Mental health around and after the menopause

Introduction

The menopause is a time of many changes, with physical, psychological and social significance for a woman, as summarized in Box 1. Menopause represents a significant life transition with profound biological consequences, but it is a physiological event and not an illness. While most women traverse the menopausal transition (MT) with little difficulty, others may undergo significant stress. And with increasing age, emerging physical health problems can cause significant changes in the woman's lifestyle, leading to social withdrawal, avoidance and curtailment of physical activity. Changes in social circumstances related to work and family during midlife also have an impact on women's emotional wellbeing. Alterations in family roles and interpersonal losses combined with a sense of ageing may cause psychological symptoms. As well as the psychosocial changes at this time of life, there is considerable evidence that reproductive hormones, especially estrogen, may have effects upon mood (see Box 2 for summary), so it is at least plausible that failure of estrogen production may be linked to mood changes.

In this paper, we review the existing literature on this subject to identify the extent of mental health problems in women in MT, in particular the relationship between depression and menopause. We also discuss the assessment and management of depression, and we also consider depression after the menopause and into old age.

Psychological symptoms in the MT

Population-based studies show that self-reported symptoms attributed to menopause are common in women aged 45–54, but these are often not perceived as a problem. ¹ Women experiencing an early natural menopause have a raised risk of vasomotor symptoms, sexual difficulties and trouble sleeping. However, there is little or no excess risk of other somatic or psychological symptoms. ² Avis et al. ³ examined health-related quality of life (HRQL) during the MT in a prospective longitudinal study (the Study of Women's Health across the Nation; SWAN study) and found that there was little impact of MT on HRQL when adjusted for symptoms, medical conditions and stress. The Women's International Study of Health and Sexuality (WISHeS) study ⁴ evaluated pre- and postmenopausal women regarding their experience with sexual desire. The prevalence of hypoactive sexual desire disorder (HSDD) ranged from 9% in naturally postmenopausal women to 26% in younger surgically postmenopausal women. The women classified as having HSDD were significantly more likely than those with normal sexual desire, to agree with statements expressing negative emotional states. Another prospective study, the Melbourne Women's Mid-Life Health Project, reported increased symptoms of depressed mood during this phase. ⁵ One particular finding from this study was a lack of evidence for the so-called ‘empty nest syndrome’: indeed most women experience a sense of liberation when their adult children leave home. ⁶

Does the menopause cause depression?

Thus there is evidence that some women experience psychological symptoms during the time of menopause, and it is plausible that decreased estrogen production may be associated with depression. But does the menopause actually cause depression? There have been conflicting findings and considerable controversy over this issue. Earlier studies were cross-sectional in design and could not really answer this question. More recent evidence comes from several longitudinal studies.

Causes of uncertainty include the overlap between menopausal and depressive symptoms, e.g. loss of energy, sleep disturbance, weight change, poor concentration, decreased libido. Also, the main determinants of being depressed during the menopause are other factors, such as previous history of depression, social and relationship problems, substance misuse, etc. This is also true of wellbeing (Seattle study), ⁷ which is related to a sense of mastery and satisfaction with social support, and decreased by adverse life events, but it does not appear to be related to any hormonal markers of MT.

Moreover, even if the menopause causes women to experience increased rates of depression, is this related at all to hormone levels or is it due to psychological factors such as a perception of loss of womanhood?

These are not easy questions to determine. They require longitudinal samples, and to investigate hormonal changes, blood samples are needed too. The typical approach requires a comparison among women with no prior history of depression at different points in the perimenopause.

Even so, the findings remain diverse. Freeman et al. ⁸ studied 231 women who had no previous depression. Of these, 116 developed depressive symptoms during the follow-up period; 108 did not. Between the two groups, high CES-D (Centre for Epidemiological Studies Depression Scale) scores were four times more likely during the MT than before and the risk of having a diagnosis of depression was doubled. Greater variability in levels of estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels was also associated with depressive symptoms. Other factors that were associated with depression were loss of employment/partner, history of severe premenstrual syndrome, smoking, hot flashes and increased body mass.

Published alongside this paper was the study of Cohen et al., ⁹ reporting data from the Harvard Study of Moods and Cycles. They studied women aged 36–45, with no previous depression. After six years, the perimenopausal group was twice as likely to have had a first onset of depression during the study period: there was a slightly increased risk with self-reported vasomotor symptoms. However other factors, such as the presence of vasomotor symptoms, use of hormone therapy and adverse life events, independently modified this risk.

Data from the SWAN study ¹⁰ of over 3000 women suggested that testosterone was independently associated with higher levels of depressive symptoms, although this was a relatively small effect compared with other variables such as menopausal status or adverse life events. About 30% reported feeling irritable, blue and nervous during the menopause compared with 20% of premenopausal women. Also this study assessed diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. ¹¹ Women were two to four times more likely to experience a major depressive episode when they were perimenopausal or early postmenopausal. Previous history of major depression was a strong predictor of major depression.

The Seattle study ¹² investigated various patterns of depressed mood in women during different stages of MT in relation to age and MT-related factors. Five hundred and eight women were recruited from multiethnic neighbourhoods and the CES-D plus a menstrual calendar were completed annually during follow-up. Changes in CES-D scores over time were analysed in 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). The majority of women experienced MT without a high severity of depressed mood while a small group of women had mood worsening over time and others improved. Age was modestly and negatively related to CES-D scores, but MT stage alone was not 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 all individually related to depressed mood. This suggests although women in the late MT stage are vulnerable to depressed mood, factors that account for depressed mood earlier in life, such as previous depression, social problems, substance misuse, etc. continue to have an important influence.

Relationship between depression and other menopausal symptoms

There is some evidence that depression is more likely alongside troublesome hot flashes and that this is associated with fluctuating hormone levels. Freeman et al. ¹³ evaluated this association and found that reporting of both hot flashes and depressed mood was greater than expected if the processes operated independently. In the Seattle study, ¹⁴ women who reported high stress levels of sleep disturbances, increased fatigue, anxiety, depressed mood and hot flashes also reported less sexual desire. It appears that depressive symptoms not only overlap with several of the physical symptoms attributed to menopause but also occur simultaneously. Whether the depression contributes to greater hormonal fluctuation or the depression arises from distressing physical symptoms, or whether the two simply result from a common cause in the central control of mood and endocrine function is open for debate.

Does depression affect the menopause?

Being depressed affects all aspects of life and is likely to make any physical symptoms more prominent, especially if there is also sleep disturbance. The cognitive distortions in depression can lead a person to maximize their problems, seeking medical help more than usual. A depressed woman lacks energy and engages in less physical activity, thereby having longer periods to ruminate about her current state.

Having a past history of depression may be associated with an earlier MT especially in women with significant current depressive symptoms. ¹⁵ The Harvard Study of Moods and Cycles is a population-based prospective study of premenopausal women with and without a lifetime history of major depression. This examined the association between lifetime history of major depression and the decline in ovarian function. The study included prospective documentation of menstrual cycle changes and new onset psychiatric morbidity over time, as women approached the MT. Depressed women had 1.2 times the risk of entering perimenopause when compared with those who had no such history. Women with severe depressive symptoms had twice the risk, and among those, the group that had used antidepressants had thrice the risk of developing early perimenopause when compared with those without depressive symptoms. Women with a history of depression also had higher FSH and LH levels suggesting that depression has an effect on the hypothalamic–pituitary–gonadal axis. Therefore, a history of depression appears to be associated with earlier decline in ovarian function.

Depression in postmenopausal women and depression in later life

The course of depression during the menopause is not much studied beyond its onset. There is a lack of information on the course and outcome for women who experienced their first episode of depression during the menopause. Though there is no evidence to suggest that the symptoms of depression during menopause are any different from those occurring earlier in life, the WISHeS study ⁴ indicated that there were three groups of menopausal symptoms, with different courses and correlates. The first group was related to declining estradiol, including vasomotor symptoms, poor memory, sleep problems, head/neck/shoulder aches, vaginal dryness and diminished sexual arousal. These symptoms peaked at about age 50 and then declined. The second group of symptoms was psychological which peaked at age 35–40 or during the early MT period and decreased afterwards albeit influenced by physical health. The third cluster, including decreased physical strength and energy, was regarded as the effects of ageing, and was affected by other health measures and body mass index. The MT phase also amplified the negative mood effects of other adverse life events. Surgically induced menopause was associated with a greater risk of depression, perhaps because of its abruptness, the context of the surgery and the more profound hormonal alterations that result.

There is no particular reason to suppose that depression in menopause follows a different course compared with depression experienced earlier. However, it is useful to consider some facts concerning late onset depression compared with depression in early years of life. These factors will be important when assessing a woman in menstrual transition, for depression at more advanced ages has certain distinguishing characteristics. When people with depression at different ages are compared, physical health complaints such as pain, dizziness and hypochondriacal preoccupations are significantly commoner in older people. ¹⁶ Also psychotic symptoms are seen commonly in older people with depression ¹⁷ but this is not universal. The higher rates of depression in women begin to converge with those of men in old age – though, as women survive longer, the majority of older people who are depressed are women. When women who had their first onset of depression relatively young are compared with those with onset after the menopause, there is more evidence of family history in younger onset cases suggesting greater genetic loading. ¹⁸ Physical pathology, especially small vessel cerebrovascular disease, is commoner in late-onset cases. ¹⁹

With advancing age, depression and physical health are interwoven in many ways. ²⁰ The menopause and its associated consequences are no exception to this. Depression may be precipitated by physical illness especially those which are chronic. Neurological illnesses such as stroke or Parkinson's disease are strongly associated with depression. Also the physical health symptoms are often magnified in depression complicating the management, for example poor diabetic control or increased pain perception. Medications commonly used, e.g. antihypertensives, can themselves cause depression. Depression often makes individuals more susceptible to poor health, due to coexisting alcoholism or smoking. The presence of a co-morbid chronic physical illness may limit the selection of antidepressants or limit the maximum doses that can be used. Also the presence of physical co-morbidity increases the likelihood of drug interactions. Finally, physical illness determines the outcome of depressive episodes in older people. It leads to longer episodes and less complete remission of symptoms. Physical illness is also a major cause of relapse of depression. There is also increased mortality associated with depression, mainly due to cardiovascular risk disease.

Assessment and diagnosis of depression

This may be quite challenging, considering the overlap of symptoms between depression and the menopause itself. It is much commoner to have subsyndromal depressive symptoms rather than the full picture of major depression. Symptoms associated with depression include fatigue, loss of energy, loss of interests, poor concentration, altered sleep patterns pessimistic views of future. However these are non-specific and can also be due to physical illhealth or simply getting older. Therefore the extent to which older people are depressed may be overestimated.

The central feature of depression is low mood, which may be persistent but often fluctuates, sometimes with a pattern of diurnal variation. Alongside this is anhedonia, an inability to enjoy activities that would normally bring pleasure. There may be other mood changes too, such as anxiety and even panic, or irritability. Alongside the low mood go various gloomy thoughts lack of self-worth, self-criticism, and feelings of failure, futility and hopelessness. Obviously it is important to enquire after thoughts of self-harm or suicide. The diagnosis of a depressive disorder requires the core features of low mood along with negative thoughts and/or biological symptoms. Most depression in primary care is mild to moderate in severity but occasionally depression is very severe and may be associated with delusions, e.g. of guilt, poverty or terminal illness.

There is no evidence that depressive disorders become commoner with increasing age. Studies comparing the outcome of depression in different age groups indicate that symptoms improve equally well in older people but they are more liable to relapse. ²¹ Though several rating scales (e.g. Beck's depression inventory, Hamilton depression scale) exist to assist in diagnosing and assessing the course of depression, a structured diagnostic interview is the most reliable method to diagnose mood disorder.

Treatment of depression during and after the menopause

Treatment of depression in older people

The effects of age-related changes in the pharmacodynamics and pharmacokinetics combined with poor physical health determine varied responses to medication. There is an increased risk of side-effects plus drug interactions necessitating the use of smaller doses, gradual dose increments and cautious strategies for combination of medications. Regarding treatment maintenance, in younger groups, the recommendation is to continue antidepressants for 6–12 months from the point of remission. Since older women may be more liable to relapse continuing treatment for a longer period, say two years, may be more appropriate.

Cognitive impairment related to the menopause

Slight changes in memory and processing speed are evident during the MT, and physiological factors associated with hot flashes may contribute to this. ³⁷ In the Seattle Midlife study, MT-related factors were not found to be significantly associated with difficulty in concentrating or forgetfulness. ³⁸ In fact, the best predictors of forgetfulness were age, hot flushes, anxiety, depressed mood, perceived stress, perceived health and history of sexual abuse. Memory problems were mostly related to lower ratings of health and depressed mood. Therefore there is no suggestion that cognitive complaints are related to the early development of dementia.

Theoretically, estrogen might prove an effective neuroprotective agent for dementia, but this has not been borne out. Indeed from a recent Cochrane review, ³⁹ there is good evidence for hormone therapy not being useful in cognitive decline in older postmenopausal women. Whether the absence or presence of menopausal symptoms can modify treatment effects needs further investigations. It concludes that hormone therapy cannot be recommended for overall cognitive improvement.

Conclusions

Most women pass through the MT without major mental health problems. For those women who are vulnerable to depression, the perimenopausal period does appear to be a time of increased risk, even for those who have not previously been depressed. Recent long-term, prospective studies have demonstrated this. A number of biological and hormonal factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues. However, the most important contributory factors to depression in this stage of life are the usual factors, i.e. previous depression, psychosocial and relationship problems, and substance misuse: not solely the hormonal changes.

Both during and beyond the menopause, depression is a major health issue for women. The identification of individuals whom might be at a higher risk for depression during MT could guide preventive strategies for this population. Treatment options will include controlling the symptoms associated with menopause and antidepressants in women who display clinical depression. There are some distinct features of depression to be considered in older women, and the effects of other health problems, especially chronic physical illnesses and dementia, become more important with increasing age.

Competing interests

TD acknowledges the support of the National Institute for Health Research (NIHR) Collaboration for Applied Health Research and Care based in Cambridgeshire and Peterborough.