Estrogen replacement therapy and cognitive functions in healthy postmenopausal women: a randomized trial

Gorenstein, Clarice; Rennó, Joel; Filho, A. H. G. Vieira; Gianfaldoni, Arlete; Gonçalves, Marcelo; Halbe, Hans Wolfgang; Fernandes, César Eduardo; Demetrio, Frederico Navas

doi:10.1007/s00737-011-0230-6

Cited by 25 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the variable outcomes associated with combined hormone treatments, investigations of unopposed estradiol have largely found positive or neutral effects on verbal cognition, although results from studies using conjugated equine estrogens (CEE) have been less conclusive (Dumas et al, 2010; Espeland et al, 2013; Gleason et al, 2006; Gorenstein et al, 2011; Maki, 2012; Maki and Sundermann, 2009; Sherwin, 2012; Sherwin and Grigorova, 2011; Wroolie et al, 2011). We expected that short-term estradiol administration would positively impact verbal cognition.…”

Section: Discussionmentioning

confidence: 99%

Distinct cognitive effects of estrogen and progesterone in menopausal women

Berent-Spillson

Briceño

Pinsky

et al. 2015

Psychoneuroendocrinology

View full text Add to dashboard Cite

The effects of postmenopausal hormone treatment on cognitive outcomes are inconsistent in the literature. Emerging evidence suggests that cognitive effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestin. There are very few studies of unopposed progesterone in postmenopausal women, and none that use functional neuroimaging, a sensitive measure of neurobiological function. In this study of 29 recently postmenopausal women, we used functional MRI and neuropsychological measures to separately assess the effects of estrogen or progesterone treatment on visual and verbal cognitive function. Women were randomized to receive 90 days of either estradiol or progesterone counterbalanced with placebo. After each treatment arm, women were given a battery of verbal and visual cognitive function and working memory tests, and underwent functional MRI including verbal processing and visual working memory tasks. We found that both estradiol and progesterone were associated with changes in activation patterns during verbal processing. Compared to placebo, women receiving estradiol treatment had greater activation in the left prefrontal cortex, a region associated with verbal processing and encoding. Progesterone was associated with changes in regional brain activation patterns during a visual memory task, with greater activation in the left prefrontal cortex and right hippocampus compared to placebo. Both treatments were associated with a statistically nonsignificant increase in number of words remembered following the verbal task performed during the fMRI scanning session, while only progesterone was associated with improved neuropsychological measures of verbal working memory compared to placebo. These results point to potential cognitive benefits of both estrogen and progesterone.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct cognitive effects of estrogen and progesterone in menopausal women

Berent-Spillson

Briceño

Pinsky

et al. 2015

Psychoneuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Behavioral animal and human subject studies show that the effects of estrogen on cognition are task, time, and dose dependent. That estrogen has been shown to significantly improve performance on PFC dependent cognitive tasks such as the N‐back task [Keenan et al, ], Stroop task [Krug et al, ], and digit‐span forward task [Gorenstein et al, ] in human subjects and the delayed response task in rodents [Inagaki et al, ] and non‐human primates [Rapp et al, ], suggests estrogen may play a significant role in mediating executive domains such as working memory and sustained attention. The cognitive load required by a particular task also appears to play a role in both the extent to which ET enhances cognitive function and brain activation with more obvious effects of estrogen at higher cognitive loads [Dumas et al, ].…”

Section: Discussionmentioning

confidence: 99%

Estrogen and the prefrontal cortex: Towards a new understanding of estrogen's effects on executive functions in the menopause transition

Shanmugan

Epperson

2012

Human Brain Mapping

179

138

View full text Add to dashboard Cite

Midlife decline in cognition, specifically in areas of executive functioning, is a frequent concern for which menopausal women seek clinical intervention. The dependence of executive processes on prefrontal cortex function suggests estrogen effects on this brain region may be key in identifying the sources of this decline. Recent evidence from rodent, nonhuman primate, and human subject studies indicates the importance of considering interactions of estrogen with neurotransmitter systems, stress, genotype, and individual life events when determining the cognitive effects of menopause and estrogen therapy.

show abstract

“…In a separate study, Smith and colleagues reported that early initiation of HT in menopausal women is associated with increased hippocampal and posterior cingulate cholinergic activity (Smith et al, 2011). Similarly, Gorenstein et al evaluated the effect of estrogen replacement therapy on verbal cognitive performance of middleaged postmenopausal women and reported better performance of the estrogen group on digit span-forward and on the recall of the easy stimuli on the verbal-paired associates tests despite the magnitude of benefits is moderate (Gorenstein et al, 2011). …”

Section: Healthy Cell Bias Of Estrogen Action: Consolidation Of Cmentioning

confidence: 99%

Estrogen Regulation of Mitochondrial Bioenergetics

Yao

Brinton

2012

Advances in Pharmacology

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised aerobic glycolysis pathway coupled with oxidative stress is first accompanied by a shift toward a ketogenic pathway that eventually progresses into fatty acid oxidation (FAO) pathways and leads to white matter degeneration and overproduction and mitochondrial accumulation of β-amyloid. Estrogen-induced signaling pathways converge upon the mitochondria to enhance mitochondrial function and to sustain aerobic glycolysis coupled with citric acid cycle-driven oxidative phosphorylation to potentiate ATP (Adenosine triphosphate) generation. In addition to potentiated mitochondrial bioenergetics, estrogen also enhances neural survival and health through maintenance of calcium homeostasis, promotion of antioxidant defense against free radicals, efficient cholesterol trafficking, and beta amyloid clearance. Significantly, the convergence of E2 mechanisms of action onto mitochondria is also a potential point of vulnerability when activated in diseased neurons that exacerbates degeneration through increased load on dysregulated calcium homeostasis. The “healthy cell bias of estrogen action” hypothesis examines the role that regulating mitochondrial function and bioenergetics play in promoting neural health and the mechanistic crossroads that lead to divergent outcomes following estrogen exposure. As the continuum of neurological health progresses from healthy to unhealthy, so too do the benefits of estrogen or hormone therapy.

show abstract

Estrogen replacement therapy and cognitive functions in healthy postmenopausal women: a randomized trial

Cited by 25 publications

References 38 publications

Distinct cognitive effects of estrogen and progesterone in menopausal women

Distinct cognitive effects of estrogen and progesterone in menopausal women

Estrogen and the prefrontal cortex: Towards a new understanding of estrogen's effects on executive functions in the menopause transition

Estrogen Regulation of Mitochondrial Bioenergetics

Contact Info

Product

Resources

About