Bidirectional Association Between Premenstrual Disorders and Psychiatric Disorders

Importance: Premenstrual disorders (PMD) often co-occur with psychiatric conditions and exhibit overlapping symptoms. However, the direction and extent of this association remain poorly understood, particularly beyond major affective disorders. Objective: To investigate whether bidirectional associations exist between PMD and a broad range of psychiatric disorders and conditions. Design, Setting, and Participants: In this cohort study, Swedish nationwide and regional registers were used to identify women diagnosed with PMD from January 1, 2001, to December 31, 2022. Each identified woman was matched to their unaffected full sisters and to 10 unaffected controls. A nested case-control design was used to examine psychiatric disorders diagnosed prior to PMD, and a matched cohort design was used to assess incident psychiatric disorders occurring after PMD. The mean (SD) follow-up was 8.2 (5.8) years. Data were analyzed March 2025 to February 2026. Exposures: Clinical diagnosis of PMD and 14 subtypes of psychiatric disorders. Main Outcomes and Measures: Bidirectional associations were estimated using odds ratios (ORs) and hazard ratio (HRs) with 95% CIs. Results: Among 3 630 028 eligible women followed up for a mean (SD) of 8.2 (5.8) years, 104 972 were diagnosed with PMD (mean SD age, 35.4 8.1 years). Of women with PMD, 50 176 (47.8%) had a previous psychiatric disorder diagnosis, compared with 309 802 (29.5%) of 1 049 720 unaffected controls, representing an approximately doubled risk (OR, 2.41 95% CI, 2.38-2.44). Similarly, women with psychiatric disorders were twice as likely as women without psychiatric disorders to receive a subsequent PMD diagnosis (36.6% vs 21.1%; HR, 2.23 95% CI, 2.19-2.27). In sibling analyses, these bidirectional risks were attenuated but the associations remained (OR, 1.95 95% CI, 1.89-2.01; HR, 1.82 95% CI, 1.74-1.90). The highest bidirectional risks were for depression (OR, 2.19 95% CI, 2.15-2.22; HR, 2.70 95% CI, 2.63-2.76) and anxiety (OR, 2.26 95% CI, 2.22-2.30; HR, 2.43 95% CI, 2.37-2.48), with additional associations for attention-deficit/hyperactivity disorder (OR, 2.01 95% CI, 1.94-2.09; HR, 3.55 95% CI, 3.32-3.80), bipolar disorder (OR, 2.01 95% CI, 1.93-2.10; HR, 3.36 95% CI, 3.07-3.67), and personality disorder (OR, 2.01 95% CI, 1.94-2.09; HR, 3.34 95% CI, 3.00-3.72), but not for schizophrenia (OR, 1.01 95% CI, 0.88-1.16; HR, 1.00 95% CI, 0.59-1.72). Conclusions and Relevance: In this nationwide cohort study conducted in Sweden, bidirectional associations were found between PMD and psychiatric disorders and conditions, highlighting the need for sex- and menstrual cycle-informed care in psychiatry. Further research is needed to understand the underlying mechanisms shared between PMD and psychiatric disorders.