/srep44917

Abstract

Clinical data have been equivocal and controversial as to the benefits to the brain and cognition of hormone therapy (HT) in postmenopausal women. Recent reevaluation of the role of estrogens proposed that HT may effectively prevent the deleterious effects of aging on cognition, and reduces the risks of dementia, including Alzheimer’s disease, if initiated early at the beginning of menopause. Yet, little is known about the effects of HT on brain activation related to cognitive control, the ability to make flexible decisions in relation to internal goals. Here, we used fMRI to directly test for a modulation of sequential 17β estradiol (2 mg/day) plus oral progesterone (100 mg/day) on task switching-related brain activity in women at early postmenopause. The results showed that HT enhanced dorsolateral prefrontal cortex recruitment during task switching. Between-subjects correlation analyses revealed that women who engaged more the dorsolateral prefrontal cortex showed higher task switching performance after HT administration. These results suggest that HT, when taken early at the beginning of postmenopause, may have beneficial effect on cognitive control prefrontal mechanisms. Together, these findings demonstrate that HT can prevent the appearance of reduced prefrontal cortex activity, a neurophysiological measure observed both in healthy aging and early dementia.

Highlights

In women in their 50 s is very minimal, it has been a challenge to detect a behavioral index of estrogen benefits in early postmenopausal women[2]
The absence of treatment effect on reaction time or error rate is in line with findings from the large KEEPS trial[19], which reported no cognitive benefit of estrogens in early postmenopausal women
The key question addressed by the current study was to investigate the modulatory effect of HT on early post-menopausal women’s brain activity while engaged in a cognitive control paradigm

Summary

Introduction

In women in their 50 s is very minimal, it has been a challenge to detect a behavioral index of estrogen benefits in early postmenopausal women[2]. Switching between cognitive operations is known to engage a bilateral prefronto-parietal network in healthy young individuals[14,15,16,17] and older subjects have disruptively low activity in this network, in prefrontal areas[18]. Based on these findings, we hypothesized that HT, as compared to placebo, will induce a relative increase in dorsolateral prefrontal activity during task switching in women at early post-menopause. We tested whether this potential increased prefrontal cortex activity with HT plays a beneficial effect on task switching performance

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Results

Conclusion