The linkage is a two-way street, and points the way to better treatment
STUDY: Zhou J et al, JAMA Network Open 2026;9(5):e2611765
STUDY TYPE: Cohort study (nested case-control and matched cohort designs)
FUNDING: Swedish Research Council for Health, Working Life and Welfare; Swedish Research Council; European Research Council; Karolinska Institutet
Background
Premenstrual disorders affect 20–30% of women of reproductive age, causing physical (premenstrual syndrome) and psychological (premenstrual dysphoric disorder) symptoms, or a mix of the two:
- Mood swings, irritability, tearfulness, anxiety, insomnia, fatigue.
- Hot flushes, night sweats, palpitations, bloating, and food cravings. Joint pain, breast tenderness, vaginal dryness, pain on intercourse, and urinary frequency, urgency, or incontinence.
Many psychiatric disorders also worsen in the premenstrual phase, but how much of that worsening is caused by these premenstrual syndromes? This study finds that most disorders have a bidirectional relationship with premenstrual syndromes, but not schizophrenia, and that has important implications for treatment.
The Study
- Swedish nationwide registers identified 104,972 women with a clinical diagnosis of a premenstrual disorder, each matched to 10 unaffected controls; a sibling comparison controlled for shared genetics and family environment.
- A nested case-control design examined whether prior psychiatric illness predicted a later premenstrual disorder diagnosis; a matched cohort design examined whether a premenstrual disorder diagnosis predicted subsequent psychiatric illness.
- Mean follow-up was 8.2 years; 14 psychiatric categories were assessed.
Results
Women with any prior psychiatric diagnosis were about twice as likely to later receive a premenstrual disorder diagnosis (odds ratio 2.41). The relationship ran the other way too: women with a premenstrual disorder were twice as likely to develop a new psychiatric condition over follow-up (hazard ratio 2.23). Both associations held in sibling comparisons, though at a lower magnitude, suggesting genetics and shared environment explain part of the link, but not all of it.
The strongest bidirectional associations were with:
- Depression (odds ratio 2.19 before; hazard ratio 2.70 after premenstrual disorder diagnosis)
- Anxiety (odds ratio 2.26; hazard ratio 2.43)
- ADHD (odds ratio 2.01; hazard ratio 3.55)
- Bipolar disorder (odds ratio 2.01; hazard ratio 3.36)
- Personality disorder (odds ratio 2.01; hazard ratio 3.34)
Schizophrenia was the notable exception: no association in either direction. The authors suspect diagnostic overshadowing — schizophrenia symptoms may eclipse premenstrual disorder recognition — and antipsychotic-related menstrual irregularities may mask premenstrual symptoms.
Practice Implications
- When women present with worsening psychiatric symptoms before menses, track them on a monthly chart, but don’t assume it is all due to the psychiatric disorder. Ask about symptoms of premenstrual syndrome or PMDD. Treating those may alleviate the problem.
- Schizophrenia may be an exception, although the authors cast doubt on whether this is a true outlier.
- SSRIs (fluoxetine, sertraline, and paroxetine) are FDA-approved for PMDD, but they are not safe in bipolar disorder and are not the only option. Check vitamin D and iron, as low levels can worsen this. Other options for premenstrual syndrome and PMDD with backing from large, placebo-controlled trials include:
- Oral contraceptives
- Chasteberry (20 mg qd throughout the month of a clinically tested extract like Ze-440 or BNO-1095)
- Omega-3 fatty acids (300–1,000 mg qd throughout the month)
- Zinc (30–50 mg qd either continuous or just in luteal phase)
- Ginkgo (60–80 mg BID in luteal phase)
- Calcium supplementation (1,000–1,200 mg/day throughout month)
- Cognitive behavioral therapy
- Exercise
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
