The role of estrogen in mood disorders in women

Major depression is twice as common in women as men and depressive episodes appear to be more common in women with bipolar disorder. There is accumulating evidence that, in at least some women, reproductive-related hormonal changes may play a role in increasing the risk of depressive symptoms premenstrually, postpartum and in the perimenopausal period. In this review, the evidence for the role of hormonal fluctuations, specifically estrogen, in triggering depressive symptoms in a subgroup of women is summarized. In addition, the potential role of estrogen in triggering depressive symptoms via its effects on the serotonergic system, brain-derived neurotrophic factor and Protein Kinase C is reviewed.     

The role of estrogen in mood disorders in women

Major depression is twice as common in women as men and depressive episodes appear to be more common in women with bipolar disorder. There is accumulating evidence that, in at least some women, reproductive-related hormonal changes may play a role in increasing the risk of depressive symptoms premenstrually, postpartum and in the perimenopausal period. In this review, the evidence for the role of hormonal fluctuations, specifically estrogen, in triggering depressive symptoms in a subgroup of women is summarized. In addition, the potential role of estrogen in triggering depressive symptoms via its effects on the serotonergic system, brain-derived neurotrophic factor and Protein Kinase C is reviewed.     

From menarche to menopause: exploring the underlying biology of depression in women experiencing hormonal changes

Epidemiologic data consistently report an elevated prevalence of major depressive disorder (MDD) in women. This increase begins during adolescence and continues through the menopausal transition. Population-based clinical studies report an increase in the incidence of MDD during perimenopause compared to either the premenopausal or postmenopausal period. Evidence suggests that fluctuations and decline of hormonal levels are correlated with this observed increase in risk for MDD. A strong predictor of depression in the perimenopausal period is a previous history of MDD. However, recent studies revealed an increased risk of new onset depression in perimenopausal women without a history of MDD. Additionally, recent reports have indicated that the presence of vasomotor symptoms may be associated with an increased the risk for MDD. The objective of this paper is to review evidence that would support our hypothesis that neurotransmitter systems are affected by changes in hormonal status over the course of a woman's life, leading to increase vulnerability to perimenopausal depression. Relevant data from nonclinical experiments will be discussed in the context of observed clinical evidence of the risk for MDD before, during, and after the menopausal transition. A testable hypothesis will be proposed to advance our understanding of hormonal effects on mood.     

The associations between menopausal syndrome and depression during pre-, peri-, and postmenopausal period among Taiwanese female aborigines

Aim:  The aim of the study was to evaluate the association between physiological menopausal symptoms and depression during the pre-, peri-, and postmenopausal period among female Taiwanese aborigines.
Methods:  A total of 672 Taiwanese aboriginal women, aged 40–60 years, were recruited in the interviewing study and classified as pre-, peri-, and postmenopausal according to menstrual bleeding patterns in the previous 12 months. Then, the postmenopausal symptoms, depression, self-perceived health, family support, and associated demographic variables were assessed by questionnaire based on the results of interviewing by research assistants.
Results:  The results revealed that perimenopausal statuses are associated with depression and women with a perimenopausal status had a higher prevalence of depression than those with a premenopausal status. A higher score on physiological postmenopausal symptoms was found to be significantly associated with depression. Furthermore, somatic symptoms were associated with depression for pre-, peri-, and postmenopausal statuses. Moreover, sexual dysfunction and vasomotor symptoms were associated with depression only in the premenopausal status and postmenopausal status, respectively.
Conclusion:  Depression should be routinely evaluated for female Taiwanese aborigines consulting with physicians for menopause symptoms, especially for somatic symptoms. Furthermore, attention should be provided to premenopausal women with sexual dysfunction and postmenopausal women with vasomotor symptoms for depression.     

Psychologic distress during the menopausal years in women attending a menopause clinic.

OBJECTIVE: This study measures psychologic distress in women attending a menopause clinic to determine if significant differences exist between peri-menopausal and menopausal women. METHOD: Consecutive women attending a university hospital menopause clinic were administered the Brief Symptom Inventory (BSI) and a study questionnaire to determine menopausal symptoms, menstrual cycle status, and use of hormone replacement therapy (HRT). The BSI results were compared between menopausal and perimenopausal women, and to a normative sample of middle-aged women who were nonpatients. RESULTS: Two hundred and fifty-nine menopause clinic women completed the questionnaire: 113 perimenopausal and 146 menopausal women. There was significantly greater psychologic distress on the BSI among perimenopausal as compared to menopausal women on the global severity index, and each of the anxiety, hostility, somatization, depression, paranoid, and psychoticism subscales. Perimenopausal women met BSI caseness severity criteria significantly more often than did menopausal women on the global severity index, and on the subscales for depression, anxiety, and psychoticism. On the BSI, menopausal women showed results similar to those of a normative sample of nonpatient middle-aged women. CONCLUSIONS: Perimenopausal women attending menopause clinics have significantly higher levels of psychologic distress meeting case severity criteria on the BSI. Further research is warranted to define the subgroups of perimenopausal women who are at increased risk, in the hopes of developing effective interventions.     

Bladder and sexual function among women with multiple sclerosis

OBJECTIVE: Genitourinary dysfunction is common in women with multiple sclerosis (MS), yet few studies have evaluated the association between bladder and sexual dysfunction in these women. The aim of this study was to determine factors, including demographic and bladder function, associated with sexual dysfunction in a sample of women with MS. METHODS: One hundred and thirty-three women with MS completed questionnaires related to overall heath status, bladder function and sexual function. Response frequencies and percentages were calculated for questionnaire responses. Multivariate logistic regression analyses were performed to determine predictors of sexual dysfunction. RESULTS: Sixty-one per cent of the sample indicated that they had a problem with bladder control. Forty-seven per cent of respondents indicated that their neurological problems interfered with their sex life. Over 70% of the sample reported that they enjoyed, felt aroused and experienced orgasm during sexual activity. Not having a sexual partner and the indication of bothersome neurological problems were the best predictors of sexual dysfunction. Interestingly, patients bothered by their urge incontinence had higher levels of orgasm compared to women not bothered by urge incontinence. CONCLUSIONS: Although over half of the women reported voiding symptoms, most still enjoyed, felt aroused and could experience orgasm. Neurological symptoms and lacking a sexual partner emerged as the best predictors of sexual dysfunction. Urge incontinence may not be a risk factor for an orgasm. Our findings elucidate the complex nature of sexual dysfunction in women with MS.     

Menopause-related quality of life in chronically mentally ill women

OBJECTIVE: Menopause is an important life event that has not yet been well characterized among women with severe mental illness. Our goal was to evaluate menopause-related quality of life among severely mentally ill women. METHOD: We conducted a cross-sectional assessment of perimenopausal and postmenopausal women, ages 45-55, diagnosed with schizophrenia/schizoaffective disorder, bipolar disorder, or major depression, who were receiving inpatient or outpatient psychiatric care. Women were compared regarding menopausal symptoms and quality of life using the Menopause Specific Quality of Life Scale (MENQOL). RESULTS: Women with severe mental illnesses who were peri- and post-menopausal experienced considerable vasomotor, physical, sexual, and psychosocial symptoms related to menopause. On seven of 29 MENQOL items, women with major depression reported problems significantly more often than women with other serious mental illnesses. CONCLUSIONS: This preliminary study indicates that psychiatrists and other physicians should consider the frequency and overlap of menopausal and psychiatric symptoms among women with serious mental illness in this age group.     

Effects of Menopause on Seizures in Women with Epilepsy

Summary: Purpose: Although important associations between epilepsy and women's hormonal phases are described, the relation of menopause to epilepsy has received little attention. Methods: By using a structured interview, we studied menopausal women with epilepsy seen at the University of Maryland Epilepsy Center over a 1-year period from 1994 to 1995. We analyzed the characteristics and temporal relation of the seizures to menopause and compared the frequency and severity of the seizures with those in a similar group of premenopausal women. Results: We identified 61 menopausal women (46 who were postmenopausal and 15 perimenopausal) and compared them with 46 premenopausal women. No statistically significant differences were noted in either the frequency or the severity of seizures comparing all menopausal or only postmenopausal with premenopausal women. However, 12 (20%) of the 61 menopausal women noted that their seizures first began during or after menopause, with eight having no proven cause for their seizures. Many individual women described changes in their seizures with menopause. Among the 61 menopausal women, 49 had established epilepsy before the onset of menopause, and 20 (41%) reported worsening of their seizures with menopause, 13 (27%) noted improvement, and 16 (33%) described no changes. These observations were similar for peri- and post-menopausal women. Of the 15 menopausal women taking hormone replacement therapy, the six taking progestin were significantly less likely to report worsening of their seizures. Conclusions: These findings support the view that hormonal influences are important in women with seizures. Although, in aggregate, menopausal (combined perimenopausal and post-menopausal) and postmenopausal women's seizures were similar in frequency and severity to those of other women, menopause was associated with changes in seizures for some women. Moreover, menopause may be a previously unrecognized factor for some new-onset seizures. The relations between menopause and epilepsy deserve to be more fully investigated.     

Depressive symptoms in the perimenopause: prevalence, assessment, and guidelines for treatment.

This review describes the biological changes occurring in perimenopause and analyzes epidemiological studies that shed light on the relationship between perimenopause and mood. The role of estrogen as a treatment for depressive symptoms is also examined. We found that a positive association may exist between depressive symptoms and the perimenopause, and that a prior history of depression may be associated with such symptoms. In most of the studies reviewed, the use of estrogen in replacement doses appears to improve depressive symptoms in perimenopausal patients who do not have major depression. We suggest an approach to the treatment of middle-aged women presenting with such symptoms. No careful study of the incidence of DSM-IV major depression associated with perimenopause has been done, and the efficacy of estrogen as a primary or adjunctive treatment for the disorder during perimenopause is unclear.     

Reproductive hormone sensitivity and risk for depression across the female life cycle: A continuum of vulnerability?

Throughout most of their lives, women are at greater risk for depression than men. Hormones and neurotransmitters share common pathways and receptor sites in areas of the brain linked to mood, particularly through the hypothalamic-pituitary-gonadal axis. It has been hypothesized that women presenting with episodes of depression associated with reproductive events (i.e., premenstrual, postpartum, menopausal transition) may be particularly prone to experiencing depression, in part because of a heightened sensitivity to intense hormonal fluctuations. The menopausal transition, for example, appears to represent a window during which some women might be more vulnerable to the development of first onset or recurrent depressive symptoms and major depressive episodes. In this review, we examine the association between hormone changes and increased risk of developing depression. Some of the underlying mechanisms that may contribute to such an increased risk are discussed critically, with a special emphasis on the events occurring during the menopausal transition. Last, we explore some of the clinical and therapeutic implications of hormone-modulated depression in women.     

Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report

OBJECTIVE: The authors examined the effect of a 4-week course of estrogen therapy on depression in perimenopausal and postmenopausal women. METHOD: Twenty-two depressed women who were either perimenopausal (N=10) or postmenopausal (N=12) received open-label treatment with transdermal 17beta-estradiol (100 micro g/day) for 4 weeks. The Montgomery-Asberg Depression Rating Scale and the Beck Depression Inventory were used to assess depressive symptoms, the Greene Climacteric Scale was used to assess menopause-related symptoms, and the Clinical Global Impression (CGI) was used to assess global clinical improvement in these women at baseline and after treatment. Remission of depression was defined as a score <10 on the Montgomery-Asberg Depression Rating Scale and a score 相似文献   

Venlafaxine in the treatment of depressive and vasomotor symptoms in women with perimenopausal depression

Perimenopause is often marked by vasomotor symptoms and dysphoria. Antidepressant studies have demonstrated decreased frequency and severity of hot flashes in breast cancer survivors and menopausal women. We hypothesized that venlafaxine would relieve both depressive and vasomotor symptoms in depressed perimenopausal women. Sixteen women fulfilling clinical criteria for climacteric phase and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for a depressive episode were enrolled in an open-label 8-week trial of extended-release venlafaxine. Depressive and climacteric symptoms were monitored using the Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A), Clinical Global Impression (CGI) scale, and Greene Climacteric Scale (GCS). Serum follicular stimulating hormone (FSH) and estradiol concentrations were monitored. Significant decreases in Ham-D and Ham-A scores and the GCS psychiatric subscale were seen after 2 weeks of treatment. In an intention-to-treat analysis, 81% of the subjects demonstrated a therapeutic antidepressant response (>50% decline in Ham-D score) and 75% achieved clinical remission (Ham-D score < or =7) after 8 weeks of venlafaxine therapy (75-225 mg/day). Total GCS scores declined 60%, and GCS vasomotor subscores decreased among those with vasomotor symptoms at baseline. These data suggest that venlafaxine treatment improves overall well-being, reduces depressive symptoms, and may diminish baseline vasomotor symptoms in depressed perimenopausal women. Further studies are warranted to investigate the utility of venlafaxine in perimenopausal depression.     

Consequences of impaired female sexual functioning: Individual differences and associations with sexual distress

A number of risk factors for sexual distress have been identified, including impairments in sexual function. However, for women, sexual function is only weakly associated with distress levels in many cases. One reason for this disconnect may be that impaired sexual function can have a variety of consequences for the individual's sexual experience and that some consequences may be more or less distressing to different people. Research suggests that some consequences of impaired sexual function may be more distressing to older women and/or for women in longer or less satisfying relationships. To examine the association between consequences of impaired female sexual function and distress, 75 women reporting one or more recurrent difficulties with sexual function in the past month were assessed. Frequency of sexual consequences including decreased physical pleasure, decreased sexual frequency, and negative partner emotional responses, were associated with sexual distress after controlling for the effects of sexual function. Additionally, a number of sexual consequences were rated as more distressing by older women and women in unsatisfying relationships. The idiosyncratic ways in which impairments in sexual function play out in the context of sexual activity may be an important target of future research and clinical interventions for sexual dysfunction.     

Migraine in perimenopausal women

Hormonal changes during the reproductive cycle are thought to account for the variation in migraine occurrence and intensity. Although the majority of women and the specialists treating them do not consider migraine as a component of the climacteric syndrome, many women, in fact, do experience migraine during perimenopause. If a woman already suffers from migraine, the attacks often worsen during menopausal transition. Initial onset of the condition during this period is relatively rare. Women with the premenstrual syndrome (PMS) prior to entering menopause are more likely to experience, during late menopausal transition, an increased prevalence of migraine attacks. Hormone replacement therapy (HRT) can be initiated during the late premenopausal phase and the first years of postmenopause to relieve climacteric symptoms. The effect of HRT on migraine, either as a secondary effect of the therapy or as a preventive measure against perimenopausal migraine, has been variously investigated. HRT preparations should be administered continuously, without intervals, to prevent sudden estrogen deprivation and the migraine attacks that will ensue. Wide varieties of formulations, both systemic and topical, are available. Treatment with transdermal patches and estradiol-based gels is preferable to oral formulations as they maintain constant blood hormone levels. Natural menopause is associated with a lower incidence of migraine as compared with surgical menopause; data on the role of hysterectomy alone or associated with ovariectomy in changing the occurrence of migraine are till now unclear.     

Increased frequency of depressive episodes during the menopausal transition in women with bipolar disorder: preliminary report

OBJECTIVE: Data are emerging in bipolar disorder regarding mood across phases of the female reproductive life, yet information about mood during the menopausal transition remains limited. The menopausal transition in women without mood disorders is associated with an increase in depression. This study assesses mood course during the menopausal transition in women with bipolar disorder. METHODS: We monitored mood episodes in 47 women with bipolar disorder ages 45-55 for 17.0+/-14.0 months with systematic treatment enhancement program for bipolar disorder (STEP-BD) standardized evaluations. Charts were additionally reviewed for menstrual status and menstrual history, as well as mood episode type, duration, frequency and history. RESULTS: During the menopausal transition 68% of women with bipolar disorder experienced at least one depressive episode. Depression (but not mood elevation) episode frequency significantly increased during the menopausal transition compared to reported frequency during patients' reproductive years. History of pre-menstrual and or post-partum mood instability did not predict perimenopausal mood episodes. CONCLUSIONS: Women with bipolar disorder experience a high frequency of depressive episodes during perimenopausal years and this frequency appears greater than during prior reproductive years. Prospective controlled studies are needed to better understand the course of mood episodes and to enhance the effectiveness of managing bipolar disorder during the menopausal transition.     

Menopause and cognitive impairment: A narrative review of current knowledge

A severe impairment of cognitive function characterizes dementia. Mild cognitive impairment represents a transition between normal cognition and dementia. The frequency of cognitive changes is higher in women than in men. Based on this fact, hormonal factors likely contribute to cognitive decline. In this sense, cognitive complaints are more common near menopause, a phase marked by a decrease in hormone levels, especially estrogen. Additionally, a tendency toward worsened cognitive performance has been reported in women during menopause. Vasomotor symptoms (hot flashes, sweating, and dizziness), vaginal dryness, irritability and forgetfulness are common and associated with a progressive decrease in ovarian function and a subsequent reduction in the serum estrogen concentration. Hormone therapy (HT), based on estrogen with or without progestogen, is the treatment of choice to relieve menopausal symptoms. The studies conducted to date have reported conflicting results regarding the effects of HT on cognition. This article reviews the main aspects of menopause and cognition, including the neuroprotective role of estrogen and the relationship between menopausal symptoms and cognitive function. We present and discuss the findings of the central observational and interventional studies on HT and cognition.     

Impact of sex and reproductive status on memory circuitry structure and function in early midlife using structural covariance analysis

Research on age‐related memory alterations traditionally targets individuals aged ≥65 years. However, recent studies emphasize the importance of early aging processes. We therefore aimed to characterize variation in brain gray matter structure in early midlife as a function of sex and menopausal status. Subjects included 94 women (33 premenopausal, 29 perimenopausal, and 32 postmenopausal) and 99 demographically comparable men from the New England Family Study. Subjects were scanned with a high‐resolution T1 sequence on a 3 T whole body scanner. Sex and reproductive‐dependent structural differences were evaluated using Box's M test and analysis of covariances (ANCOVAs) for gray matter volumes. Brain regions of interest included dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (iPAR), anterior cingulate cortex (ACC), hippocampus (HIPP), and parahippocampus. While we observed expected significant sex differences in volume of hippocampus with women of all groups having higher volumes than men relative to cerebrum size, we also found significant differences in the covariance matrices of perimenopausal women compared with postmenopausal women. Associations between ACC and HIPP/iPAR/DLPFC were higher in postmenopausal women and correlated with better memory performance. Findings in this study underscore the importance of sex and reproductive status in early midlife for understanding memory function with aging.     

Sexuality in women with epilepsy

Most women with epilepsy maintain normal reproductive cycles and sexual lives. However, a significant minority, approximately 20-30%, have some degree of sexual dysfunction, including problems with seizure exacerbation, libido, arousal, and orgasm. Fluctuating hormone levels may contribute to an array of reproductive cycling abnormalities. With regard to sexual dysfunction, there is some evidence of reduced genital blood flow in women with temporal lobe epilepsy. Other studies suggest that psychosocial factors, such as depression, feeling stigmatized, and being anxious about having seizures during sex, may contribute to the higher rates of sexual dysfunction in this patient population. Some antiepileptic drugs may adversely affect normal reproductive cycling and sexual function, particularly drugs that increase serotonergic transmission. Conversely, resective epilepsy surgery has been shown to restore sexual function. Treatments for sexual dysfunction include testosterone replacement, although transdermal testosterone replacement is not yet approved by the Food and Drug Administration for women. Given the possibility that women with epilepsy may experience inadequate vasocongestion during arousal, sildenafil may have a useful role, though it has not proved effective for women in general. This review focuses on potential sexual problems that are faced by women with epilepsy, with the suggestion that proper treatment may alleviate these problems.     

Orgasm-induced prolactin secretion: feedback control of sexual drive?

Recent studies from our laboratory have investigated the hormonal response to various forms of sexual stimulation, including film, masturbation, and coitus in both men and women. This series of studies clearly demonstrated that plasma prolactin (PRL) concentrations are substantially increased for over 1h following orgasm (masturbation and coitus conditions) in both men and women, but unchanged following sexual arousal without orgasm. Here we discuss evidence suggesting that the PRL response to orgasm may play an important role in the control of acute sexual arousal following orgasm. Supporting this position, chronic elevations of PRL (hyperprolactinemia) produce pronounced reductions in animal sexual activity, and significant reduction of libido and gonadal function in both men and women. These data suggest that PRL may represent a peripheral regulatory factor for reproductive function, and/or a feedback mechanism that signals CNS centres controlling sexual arousal and behaviour. Thus, we propose a theoretical model of the role of PRL as a neuroendocrine reproductive reflex.     

Premenstrual symptoms and perimenopausal depression

OBJECTIVE: The role of ovarian steroids in both premenstrual dysphoria and perimenopausal depression has led to the suggestion that these conditions represent expressions of the same underlying disorder. Premenstrual mood symptoms were evaluated in women with perimenopause-related depression. METHOD: Self-reports and daily symptom ratings during one menstrual cycle were examined in 70 depressed perimenopausal women attending a menopause clinic and 35 nondepressed perimenopausal women. RESULTS: Twenty-six percent of the depressed and 9% of the nondepressed women reported premenstrual symptoms. Thirty-one percent of the depressed and 20% of the nondepressed women met criteria for significant menses-related symptom cyclicity (at least a 30% increase in the average ratings of at least two of four measured negative mood symptoms in the premenstrual versus the postmenstrual week); 5 of these depressed women and none of the comparison subjects described premenstrual symptoms on self-reports. Finally, 21% of the depressed and 3% of the nondepressed women met criteria for premenstrual dysphoria (symptom cyclicity and at least moderate severity, with symptoms exceeding a minimum luteal symptom severity threshold of 2.5). CONCLUSIONS: A higher-than-expected rate of menses-related symptom cyclicity and premenstrual dysphoria was observed in perimenopausal depressed women. However, neither menses-related symptom cyclicity nor premenstrual dysphoria was an invariant accompaniment of perimenopausal depression. Additionally, the rate of premenstrual dysphoria was not predicted by initial self-reports.