Perimenopause and Bipolar Disorder

Midlife brings a second peak in bipolar onset, and depression is the main risk for women already diagnosed

STUDY: Radosavljevic J et al, Bipolar Disorders 2026

STUDY TYPE: Systematic review (14 observational studies, narrative synthesis)

FUNDING: Shoppers Drug Mart (Run for Women); Homewood Research Chair in Women’s Mental Health; Research Institute at St. Joe’s

Background

In women, bipolar disorder has two peaks of onset: early adulthood and ages 45 to 54, which overlaps with perimenopause. Postpartum and premenstrual hormone shifts destabilize bipolar disorder, but perimenopause has drawn little research.

The Study

• 14 studies published since 2018, from population cohorts of up to 1.1 million women to small surveys and inpatient cohorts.
• Outcomes included new-onset bipolar disorder, mood course, treatment response, anxiety, quality of life, and hormone therapy.
• Only four studies used standardized menopause staging (STRAW+10), and none followed patients through the transition.

Results

Large cohorts linked menopausal transition to new bipolar disorder:

• In the UK Biobank, first-onset mania was twice as common in the 2 years around the final period as in the premenopausal years (IRR 2.12). Age-matched men showed no increase.
• Women who had a hysterectomy were twice as likely to develop bipolar disorder (aIRR 2.19), and six times as likely in the first year after surgery.
• Menopause before age 40 carried a higher risk than menopause at the typical age.

In women with existing bipolar disorder, depression risk rises around menopause. In a survey of 498 women, 28% of perimenopausal women reported constant depression over the past year, compared with 14% of premenopausal women. Anxiety rose and quality of life fell in that time, but there was no consistent link to mania.

Past hormonal mood problems raised these risks:

• A history of premenstrual syndrome (odds ratio, OR 6.18)
• Postpartum depression
• Premenstrual dysphoric disorder (OR 3)

Postmenopausal status may worsen response to medications, but hormone therapy trials were few and conflicting.

Practice Implications

1. When a woman in her mid-40s presents with first-episode mania, ask about cycle changes and recent hysterectomy.
2. Treat night sweats and insomnia early, since lost sleep can destabilize mood.

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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