Clinical Review

2019 Update on menopause

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Certain factors are associated with higher risk for depression

The perimenopause represents a time of increased risk for depressive symptoms and major depressive disorder (MDD), even in women with no prior history of depression. Several characteristics and health factors are associated with the increased risk during the menopause transition. These include a prior history of MDD, current antidepressant use, anxiety, premenstrual depressive symptoms, African American race, high body mass index, younger age, social isolation, upsetting life events, and menopausal sleep disturbances.

Although data are inconclusive on whether surgical menopause increases or decreases the risk for developing depression compared with women who transition through menopause naturally, recent studies show an elevated risk of depression in women following hysterectomy with and without oophorectomy.6,7

Menopausal and depressive symptoms can overlap

Midlife depression presents with classic depressive symptoms that commonly occur in combination with menopausal symptoms, including vasomotor symptoms, sleep and sexual disturbances, and weight and energy changes. These menopausal symptoms can complicate, co-occur, and overlap with the clinical presentation of depression.

Conversely, depression may affect an individual's judgment of the degree of bother from menopausal somatic symptoms, thereby further magnifying the effect of symptoms on quality of life. The interrelationship between depressive symptoms and menopausal symptoms may pose a challenge when attempting to parse out contributing etiologies, relative contributions of each etiology, and the potential additive effects.

Diagnosis and treatment options

Diagnosis involves identifying the menopausal stage, assessing for co-existing psychiatric and menopause symptoms, appreciating the psychosocial factors common in midlife, and considering the differential diagnosis. Validated screening instruments can be helpful. Although a menopause-specific mood disorder scale does not yet exist, several general validated screening measures, such as the Patient Health Questionnaire-9, or PHQ-9, can be used for categorical determination of mood disorder diagnoses during the menopause transition.

Antidepressants, cognitive-behavioral therapy, and other psychotherapies are considered first-line treatments for perimenopausal major depressive episodes. Only desvenlafaxine has been studied in large randomized placebo-controlled trials and has proven efficacious for the treatment of MDD in perimenopausal and postmenopausal women.

A number of small open-label studies of other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine to treat MDD in perimenopausal and postmenopausal women have demonstrated a positive effect on mood, and several SSRIs and SNRIs also have the added benefit of improving menopause-related symptoms.

In women with a history of MDD, a prior adequate response to a particular antidepressant should guide treatment selection when MDD recurs during the midlife years.

Although estrogen is not approved by the US Food and Drug Administration specifically for the treatment of mood disturbances, some evidence suggests that unopposed estrogen therapy has efficacy similar to that of antidepressant medications in treating depressive disorders in perimenopausal women,8-11 but it is ineffective in treating depressive disorders in postmenopausal women. Estrogen therapy also may augment the clinical response to antidepressants in midlife and older women.12,13 The data on combined HT (estrogen plus progestogen) or for different progestogens in treating depressive disorders in perimenopausal women are lacking and inconclusive.

The findings from this expert review panel demonstrate that women in the perimenopausal transition are at increased risk for depressive symptoms, major depressive episodes, and major depressive disorder. The interrelationship between symptoms of depression and menopause can complicate, co-occur, overlap, and magnify one another. Clinicians treating perimenopausal women with depression that is unresponsive to conventional antidepressant therapy should consider concurrent use of estrogen-based hormone therapy or referring the patient to a clinician comfortable doing so.


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