Die Psyche in der Peri- und Postmenopause

During the menopausal transition biological and psychosocial factors are closely interrelated. The retrospective view on the previous life span and the attitudes towards the menopause influence the severity of climacteric complaints and symptoms as well as the acceptance of hormone therapy. Most women use hormones to suppress symptoms and not to prevent e. g. osteroporosis. Depressive symptoms become more frequent, however, more than half of the variance results from psychosocial factors and a positive history of depression. Sleep disturbances increase and can only in part be explained as the result of vasomotor symptoms or as correlates of depression. Sexual activity often changes. However, subjective feelings of being attractive and/or the quality of partnership are more important than the widely discussed genital atrophy and dyspareunia. Hormone therapy should be restricted to cases with objective vaginal atrophy. Sleep disturbances frequently respond to hormones, as well as minor depressive symptoms. More pronounced depressive syndromes should be referred to “classical” psychological and psychopharmacological treatments. Results obtained in studies with surgical menopause must not be easily generalized to women with a natural menopause.     

Sex differences in psychopathology: Of gonads, adrenals and mental illness

Stress-related disorders such as anxiety and depression are disproportionately prevalent in women. Women are more likely to experience depression and anxiety disorders during periods of marked hormonal fluctuations, suggesting that gonadal hormones are involved in stress pathology. Depression and anxiety are both associated with aberrant secretion of glucocorticoids, which also show marked fluctuations across the reproductive cycle and in response to gonadal steroids. Thus, interactions between gonadal and stress hormones may play a major role in predisposing females to stress-related disease. The purpose of this brief review is to highlight preclinical data regarding the role of estrogens in depression and anxiety-like behaviors. While it is evident the exogenous estrogens modulate affective behavior in rodents, there is some disagreement in the literature, perhaps related to experimental designs that vary with respect to administration parameters and stress. Beneficial effects of estrogens on mood are most likely due to estrogen receptor (ER)β signaling. The antidepressant and anxiolytic effects of ERβ are consistent with its role in attenuating glucocorticoid responses to stress, suggesting that estrogens, acting at ERβ, may improve mood by suppressing glucocorticoid hyperactivity. However, additional studies demonstrate that ERβ signaling in the hippocampus is sufficient to induce antidepressant and anxiolytic behaviors. Thus, ERβ may improve mood via primary actions on hypothalamic (i.e., paraventricular nucleus) and/or extra-hypothalamic sites. Overall, the preclinical research suggests that selective ER modulators targeting ERβ may be an attractive alternative or adjunct treatment to currently prescribed antidepressants or anxiolytics.     

To what extent do oral contraceptives influence mood and affect?

Background: Studies examining the effects of oral contraceptives (OCs) on mood, affect, and affect variability are reviewed. Methods: MEDLINE and PsycLIT data bases were examined to identify studies that compared OC users with nonusers using daily ratings of mood, affect, or affect variability. Results: Compared to non-users, OC users experience less variability in affect across the entire menstrual cycle, and less negative affect during menstruation (i.e. withdrawal bleeding). In women with OC-related negative mood and affect change, potential mediators of the relation between OCs and mood or affect were identified: a history of depression, psychiatric symptoms, dysmenorrhea, and premenstrual mood symptoms prior to OC use; a history of pregnancy-related mood symptoms; a family history of OC-related mood complaints; being in the postpartum period; and age. Furthermore, a lower ratio of progesterone to estrogen is associated with more negative mood change in women with a history of premenstrual emotional symptoms, higher progesterone to estrogen ratios are associated with increased negative mood effects in women without such a history, and monophasic OCs have a greater stabilizing effect on mood than triphasic OCs. Limitations: The ‘survivor effect’, psychological factors, and indirect pharmacological effects (e.g. weight gain) have not yet been systematically investigated. Furthermore, most studies have examined only negative mood or affect, as opposed to both positive and negative affect and affect variability; and few affect studies have assessed potential mediators of OC-related affect change. Conclusions: While the only consistent OC-related mood effects experienced by most women are beneficial, a subgroup of women do experience negative mood change. Future research must focus on expounding the individual difference and OC-related risk factors for negative mood change.     

Risk factors associated with the development of postpartum mood disorders

BACKGROUND: Various factors have been reported to be associated with the development of postpartum mood disorders. The relationship between postpartum mood disorders and putatively hormone-related phenomena such as premenstrual dysphoric disorder (PMDD) is unclear. This study attempts to determine whether such mood phenomena are risk factors for postpartum mood disorders. METHODS: Postpartum women (n=1800) were assessed for risk factors for postpartum mood disorders during the first 2-4 days after parturition. Of these, 133 were defined as "high risk" and 109 as "low risk" according to fixed criteria. A structured phone diagnostic interview was performed at 6-8 weeks postpartum to assess for the presence of postpartum depression or the blues. RESULTS: Premenstrual dysphoric disorder (PMDD), mood symptoms during the first 2-4 days postpartum, a past history of depression and mood symptoms during past oral contraceptive use, were found to be significant risk factors for postpartum mood disorders. Women at high risk for postpartum mood disorders had a 9.3-, 1.5-, 1.6- and 2.6-fold increase in risk for major depression, minor depression, the blues and adjustment disorder respectively compared to women at low risk. LIMITATIONS: While the study design is prospective, it is limited by the retrospective assessment of risk factors. CONCLUSIONS: This study provides preliminary evidence that putatively hormone-related phenomena such as PMDD are related to the occurrence of postpartum mood disorders. The results go some way to support the hypothesis that the etiology for postpartum mood disorders may be related to differential hormonal sensitivity. Such risk factors should be included in any assessment of the risk for these disorders.     

Depressive disorders and the menopause transition

Aim

Depressive disorders and symptoms are common among middle-aged women. The effects of hormones on depression remain unclear. This review aims to clarify the nature of depressive disorders during the menopause transition as well as their links with climacteric syndrome, sexuality, cardiovascular risk and cognitive function.

Material and methods

The recent literature on depressive disorders and menopause is reviewed.

Results and conclusions

Women are more vulnerable than men to depressive disorders. Endocrine influences have been postulated but differences in, for example, coping style and response to stress may also contribute to the gender difference in the prevalence of depressive disorders. Gender differences in socialization may lead to higher rates of depression in women. There are data top suggest that menopause and depression are associated, although there is not a common clear causative factor. Women with climacteric symptoms (hot flushes, night sweats, vaginal dryness and dyspareunia) are more likely to report anxiety and/or depressive symptoms. Bothersome vasomotor symptoms could be associated with sleep disturbances, which in turn can increase reports of anxiety and depressive symptoms. Biopsychosocial and partner factors have a significant influence on middle-aged women's sexuality and depressive disorders, and most antidepressants can have a negative effect on sexual response. Lastly, studies have consistently shown that women with high levels of depressive symptoms are at greater cardiovascular risk and have poorer cognitive function than non-depressed women. At present, a direct relationship between psychiatric symptoms and hormonal changes such as estrogen decrease has not been clearly found. Stress, educational level, ethnicity, socioeconomic factors and partner status may influence the prevalence and clinical course of both menopause symptoms and depressive disorders. Since in many cases depression is a lifelong condition, and is associated with severe comorbid conditions, further studies are needed to improve the early diagnosis of depression; it may be advisable to monitor a woman's mental health during the menopause transition to prevent a depressive disorder having long-term negative consequences.     

A screening study of antidepressant treatment rates and mood symptoms in pregnancy

Summary Study design: As part of a large screening study of perinatal depression, pregnant women were screened for demographic, depression and treatment variables in obstetrics clinics. Women taking antidepressant medication prior to conception were included in the sample as the study aimed to document rates of antidepressant medication use, and relationship to depressive symptomatology.Results: Among women who reported using antidepressant medications within 2 years prior to screening (n = 390, or 11% of all women), 22% reported current use of these medications. Women who reported using antidepressant medications (52%) and those who discontinued them (49%) evidenced elevated depressive symptoms during pregnancy.Conclusions: Both women who discontinue and some who continue antidepressants during pregnancy demonstrate depressive symptoms, suggesting sub-optimal management of both groups. Future studies should carefully assess the adequacy of treatments prescribed as well as the monitoring and adherence of recommended treatments. Full symptom remission should be the goal for antenatal and postnatal depression in order to minimize risk to mother and baby.     

Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study

OBJECTIVE: To characterize patterns of depressed mood during the menopausal transition (MT) in relation to age and MT-related factors and to assess the contribution of factors related to depressed mood at earlier points in the life span. DESIGN: Women (N = 508) were recruited from 1990 to 1992 from multiethnic neighborhoods and followed annually through 2005: 302 met the eligibility criteria for analyses reported here. The Center for Epidemiologic Studies Depression scale (CES-D) and a menstrual calendar were completed annually throughout the study. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide, follicle-stimulating hormone, testosterone, and cortisol. Mixed effects modeling was used to identify changes in CES-D scores over time, including the relationship to age, MT-related factors, and factors related to depression at other points in the life span (postpartum depression/blues, life stress, or family history of clinical depression). RESULTS: Age was modestly and negatively related to CES-D scores, but MT stage alone was not, except that the late MT stage was significantly related to depressed mood. Hot flash activity, life stress, family history of depression, history of "postpartum blues," sexual abuse history, body mass index, and use of antidepressants were also individually related to depressed mood; the hormonal assays and age of entry into and duration of late MT stage were unrelated. CONCLUSIONS: Although women in the late MT stage are vulnerable to depressed mood, factors that account for depressed mood earlier in the life span continue to have an important influence and should be considered in studies of etiology and therapeutics.     

Neuroactive steroids after estrogen exposure in depressed postmenopausal women treated with sertraline and asymptomatic postmenopausal women

Neuroactive steroids (NAS) allopregnanolone (ALLO), Allotetrahydrodeoxycorticosterone (THDOC) and dehydroepiandrosterone (DHEA) are important in the regulation of mood and behavior. Knowledge about these steroids in postmenopausal depression and the effect of estrogen on NAS is lacking. We elected to determine if there were differences in NAS between postmenopausal depressed women and age matched controls. We also investigated the effect of estradiol on NAS in post menopausal depressed women receiving a selective serotonin reuptake inhibitor (SSRI), and in non-depressed postmenopausal controls. As part of a previously published double blind study on estrogen acceleration of antidepressant action, post menopausal women with major depression receiving sertraline and healthy non depressed controls were randomized to transdermal estrogen patch 0.1 mg or placebo. NAS were measured at baseline and after 10 weeks of treatment. Depressed subjects were treated with sertraline 50 mg/day to 100 mg/day for 9 weeks. At the baseline and after treatment ALLO and DHEA were significantly lower in depressed women compared to controls. Although all depressed subjects experienced a positive clinical response, estrogen administration was not associated with changes in NAS in either the depressed or the asymptomatic postmenopausal women. The lower ALLO and DHEA in postmenopausal depressed women suggests that symptoms of depression may be influenced by the synthesis or fluctuation of these NAS. Estradiol exposure did not alter ALLO, DHEA, or THDOC, implying these NAS are unlikely to play a role in any mood changes in post menopausal women given estrogen therapy.     

Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk

OBJECTIVE: To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. METHODS: Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. RESULTS: Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre-bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. CONCLUSIONS: Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder.     

EMAS position statement: Managing the menopause in the context of coronary heart disease

Introduction

Cardiovascular disease (CVD) including coronary heart disease (CHD) and stroke is the most common cause of female death. Premenopausal CHD is very rare but when women enter the menopause the incidence of CHD increases markedly. CHD presents 10 years later in women than in men. The reason is still unclear but the protective effects of estrogens have been suggested.

Aims

To formulate a position statement on the management of menopause women in the context of coronary heart disease.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusions

Based on long term randomized placebo-controlled studies hormone therapy (HT) is not recommended for the primary or secondary prevention of CHD in postmenopausal women. In most countries the only indication for HT is the treatment of menopausal symptoms. Women with known CHD or with many coronary risk factors seeking HT because of troublesome climacteric symptoms should be evaluated for their individual baseline risk of developing breast cancer, venous thromboembolism and CHD recurrence. The same applies to non hormone therapy-based treatments where long term clinical studies are lacking. Risks should be weighed against expected benefit from symptom relief and improved quality of life. The lowest effective estrogen dose should be used during the shortest possible time. Transdermal administration is preferred if risk factors for VTE exist. Different progestogens might differ in their cardiovascular effects. Observational studies suggest that micronized progesterone or dydrogesterone may have a better risk profile than other progestogens with regard to thrombotic risk.     

Transcranial direct current stimulation (tDCS) for depression: Analysis of response using a three-factor structure of the Montgomery–Åsberg depression rating scale

Background

There is growing evidence that transcranial direct current stimulation (tDCS) may be an effective treatment for depression. However, no study to date has profiled the antidepressant effects of tDCS using items or factors on depression symptom severity rating scales. This could potentially provide information about the mechanisms by which tDCS achieves its antidepressant effects and also identify clinical predictors of response.

Methods

The present study analysed scores on the Montgomery–Åsberg depression rating scale (MADRS) from a randomised, sham-controlled trial of tDCS (Loo et al., 2012. British Journal of Psychiatry. 200, 52–59) using a three-factor model of MADRS items (Suzuki et al., 2005. Depression and Anxiety. 21, 95–97) encompassing dysphoria, retardation and vegetative symptoms.

Results

Participants in the active tDCS treatment group showed significant improvement in dysphoria while participants in the sham treatment group did not. While both groups showed improvement in retardation symptoms, improvement was significantly greater in the active tDCS group. Both groups also showed improvement in vegetative symptoms but there were no between-group differences.

Limitations

Further studies with larger sample sizes are warranted to investigate the generalisability of results and whether the MADRS factor structure may change as a result of the specific treatment used.

Conclusions

tDCS appears to be particularly effective in treating dysphoria and retardation, but not vegetative symptoms of depression. This may have implications for selection of types of depression most likely to respond to this treatment.     

Neurodevelopmental outcome for offspring of women treated for antenatal depression: a systematic review

The aim of this systematic review is to appraise existing literature on the effects of treatments for antenatal depression on the neurodevelopment outcomes of the offspring. We conducted a systematic review of the literature to identify studies on different kinds of treatments for antenatal depression (antidepressants and alternative therapies) and their effects on infants’ neurodevelopment. After reading the title, abstract, or full text and applying exclusion criteria, a total of 22 papers were selected. Nineteen papers studied the effects of antidepressant drugs, one on docosahexanoic acid (DHA) (fish oil capsules) and two on massage therapy; however, no studies used a randomized controlled design, and in most studies, the control group comprise healthy women not exposed to depression. Comparisons between newborns exposed to antidepressants in utero with those not exposed showed significant differences in a wide range of neurobehavioral outcomes, although in many cases, these symptoms were transient. Two studies found a slight delay in psychomotor development, and one study found a delay in mental development. Alternative therapies may have some benefits on neurodevelopmental outcomes. Our review suggests that antidepressant treatment may be associated with some neurodevelopmental changes, but we cannot exclude that some of these effects may be due to depression per se.     

Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression

BACKGROUND: Early authors described hypomanic symptoms as mixed features in depressive episode, but this syndrome has not been sufficiently explored in previous studies. METHODS: 958 consecutive depressed patients were assessed by using a standardized method in terms of 43 psychiatric symptoms at hospitalization. RESULTS: A principal component analysis, followed by varimax rotation, extracted six interpretable factors: typical vegetative symptoms, depressive retardation/loss of feeling, hypomanic syndrome, anxiety, psychosis, and depressive mood/hopelessness. The extracted factor structure was relatively stable among several patient groups. There was no evidence that the hypomanic factor was exaggerated by antidepressant pretreatments before hospitalization. Bipolar diagnoses were associated with higher scores on depressive retardation and hypomanic symptoms, and a lower score on anxiety. LIMITATIONS: Psychiatric syndromes and their interrelationships, found in the present study, may be strongly influenced by the rating instrument used. The sample of this study was depressed inpatients. The results should not be generalized for depressed outpatients or epidemiological depressed populations. CONCLUSIONS: Hypomanic symptoms, as characterized by the flight of ideas, racing thought, increased drive, excessive social contact, irritability, and aggression are a salient syndrome in acutely ill depressed patients, lending support to the factor validity of mixed depression. The symptoms may not be related to pretreatments with antidepressants, or comorbidity of substance abuse, suggesting that they reflect various natural phenomenological manifestations of depressive episodes. Anxiety is unlikely to play a major role in the core phenomenological features of mixed depression. Hypomanic symptoms during a depressive episode were more represented in bipolar disorders, which may serve for further clarifications of latent bipolarity in unipolar depression, and prediction of switch into maniform states under biological depression treatments.     

NAMS/Solvay Resident Essay Award. Relationship between estrogen, serotonin, and depression

OBJECTIVE: A limited review of the medical literature was performed to determine whether there is an increase in the prevalence of depressive symptomatology in women undergoing menopause and whether this increase can be related to fluctuating levels of estrogen. In addition, we evaluate the possible effect that estrogen has on the concentrations of neurotransmitters, specifically serotonin, in the central nervous system and the subsequent impact on mood in peri- and postmenopausal women. Finally, we examine whether estrogen replacement therapy is efficacious in the treatment of depression during the climacteric. DESIGN: Limited MEDLINE review of the medical literature on depression in women, the evidence for a serotonergic role in depression, evidence linking estrogen to changes in serotonergic activity and evidence that estrogen therapy can improve depression. RESULTS: Depression is more common in women than in men and seems to be increased at times of changing hormone levels in women. The serotonergic system seems to play a major role in depression, although other neurotransmitters are also involved. Estrogen can alter not just serotonergic activity but also has an impact on the activity of several other neurotransmitters that might result in an antidepressant effect. At this time, estrogen therapy for the treatment of depression in peri- and postmenopausal women may be useful, but confirmatory studies are still lacking. CONCLUSIONS: There is suggestive evidence that estrogen therapy is appropriate treatment for mid-to-moderate depression in peri- and postmenopausal women.     

Does body fat protect against negative moods in women?

An examination of the relationship between body mass index (BMI) and negative mood revealed an inverse relationship between BMI and negative mood symptoms (i.e., depression and negative affect scale scores) in women who were not taking oral contraceptives. The strength of the negative correlations between BMI and negative affect was uniformly higher on days of the menstrual cycle when estrogen levels are expected to be highest. Two interpretations are suggested. Given the positive relationship between estrogen levels and body fat, estrogen may have an effect on both body fat storage and negative affect. The cyclical release of estrogen may also have activational effects on negative affect. These findings have implications for common beliefs about the relationship between body size and emotional well-being, and provide converging evidence for the role of hormones in the regulation of mood.     

The impact of depression and fluoxetine treatment on obstetrical outcome

Summary Introduction: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome.Method: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit.Results: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression.Conclusions: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.     

Neurophysiologic changes during estrogen augmentation in perimenopausal depression

BACKGROUND: Estrogen augmentation of antidepressant medication has been an effective treatment in a subgroup of women experiencing affective symptoms during perimenopause. It has been suggested that estrogen facilitates serotonergic transmission in brain regions involved in mood disorders. We investigated differences in physiologic brain changes with estrogen augmentation in women with perimenopausal depression who reached remission compared to those who did not reach remission. We also assessed whether such changes were correlated with serum hormone levels. METHODS: Quantitative electroencephalography (QEEG) was used to examine neurophysiologic brain changes in remission and non-remission of depressive symptoms. Women with major depressive disorder (MDD) in partial remission who were taking antidepressant medication for a minimum of 8 weeks and were experiencing two or more perimenopausal symptoms (hot flashes, night sweats, irregular periods, memory impairment, vaginal dryness) were recruited from the community. Absolute power, relative power, and QEEG cordance, a measure that has moderately strong associations with cerebral perfusion, were obtained before and after 6 weeks of treatment with 0.625 mg of conjugated estrogen per day. RESULTS: Women who experienced remission of depressive symptoms (Ham-D< or =7) had a significant decrease in right frontal QEEG cordance (p=0.008, t((8))=-3.54) which was not present in non-remitters. No significant correlations were found between hormone levels and QEEG cordance. CONCLUSION: In women with perimenopausal depression, physiologic brain changes in the right frontal region during estrogen augmentation were associated with remission of depression.     

A prospective,randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms,psychological well being,and quality of life in postmenopausal Chinese women

OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.