Psychiatric considerations in menopause
Women’s risk of psychiatric symptoms and disorders is increased during menopause.
Role of estrogen on mood and psychosis
Women are at higher risk throughout their reproductive life than are men for MDD, anxiety disorders, and trauma-related disorders.12 Factors associated with depression during the menopause transition are reproductive hormonal changes (rise of follicle-stimulating hormone [FSH] and luteinizing hormone levels, and variability in estrogen [E2] and FSH levels); menopausal symptoms, particularly vasomotor symptoms; prior depression; psychosocial factors (adverse life events, financial strain, poor social supports); high body mass index, smoking, and poor physical health.6,7 Decreasing estrogen in the menopause transition may increase susceptibility to depression in some women.16 The Box17,18 provides more information on the relationship between estrogen and brain function.
Box
Estrogen and brain function
Numerous molecular and clinical studies have established the role of 17-beta estradiol in modulating brain functions via alterations in neurotransmission.17 Estrogen increases serotonin availability in the synapse by various pathways. It increases the rate of degradation of monoamine oxidase; monoamine oxidase enzymes are responsible for catabolizing serotonin, dopamine, and norepinephrine. Estrogen also increases tryptophan hydroxylase expression (rate-limiting enzyme in serotonin synthesis) and promotes intraneuronal serotonin transport in brain regions associated with affect regulation by increasing gene expression of the serotonin reuptake transporter. Studies have linked brain-derived neurotropic factor (BDNF) to increased serotonin turnover and proposed that estrogen may influence depression by increasing BDNF levels within the brain.18
Depressive disorders, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression, have been linked to changes in hormonal status in women. Symptomatic menopause transition occurs in at least 20% of women, and a retrospective cohort study suggests that symptomatic menopause transition might increase the risk of new-onset depressive disorders, bipolar disorders, anxiety disorders, and sleep disorders.19 Symptomatic menopause transition also is a vulnerable time for relapse of MDD. Among women experiencing menopausal symptoms, including hot flashes, one-third also report depression—which correlates with a poorer quality of life, less work productivity, and greater use of health care services.9
Women who undergo surgical menopause are at greater risk for depression.8,10,11 This may be due to abrupt deprivation of estrogen—or related to a psychological reaction to the loss of fertility.
The observation that hormonal fluctuations related to women’s reproductive cycle have a significant impact on psychotic symptomatology has resulted in the “hypo-estrogenism hypothesis,” which proposes that gonadal dysfunction may increase vulnerability to schizophrenia, or that schizophrenia may lead to gonadal dysfunction.20 The “estrogen protection hypothesis” proposes that estrogen may protect women from schizophrenia, and may be a factor in the delayed onset of schizophrenia compared with men, less severe psychopathology, better outcomes, and premenstrual and postmenopausal deterioration in women. Many women of reproductive age with schizophrenia experience improvement in symptoms during the high estrogen phase of their menstrual cycle.
Pope et al21 have suggested that a hormone sensitivity syndrome may underlie why some women experience physical, psychological, and emotional symptoms at times of hormonal shifts such as menopause. This may represent a critical window of vulnerability, and also an opportunity to consider E2 as a therapeutic intervention.
Continued to: Treating mental illness in menopause
