Perimenopausal depression: signs, causes and treatment

Perimenopause is a period of raised risk for depression, including for women who have never been depressed before. Two long-running US studies found women were two to four times more likely to have a major depressive episode during the transition and early postmenopause than beforehand, and the risk is not explained by hot flashes or stress alone. The signs are the same as depression at any age, but they often arrive tangled up with night sweats, broken sleep and irritability, which delays recognition. Treatment works: antidepressants and psychotherapy are first-line, and estrogen has a supporting role for some women. If you are having thoughts of harming yourself, call or text 988 now.

What perimenopausal depression is

The National Institute of Mental Health (NIMH) defines depression by symptoms that last most of the day, nearly every day, for at least two weeks and interfere with daily life. They include persistent sad, anxious or empty mood; irritability; hopelessness or guilt; loss of interest or pleasure; fatigue; trouble concentrating; changes in sleep or appetite; physical aches without a clear cause; and thoughts of death or suicide. The NIMH lists perimenopausal depression as a recognized form, noting intense irritability, anxiety, sadness or loss of enjoyment as common features.

The Menopause Society’s 2018 guidelines, developed with the National Network of Depression Centers, describe midlife depression as classic depressive symptoms commonly combined with menopause symptoms such as hot flashes and sleep disturbance, plus the psychosocial challenges of this stage. They define the window of vulnerability broadly: the early and late menopause transition and the early postmenopause. If you are unsure where you are, see what is perimenopause.

Low mood for a few days, or sadness in response to a loss, is not depression. Two weeks or more of most-days symptoms that change how you function is.

Why it happens in perimenopause

The evidence that the transition itself raises risk comes from studies that followed the same women over years.

In the Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN), 221 women who were premenopausal at entry were interviewed annually with a structured diagnostic interview. They were two to four times more likely to have a major depressive episode when perimenopausal or early postmenopausal than when premenopausal. That held after accounting for a history of depression, upsetting life events, psychotropic medication, hot flashes and measured hormone levels. A history of depression was the strongest predictor across the whole study.

A University of Pennsylvania cohort study followed premenopausal women with no history of depression for eight years. High depressive symptom scores were more than four times as likely during the transition as before it (odds ratio 4.29), and a diagnosed depressive disorder was two and a half times as likely (odds ratio 2.50). The key mechanistic finding was that greater variability in estradiol, FSH and LH around each woman’s own average was linked to depressive symptoms, independent of hot flashes, poor sleep, smoking and body weight.

Put plainly: it is not low estrogen alone that destabilizes mood, it is estrogen that swings. The brain systems that regulate mood are sensitive to estrogen, and perimenopause is the one time in adult life when levels fluctuate unpredictably from month to month. Layer on night sweats, insomnia (see why perimenopause wakes you at 3 a.m.), and the aging parents, teenagers and career pressures typical of the 40s and 50s, and the risk compounds.

The guidelines add one important nuance: most midlife women who have a major depressive episode during perimenopause have had one before. A first-ever episode does happen, as the Pennsylvania study shows, but a prior history is the biggest risk factor.

What else can cause it

Several conditions mimic or feed depression at this age and should be checked:

• Thyroid disease, especially an underactive thyroid, which causes fatigue, low mood and weight gain
• Anemia and vitamin deficiencies
• Sleep apnea, which in women often presents as low mood, fatigue and insomnia; see sleep apnea in women after 40
• Chronic insomnia, which both causes and results from depression; see perimenopause insomnia
• Alcohol and some medications, including certain blood pressure drugs, steroids and hormonal contraceptives
• Bipolar disorder, where periods of unusually high energy or little need for sleep alternate with depression; this changes treatment and should be asked about
• Grief, caregiving strain and relationship or work stress, which are real causes in their own right

The Menopause Society’s guidelines recommend that evaluation include identifying the menopausal stage, assessing co-occurring psychiatric and menopause symptoms, considering psychosocial factors, ruling out other diagnoses and using validated screening questionnaires. A symptom check can help you organize what to report.

What helps, ranked by evidence

Strong: antidepressants and psychotherapy. The guidelines are clear that proven treatments for depression, meaning antidepressant medication and psychotherapy, are the front-line treatments for perimenopausal depression. The NIMH names cognitive behavioral therapy and interpersonal therapy as evidence-based psychotherapies, and notes that antidepressants usually take four to eight weeks to work fully. SSRIs and SNRIs have the added advantage of reducing hot flashes in many women, so one medication may ease both.

Moderate: estrogen therapy in perimenopausal women, especially with hot flashes. Estrogen is not FDA-approved to treat depression, but the guidelines find evidence that it has antidepressant effects in perimenopausal women, particularly those with vasomotor symptoms. The strongest trial is from the University of North Carolina: 172 perimenopausal and early postmenopausal women aged 45 to 60 who were not depressed at the start were randomized to 12 months of transdermal estradiol (0.1 mg/day) with oral micronized progesterone for 12 days every three months, or placebo. Clinically significant depressive symptoms developed in 17.3% of the hormone group versus 32.3% on placebo. The benefit appeared in women in the early transition, not the late transition or postmenopause, and was larger in women who had recently been through stressful life events. Data on estrogen plus progestin for established depression are sparse. See hormone therapy and sleep for risks and who should not use it.

Supporting: treating sleep. Insomnia and depression reinforce each other. CBT-I improved emotional well-being in trials of menopausal women; see CBT-I for menopause insomnia.

Insufficient: botanicals and natural products. The guidelines reviewed natural health products and found the evidence insufficient to recommend them for perimenopausal depression. Exercise has general benefits for mood and health but is not a replacement for treatment of a depressive episode.

For treatment-resistant depression: the NIMH notes brain stimulation therapies and newer medications are options when standard treatments have not worked; these are decisions for a psychiatrist.

When to see a clinician

See a clinician if low mood, loss of interest or irritability has lasted two weeks or more, or sooner if it is affecting work, relationships or caring for yourself.

Get help immediately if you have thoughts of death, suicide or harming yourself. Call or text 988 to reach the Suicide & Crisis Lifeline, or chat at 988lifeline.org. It is free, confidential and available 24 hours a day, every day. In a life-threatening emergency, call 911.

Other reasons to be seen promptly:

• You cannot get out of bed, eat or manage daily tasks
• Periods of unusually high energy, racing thoughts or very little need for sleep, which may point to bipolar disorder
• Hearing or seeing things others do not, or beliefs others find unrealistic
• Heavy alcohol or drug use to cope

An ob-gyn or a clinician found through how to find a menopause specialist can place you in the transition and treat hot flashes and sleep; a primary care clinician or mental health professional can diagnose and treat the depression itself. You do not have to choose. Start with whoever you can see soonest and ask them to coordinate.