The Mood Shift: Depression During Perimenopause

By Dr. Beverly Huang ND

For many women, the menopausal transition isn’t just about hot flashes or irregular periods—it’s also a time when emotional health can shift dramatically. Depression is more common during perimenopause than most people realize, and it often goes unrecognized.

This article explores why mood symptoms can intensify during perimenopause, how shifting hormones—particularly estrogen—impact the brain, who’s most at risk, and why hormone therapy may play a role in supporting emotional well-being during this critical time.

Why Does Depression Show Up During Perimenopause and Menopause?

Hormonal changes affect not just the body, but the brain—especially regions that regulate mood and emotion. Estrogen, in particular, plays a key role in regulating neurotransmitters like serotonin, dopamine, and norepinephrine. As estrogen levels begin to fluctuate (and eventually decline), its stabilizing effects on brain chemistry are disrupted.

This biological shift makes some women more vulnerable to depression—especially those with a personal or family history of mood disorders, PMS, postpartum depression, or chronic stress.

How Common Is Depression in Perimenopause?

Depression is far more common in perimenopause than most people think. In fact, 45–70% of perimenopausal women experience some form of depressive symptoms, ranging from low mood and irritability to diagnosable major depression.

This isn’t just a response to aging or life stress—it’s often hormonally driven, especially in the years surrounding a woman’s final period.

When Does the Risk Peak?

The most vulnerable window for mood changes is the 24-month period surrounding a woman’s final menstrual cycle—12 months before and 12 months after. This is when hormonal instability is at its highest, and when symptoms like sleep disruption, anxiety, and vasomotor symptoms (hot flashes and night sweats) often intensify.

What Increases the Risk?

While hormonal shifts are at the core, certain factors can amplify the risk of developing depression during this time:

• Women with more severe vasomotor symptoms (VMS)—such as frequent hot flashes and night sweats—are at significantly higher risk for developing depression

• Adverse life events, such as:

  • Divorce or relationship strain

  • Caregiving for aging parents

  • Job stress or unemployment

  • Children leaving home (empty nest)

• History of depression, PMS, or postpartum mood issues

• Chronic insomnia or poor sleep

• Low social support or high perceived stress

It’s not just about hormones—it’s a perfect storm of biological, psychological, and environmental stressors.

Is It Depression—Or Just Hormones?

While emotional ups and downs can be a normal part of the transition, clinical depression is different. It’s persistent, impairing, and affects both body and mind.

Signs to Watch For:

• Persistent sadness or hopelessness

• Loss of interest in activities

• Fatigue or lack of energy

• Changes in sleep or appetite

• Trouble concentrating

• Feelings of guilt, worthlessness, or self-blame

• Aches or pains without a clear physical cause

• Thoughts of death or suicide (in severe cases)

The Estrogen–Serotonin Connection

Estrogen supports mood by influencing serotonin, one of the brain’s key feel-good chemicals. Here’s how it helps:

• Boosts serotonin production by increasing tryptophan hydroxylase, the enzyme that converts tryptophan into serotonin

• Prevents serotonin breakdown by inhibiting monoamine oxidase (MAO), the enzyme that degrades serotonin

• Slows serotonin reuptake, keeping it active longer in the brain

• Enhances serotonin receptor sensitivity, especially 5-HT2A receptors

• Protects serotonin-producing neurons in key mood centers of the brain

When estrogen declines, serotonin levels often drop too, contributing to mood instability, anxiety, irritability, and disrupted sleep.

Hormone Therapy: A Mood-Boosting Option

For some women, transdermal bioidentical estrogen therapy—specifically 17β-estradiol—offers significant antidepressant effects, particularly in perimenopause.

This form of hormone therapy has shown the strongest benefit for mood symptoms during the menopause transition. It can be especially helpful during perimenopause, even while a woman is still getting her period, as this is often when hormone fluctuations are most intense and mood symptoms peak.

In women who don’t respond well to antidepressants alone, transdermal estrogen can be used to augment their effect—especially when mood issues occur alongside vasomotor symptoms or insomnia.

Don’t forget that estrogen must always be given with progesterone for uterine protection in women who still have a uterus.

You’re Not Alone

If you're feeling unlike yourself during perimenopause, know this: you’re not alone, and it’s not “just in your head.” These changes are real, and there are effective ways to support your mental health—without shame, stigma, or silence.

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