Short-Term Use of Estradiol for Depression in Perimenopausal and Postmenopausal Women: A Preliminary Report

Cohen, Lee S.; Soares, Cláudio N.; Poitras, Jennifer R.; Prouty, Jennifer; Alexander, Allison B.; Shifren, Jan L.

doi:10.1176/appi.ajp.160.8.1519

Cited by 154 publications

(85 citation statements)

References 18 publications

(13 reference statements)

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“…S10), a large body of evidence (18) demonstrates that depression-like behavior in the TST and FST varies as a function of the estrous cycle. Furthermore, there are several studies that report that estrogen replacement therapy is beneficial to women who suffered postpartum and perimenopausal affective disorders (18,26,27). We show here that E2 reverses CMS-induced behavioral modifications in female mice.…”

Section: Discussionsupporting

confidence: 56%

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Luo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Mechanisms underlying the female preponderance in affective disorders are poorly understood. Here we show that hippocampal nitric oxide (NO) plays a role in the sex difference of depressionlike behaviors in rodents. Female mice had substantially lower NO production in the hippocampus and were significantly more likely to display negative affective behaviors than their male littermates. Eliminating the difference in the basal hippocampal NO level between male and female mice mended the sex gap of affective behaviors. Estradiol exerted a positive control on hippocampal NO production via estrogen receptor-β-mediated neuronal NO synthase expression. Thus, low estrogen in the female hippocampus accounts for lower local NO than in the male hippocampus. Although estrogen has important significance in modulating affective behaviors, it is not estrogen but NO in the hippocampus that mediates the sex difference of affective behaviors directly, because hippocampal NO was necessary for the behavioral effects of estradiol, and NO was an independent factor in modulating behaviors. Stress promoted hippocampal NO production in males because of glucocorticoid release, thus leading to local NO excess. In contrast, stress suppressed NO production in females because of decreased estrogen, thereby resulting in hippocampal NO shortage. Whereas activating cAMP response element binding protein (CREB) rescued the depression-like effects of the intrahippocampal NO donor diethylenetriamine/nitric oxide adduct (DETA/NONOate), inactivating CREB abolished the antidepressant-like effects of the intrahippocampal NO donor DETA/NONOate. Our findings suggest a molecular mechanism underlying the sex difference of affective behaviors.A ffective disorders such as depression and anxiety, lifethreatening and highly prevalent stress-related disorders, rank among the top causes of worldwide disease burden and disability (1, 2). It is commonly suggested that a female preponderance in depression and anxiety is universal and substantial. The prevalence of depression and anxiety for women is approximately twice that for men (2-6). Although there are advocates for the implications of hypothalamic-pituitary-adrenal axis hyperactivity in the sex differentiation in some expressions of both depression and anxiety (7), it is not clear what underlies the sex gap in these affective disorders.Neuronal nitric oxide synthase (nNOS) has been implicated in the psychiatric disorders characterized by depression (8, 9), schizophrenia (10), and aggressiveness (11). We recently demonstrated that hippocampal nNOS mediates the stress-related depressive behaviors of glucocorticoids (9) and the role of 5-hydroxytryptamine receptor 1A (5-HT1A) receptor in modulating anxiety-related behaviors (12). Evidence from clinical and biological studies indicates that the hippocampus plays an important role in major depression disorder (13). We found that chronic mild stress (CMS) increased hippocampal NO production by nNOS in male mice (6-9). In contrast, CMS diminished hippocampal NO prod...

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Section: Discussionsupporting

confidence: 56%

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Luo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…There are numerous studies that have demonstrated the beneficial effects of oestrogen on mood in midlife women (52)(53)(54)(55). The Revised Global Consensus Statement on Menopausal Hormone Therapy (56) states that "MHT (menopausal hormone therapy) may be beneficial in improving mood in early postmenopausal women with depressive and/or anxiety symptoms.…”

Section: Treatmentmentioning

confidence: 99%

Depression in midlife women

Sassarini

2016

Maturitas

116

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Depression is one of the leading causes of disease-related disability in women, and they are nearly twice as likely as men to suffer from an episode of depression. The difference begins in early life and persists through to mid-life, and as such, these reproductive years have been labelled by some as a 'window of vulnerability'. The prevalence has been reported to be particularly high during the menopausal transition, but there is no consensus supporting a direct association with reproductive status. This may be partly due to methodological limitations and inconsistencies in the available studies, resulting from a large number of confounding factors. In addition, relationships between sex hormones and the neurotransmitters purported to be responsible for depression are complex. What appears to be universally accepted is that treatment, with oestrogen, for low mood in women during midlife years may be beneficial, and should be considered. Key Words Depression MidlifeSexual dimorphism Receptor polymorphisms SearchingAll searches were conducted in PUBMED and EMBASE. The following search terms were combined using Boolean rules: depression, menopause, midlife, women. All searches were updated June 2016.Searching of grey literature or unpublished literature was not undertaken. Papers published in languages other than English were not reviewed.The titles and abstracts of records retrieved by the searches were sifted for relevance, with potentially significant publications obtained in full text.

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“…Demographics, Historical Variables, Symptom Ratings: At each clinic visit, we administered the following rating scales: 1) the Beck Depression Inventory (BDI) 17 (average scores and the number of women with scores of ≥ 16, a standard cut-off score indicating clinically significant symptoms, 2) the Center for Epidemiologic StudiesDepression Scale (CES-D) 18 (mean scores), and 3) VAS symptom inventory rating the severity (range: none to extreme) of 23 mood and behavioral symptoms (previously described. 14 ) including the following: inability to enjoy usual activities, excessive worrying, increased appetite or cravings, weight gain, lack of energy, frequent sleep disturbance, problems concentrating, irritability, avoidance of social activities, early morning wakening, preoccupation with physical health, anxiety, tearfulness, emotional numbness, experiencing unpleasant life events, mood instability, emotional detachment, lack of motivation, depressed mood, feelings of letting people down, feeling detached or unreal, mood fragility, and feelings of being unable to cope.…”

mentioning

confidence: 99%

A Cross-Sectional Evaluation of Perimenopausal Depression

Steinberg

Rubinow²,

Bartko³

et al. 2008

J. Clin. Psychiatry

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Objective-Overall, the clinical spectrum of depression during the perimenopause is not well characterized. This cross-sectional study examined the following: 1) clinical characteristics of women who presented to the NIMH midlife mood disorders clinic (between March 1990 and January 2004) with perimenopausal major and minor depressions; 2) the impact on these measures of either a prior episode of depression or the presence of hot flushes.Method-Historical variables, reproductive status, symptom ratings, and plasma hormone measures were examined in 116 women who met research criteria for perimenopause-related depression (a current episode of major or minor depression according to the Structured Clinical Interview for DSM-IV or Primary Care Evaluation of Mental Disorders supplemented with a past history form).Results-Clinical characteristics did not differ in those women with first onset (39%) versus recurrent depressions or in those with (57%) and without hot flushes. Depressive episodes clustered in the later stages of the menopause transition and the first year postmenopause. Seven (6%) women reported a past postpartum major depression, and 55% of women reported a history of premenstrual dysphoria (PMD).Conclusions-We found no evidence that either hot flushes or a previous episode of depression conveys a distinct clinical profile in these women. The clustering of onsets of depression suggests that the hormone events that characterize the late menopause transition may be relevant to the onset of this form of depression. Finally, although we observed a high rate of PMD, neither postpartum depression nor PMD are consistent accompaniments of perimenopausal depression.

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Short-Term Use of Estradiol for Depression in Perimenopausal and Postmenopausal Women: A Preliminary Report

Abstract: Some perimenopausal women with depression may benefit from short-term use of estrogen therapy, and its role for postmenopausal depressed women warrants further investigation. Antidepressant benefit associated with estrogen therapy may be independent of improvement in physical symptoms.

Cited by 154 publications

References 18 publications

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Hippocampal nitric oxide contributes to sex difference in affective behaviors

Depression in midlife women

A Cross-Sectional Evaluation of Perimenopausal Depression

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