The hormonal changes that accompany the transition to menopause are disruptive to most women, and for some, mental health maybe adversely affected. Depressive symptoms and major depression are the best-studied conditions in association with menopause, but anxiety, executive function, and comorbid pre-existing psychiatric conditions all influence the symptomatology that women will experience during this phase of their lives. The epidemiology, diagnosis, and evidence-based treatment guidelines for perimenopausal patients are discussed.
Key points
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The menopausal transition is a window of vulnerability for women’s mental health.
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New onset and recurrent depression, as well as anxiety, increase concurrent with progression through menopause.
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Aspects of cognition, including memory and attention, may also be compromised during the menopause transition.
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Trauma exposures and traumatic stress symptoms are common among midlife women and are associated with an increased risk for menopausal symptoms.
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Principles of treatment are similar to other stages of life, with the exception of a possible role for estrogen as an adjunct in attenuating the course of perimenopausal depression.
Introduction
Mental health is important at every stage of life and interacts with how an individual responds to stress. It is critical to attend to mental health during a woman’s menopausal years, because most women are likely to experience some degree of disruption and decreased well-being from menopausal symptoms, which may exacerbate pre-existing or create new mental health issues. This review discusses the prevalence of mental health challenges during menopause and their close relationship with physical symptoms and social determinants of health as risk factors. Screening for key risks, especially adverse life events, is encouraged. Finally, approaches to treatment of women struggling with a loss of well-being at this life stage will be discussed. In this article, the word “woman” refers to individuals who are assigned female at birth and who have functioning ovaries in adulthood. Race and ethnicity, unless otherwise mentioned, was assessed by self-report in cited studies.
Discussion
Epidemiology and Statement of the Problem
Depressive disorders
Depression is among the 3 most common worldwide causes of years lived with disability. In 2020, among US adults aged 45 to 64 years, 18.4% reported having ever received a diagnosis of depression by a health care provider. Women report depression about twice as frequently as men. , Unlike men, women are regularly exposed to wide hormone fluctuations across the menstrual cycle—approximately a 10 fold for estradiol and almost a 1000 fold for progesterone. Both estradiol and progesterone and its metabolites are neuroactive steroids with receptors throughout the body. They, therefore, have the potential to impact mood on a number of different levels, and indeed, women appear to develop new or recurrent mood disorders at times of sex steroid flux: puberty, pregnancy and postpartum, and the menopausal transition.
Association of the menopausal transition with increased depressive symptoms and major depression is supported by 3 longitudinal studies. Cohen and colleagues, in the Harvard Study of Moods and Cycles, examined 460 mostly White women with no prior history of major depression from the Boston area for up to 10 years. They noted that the risk of major depression doubled in women who had progressed into their menopausal transition versus those who did not, as defined by changes in cycle regularity or menstrual flow. Freeman and colleagues, in the Penn Ovarian Aging Study, observed 231 Black and White women with no prior history of major depression over 8 years. Again, they found a marked increase in both clinically significant depressive symptoms (almost 4 fold), as assessed by the Center for Epidemiologic Studies-Depression (CES-D) scale (score of ≥16) and major depressive disorder (MDD; 2.5 fold) as assessed by the Primary Care Evaluation of Mental Disorders or Patient-Health Questionnaire (PHQ-9) scales in association with entry into the menopausal transition relative to premenopause. This group found that up to 50% of the sample reported increased clinically significant depressive symptoms (CES-D score ≥16) and 26% met criteria for depressive disorder in association with their menopausal transition. The estimates of an increased risk for new-onset MDD among individuals without a previous major depressive episode (MDE) are in close agreement between the Harvard Study of Moods and Cycles and the Penn Ovarian Aging Study. Finally, the Study of Women’s Health Across the Nation (SWAN) assessed 3302 women over 5 years. The prevalence of elevated CES-D scores (≥16) was 23% at baseline, and the odds ratio for reporting high CES-D scores (≥16) associated with entry into the menopause transition compared to premenopause ranged from 1.3 to 1.7 depending upon menopause stage and hormone therapy (HT) use. Women with lower CES-D scores at baseline were slightly more likely to develop high CES-D scores (≥16) during the follow-up period. SWAN also followed a subset of 77 Black and 101 White women for 10 years, conducting assessments annually for the development of MDD using the Structured Clinical Interview for DSM Disorders. They observed a 2 to 4 fold increased risk for MDD associated with the menopausal transition. All 3 longitudinal studies indicate a clear trend for greater risk of high depressive symptoms as well as MDD in association with the menopausal transition ( Table 1 ), with remarkable agreement across study populations.
| References | N | CES-D >16 (%) | CES-D>16 (OR) | MDD (%) | MDD (OR) |
|---|---|---|---|---|---|
| Cohen et al, 2006 | 460 | 32.5 | 1.8 [1.0,3.2] | 16.6 | — |
| Freeman et al, 2006 | 231 | 50 | 4.29 [2.39,7.72] | 26 | 2.5 [1.25, 5.02] |
| Bromberger et al, 2011 Bromberger et al, 2007 | 221 3302 | 23 | 1.3–1.71 b | 23.8 | 1.98–3.86 a |
a OR for CES-D >16 from premenopausal to early menopausal transition = 1.98 [1.0,3.92]; OR for premenopausal to postmenopausal = 3.86 [1.39, 10.92].
b OR for premenopausal to early menopausal transition 1.3 [1.09, 1.55], OR for premenopausal to late transition = 1.71 [1.27, 2.30], OR for premenopausal to postmenopausal = 1.57 [1.15, 2.15].
Risk factors for depression
Women at highest risk for MDD are those with a history of depression. In clinical practice, these patients are more likely to be able to articulate their symptoms and their meaning. However, somewhat surprisingly, women with low depressive symptoms at the onset of the menopause transition are also likely to develop MDD. In these patients with no prior history of depression, symptoms may be far more difficult to identify, especially if they are concurrent with other, bothersome menopausal symptoms. The Harvard Study of Moods and Cycles found that adverse life events in the past 6 months increased the risk for developing an MDE during the transition to menopause. In the Freeman study, higher baseline CES-D scores were predictive of later worsening CES-D scores of 16 or greater. Variability (and not absolute levels) of estradiol; variability and high follicle-stimulating hormone; and vasomotor symptoms (VMS) were associated with both high CES-D scores of 16 or greater and occurrence of depressive disorder. This group also found that participants were less likely to report severe premenstrual syndrome-type symptoms while reporting higher depressive symptoms (CES-D ≥16) relative to before reporting higher depressive symptoms. Body mass index increases were associated with an increased risk for higher depressive symptom severity (CES-D ≥16) and MDD. In the SWAN study, current and former hormone use was associated with greater risk for depressive symptoms.
Anxiety
Anxiety disorders are the most common mental illnesses in the world, with evidence of substantial increases in prevalence since 1990 and a sex ratio of 1.36 favoring women. Anxiety disorders peak in incidence in adolescence and early adulthood and tend to decrease over the age of 60 years. Patterns of anxiety are similar to those of depression in association with the menopause transition; however, there are key differences. Bromberger reported on the prevalence of anxiety in 2956 women from multiple racial and ethnic groups in the SWAN study. A high anxiety score was considered any score greater than 4 based on frequency of 4 anxiety symptoms over the prior 2 weeks. Women with low anxiety scores at baseline were more likely to develop high anxiety during the menopausal transition including through early postmenopause (odds ratio 1.56–1.61). Women with high anxiety at baseline tended to continue to have high anxiety symptoms throughout their menopausal transition, with no difference by menopausal stage. This pattern of anxiety onset is in contrast to that of depression and depressive symptoms. In the case of depression, women with a prior history of depression were more likely to have an episode of MDD during their menopause transition, although new cases of MDD were also detected. The new onset of anxiety symptoms in women with low initial anxiety scores calls for increased clinical vigilance to detect the new onset of high anxiety and refer for treatment before it becomes disabling. VMS were associated with high anxiety in the SWAN sample and the Penn Ovarian Aging Study.
Traumatic stress disorders
Posttraumatic stress disorder (PTSD) describes a psychiatric illness that develops in response to a traumatic event or events. Evidence indicates that PTSD symptoms and trauma exposure are common among midlife women. One large-scale study revealed that over 22% of midlife and older women had clinically significant PTSD symptoms, with similar percentages endorsing lifetime emotional interpersonal violence (21%), lifetime physical interpersonal violence (15%), and sexual assault (18%). Women experiencing PTSD symptoms had higher odds of experiencing menopause symptoms, including sleeping difficulties (odds ratio 3.02), hot flashes (odds ratio 1.69), night sweats (odds ratio 1.72), and pain with intercourse (odds ratio 2.16). Moreover, women who have experienced trauma are at an increased risk for other psychiatric comorbidities including MDD; approximately half of people with PTSD also having a diagnosis of MDD.
Cognition and attention deficit disorders
The menopause transition is associated with changes in sleep and mood, which can in turn affect cognition. Independent effects of menopause on specific aspects of cognitive function, particularly verbal learning and memory and attention, have been described in longitudinal studies. Natural menopause is associated with transient, accelerated reductions in certain aspects of working memory, such as word recall; after a woman has gone for a year without menses and is declared menopausal, memory and other cognitive processes follow a curve of decline that is age related. Women who are in perimenopause and women who have undergone surgical menopause endorse more difficulty with executive functions including initiating and sustaining focus on tasks; processing speed; motivation for work; and working memory relative to those in premenopause. The proportion of women who are affected and who might benefit from treatment are not well known at this time. Women with known attention deficit disorders may well worsen during the menopause transition, but prevalence data are lacking.
Other mental health issues
Bipolar disease, schizophrenia, and schizoaffective disorders are present in about 1% of the population, with the first being more prevalent in men than in women and the last 2 with equal prevalence by sex. Data are scarce on specific associations of the menopause transition with schizophrenia and schizoaffective disorders; however, the disruptive nature of menopausal symptoms is likely to exacerbate the underlying chronic condition, and limited evidence suggests that hallucinations and delusions worsen as women approach menopause and that medication dosages may require adjustment. Bipolar disease may also be exacerbated by menopause and concurrent mood disturbances due to hormonal fluctuations.
Assessing Mental Well-being during the Menopausal Transition
Gynecologists are well-placed to detect depression and other mental health disorder symptoms and to initiate or refer to treatment. Many women consider their gynecologist as their primary care provider; similarly, almost 50% of obstetrician–gynecologists (OB/GYN) also consider themselves as primary care providers. In many cases, women see their gynecologist throughout their reproductive, menopause transition, and postmenopause years for treatment. Many women confide with their OB/GYN about a variety of health care issues including emotional ones. In the case of long-standing patient relationships, OB/GYNs can detect changes in their patients’ emotional health and well-being from visit to visit and with an evidence-based, trauma-informed approach can be both confident and sensitive about asking about trauma.
Assessment of mental health symptoms during the menopausal transition
Preventive measures have the highest chance of succeeding when delivered at routine intervals (eg, at the annual gynecologic examination) and at “critical periods” or “windows of vulnerability,” specific periods along the life course when adverse events or exposures have the greatest negative impact. During the menopausal transition, vulnerability may exist in each stage as reproductive hormone levels and psychosocial circumstances are in flux; evidence reviewed earlier indicates that the menopause transition is associated with an increased risk for depression, for example. Windows of vulnerability, when appropriately identified, provide opportunities for prevention. Gynecologists have substantial influence in reducing the impact of mental health issues by identifying, providing psychoeducation, and initiating treatment or providing referrals for depression, anxiety, and trauma symptoms throughout the menopause transition.
Depressive disorders
Screening for depression can include a commonly used, validated tool for the assessment of depressive symptoms—such as the 9 item PHQ-9 —and it may be integrated into many electronic health records. These self-report questionnaires are typically easy for patients to complete in the office or prior to the visit. The PHQ-9 includes questions about each of the 9 criteria used to make a depression diagnosis in the American Psychiatric Association’s Diagnostic and Statistical Manual for Mental Disorders. Scoring on the PHQ-9 differentiates among a range of minimal-to-severe depressive symptoms. A thorough clinical assessment and diagnostic interview by a psychologist are necessary when the screening/provisional diagnosis meets criteria for moderate-to-severe depressive severity. Box 1 provides the diagnostic criteria for MDD. Perimenopausal women may present with atypical depressive symptoms—such as increased sleep disturbances or increased weight gain and appetite—and this should be considered in the differential diagnosis.
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Low mood observed by self or others
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Loss of interest in most activities observed by self or others
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Significant and unintentional weight change
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Sleeping too much or trouble falling or staying asleep
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Moving significantly more quickly or slowly than is typical
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Noticeable lack of energy
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Feelings of worthlessness or unwarranted guilt
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Trouble thinking, concentrating, or making decisions
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Thinking about death, desiring to be dead, planning or attempting to kill oneself
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Aches or pains, headaches, cramps, or digestive problems without clear etiology
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Poor personal hygiene
For diagnostic and statistical manual of mental disorders, 5th edition (DSM-5) diagnostic criteria of Major Depressive Disorder, see reference.
Anxiety
A self-administered, well-validated screening tool for anxiety, such as the Generalized Anxiety Disorder 2-item (GAD-2), adds valuable information to the assessment process. GAD shows higher comorbidity with other mental disorders like depression and somatization. The GAD-2 is a quick 2 item self-assessment that screens for generalized anxiety disorder (GAD). A cutoff score of 3 is recommended to identify possible cases of GAD. This GAD-2 cutoff score may also be used to identify cases of other anxiety disorders, including panic and social anxiety disorder, but this has not yet been well-validated.
Traumatic stress disorders and use of a trauma-informed approach
A number of presenting problems may be related to a history of abuse (eg, chronic pelvic pain, sexual dysfunction, substance use disorders, obesity, and chronic diseases). Knowledge of abuse history via history taking and screening may assist with treatment planning and the delivery of trauma-informed care. The American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women states that OB/GYNs ought to familiarize themselves with and strive to implement a trauma-informed approach across all levels of their practice. Mounting evidence has shown that a patient-centered, trauma-informed approach to communicating and relating with trauma survivors enhances their mental health treatment and increases the likelihood of treatment success. It promotes attention to the doctor–patient partnership, respect for the patient’s values and preferences, in addition to awareness that traumas can be reactivated or activated in medical settings. Indeed, untreated trauma may create more physical complaints (somatization), leading to more clinician visits, potential noncompliance with treatment, and less trust of medical professionals. ,
Within a trauma-informed context, a variety of expert opinions exist regarding best practices for trauma screening. Some advocate for universal and upfront screening, whereas others support later screening for trauma after trust is built with clinicians (Center for Health Care Strategies). Clinicians should consider the most appropriate way to screen for trauma and the services they can provide at their specific practice. Practices ought to consider the choice of screening instrument, the timing of screening, whether screening will include current or past trauma, and method of delivery (ie, self-completion or face-to-face). Another important consideration relevant to trauma-informed approach is containment: asking about the level of detail of trauma history that preserves the patient’s emotional and physical safety, stays mindful of the time frame of clinician’s interactions with patients, and allows for clinicians to offer patients further treatment. Regarding assessment of current PTSD symptoms, the 20 item PCL-C (civilian version) is a well-validated questionnaire that is easy to administer and score. Because trauma-specific services are typically not provided by OB/GYNs, it is necessary to provide patients with a comprehensive resource list for trauma-specific services and educational materials in order to better facilitate referrals and healing. When menopausal transitions are complicated by issues such as trauma, the need for sensitive, collaborative care between Psychology and Gynecology becomes particularly critical.
Cognitive complaints
Clinicians should address memory concerns among their patients when patients have trouble with orientation (ie, person, place, and time), answering questions or maintaining conversation, and/or may appear to be having other observed significant memory difficulties (eg, getting lost and having trouble recalling details concerning their medical treatment). These issues may suggest cognitive difficulty beyond what is expected due to perimenopause and such patients should be referred for formal evaluation of cognitive performance. In general, patients should be advised that cognitive complaints are probably due to the menopausal transition associated with a subtle and transient cognitive decline. Women with early menopause or those undergoing surgical or chemotherapy-induced menopause should have a lower clinical threshold of suspicion for ordering formal cognitive assessment, since these characteristics are more strongly associated with worse cognitive outcomes.
Treatment of Mental Health Disorders during the Menopause Transition
Depression
MDD is a serious condition requiring expedient and comprehensive treatment—during all phases of life, including the menopause transition. Goals are to reduce depressive symptom severity, prevent recurrence of a depressive episode, and to restore functioning in everyday life. Trials of treatments for MDD among perimenopausal samples provide valuable insights, building upon a larger evidence base from MDD treatment trials among more general samples with MDD. Important factors to consider that differentiate courses for MDD treatment during the menopause transition include (1) determining whether the depressive episode is recurrent (ie, has the patient has experienced an MDE premenopausally) or new-onset (ie, the patient meets diagnostic criteria for MDD for the first time during the menopause transition) and (2) the stage in the menopause transition. Fig. 1 illustrates an evidence-based, potential algorithm to help guide treatment decisions considering the patient’s history and preferences.
