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

Love, Tiffany M.; Smith, Yolanda R.; Persad, Carol; Tkaczyk, Alan H.; Zubieta, Jon Kar

doi:10.1016/j.fertnstert.2008.12.056

Cited by 18 publications

(18 citation statements)

References 59 publications

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“…Estradiol receptors are located in a number of brain areas, including regions important for the autonomic, hormonal, and cognitive-emotional response to psychosocial stress (Love et al, 2010). The relation of stress to depression onset (Frank et al, 1994; Kendler et al, 1999; Kendler et al, 2000) and the altered function of the stress system in major depression (Burke et al, 2005; Lupien et al, 2009) suggest that modulation of the psychosocial stress response may be a mechanism through which estradiol fluctuation may contribute to MDD and PTSD risk.…”

Section: Discussionmentioning

confidence: 99%

Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle

Albert

Pruessner

Newhouse

2015

Psychoneuroendocrinology

169

105

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Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle – related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women.

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Section: Discussionmentioning

confidence: 99%

Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle

Albert

Pruessner

Newhouse

2015

Psychoneuroendocrinology

169

105

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“…To examine brain activation during emotional processing, subjects viewed emotional pictures from the International Affective Picture System (IAPS)[28] and rated each picture while in the MRI scanner as positive (pleasant), neutral, or negative (unpleasant) using a button press[29]. Subjects viewed sixty-four pictures from each emotional category, chosen from this set of pictures based on their affective rating by a normative female sample.…”

Section: Methodsmentioning

confidence: 99%

Postmenopausal hormone use impact on emotion processing circuitry

Shafir

Love

Berent-Spillson

et al. 2012

Behavioural Brain Research

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Despite considerable evidence for potential effects of estrogen on emotional processing, several studies of postmenopausal women who began hormone therapy (HT) remote from menopause report no effects of HT on emotional measures. As early HT initiation may preserve brain mechanisms, we examined effects of HT on emotional processing in postmenopausal women who started HT early after menopause. We performed a cross-sectional comparison of 52 postmenopausal women 66±5 years old, including 15 users of conjugated equine estrogen, 20 users of conjugated equine estrogen plus medroxyprogesterone acetate, and 17 who never used hormones (NT). All hormone users started therapy within two years of menopause, and received at least 10 years of continuous therapy. Outcomes were fMRI-detected brain activity and behavioral measures during an emotional processing picture rating task. During processing of positive pictures, NT women had greater activation than estrogen treated women in medial prefrontal cortex extending to the anterior cingulate, and more activation than estrogen plus progestin treated women in the insula. During processing of negative pictures, estrogen treated women had higher activation than NT women in the entorhinal cortex. Current compared to past HT users showed greater activation in the hippocampus and higher emotion recognition accuracy of neutral stimuli. Estrogen plus progestin treated women had slower response time than NT women when rating all pictures. In conclusion, hormone use was associated with differences in brain functional responses during emotional processing. These fMRI effects were more prominent than those observed for behavioral measures and involved brain regions implicated in cognitive-emotional integration.

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“…Neuroimaging studies of emotion processing in menopausal women are essentially lacking, and findings are thus far inconclusive (Table 6 ). A randomized placebo-controlled cross-over study including ten postmenopausal women portrayed an increased activation, though in different regions, during negative emotional stimuli processing, in both the placebo and estrogen-progestagen treated groups, and higher activation of the left medial frontal cortex during positive stimuli processing in the placebo group (Love et al, 2010 ). Later, a larger cross-sectional study of long-term HRT users also showed puzzling activation in estrogen treated women and non-users, and in current vs. past HRT users (Shafir et al, 2012 ).…”

Section: State-of-the-artmentioning

confidence: 99%

“…Later, a larger cross-sectional study of long-term HRT users also showed puzzling activation in estrogen treated women and non-users, and in current vs. past HRT users (Shafir et al, 2012 ). While Love et al found no effect on performance of the task (Love et al, 2010 ), Shafir et al found a slower response time in HRT users, but higher accuracy in picture rating among current users compared to past users (Shafir et al, 2012 ). In addition, greater regional activity in the dorsal lateral prefrontal cortex during high conflict resolution was found in one study investigating emotion regulation in eleven peri- and postmenopausal women (Frey et al, 2010 ).…”

Section: State-of-the-artmentioning

confidence: 99%

“…Monoaminergic projections throughout the prefrontal and parietal cortices are likely mediating the effect of estrogen and progestagens on emotion and mood. Cortical and limbic structures are key regulators in emotion processing; principally the dorsolateral prefrontal cortex, playing a role in the suppression of emotion, was less activated during negative emotional stimuli in estrogen-progestagen treatment compared to placebo (Love et al, 2010 ), and the amygdala, a key region in emotional learning, had diminished emotion-induced activation after estrogen-only treatment in the presence of dampened serotonergic function (Epperson et al, 2012 ).…”

Section: State-of-the-artmentioning

confidence: 99%

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Functional and molecular neuroimaging of menopause and hormone replacement therapy

Comasco

Frøkjær

2014

Front. Neurosci.

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The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women's brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the left inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in several cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain.

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

Cited by 18 publications

References 59 publications

Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle

Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle

Postmenopausal hormone use impact on emotion processing circuitry

Functional and molecular neuroimaging of menopause and hormone replacement therapy

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