Polycystic Ovary Syndrome and the Risk of Premenstrual Disorders: A Nationwide Register‐Based Study in Sweden

<b>Background:</b> Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. It has been linked to a range of psychiatric disorders. Although premenstrual disorders (PMDs) are characterized by psychiatric symptoms in tandem with hormone changes controlled by the endocrine system, the association between PCOS and PMDs remains unknown. <b>Methods:</b> We conducted a nationwide register-based cohort study including 2,965,178 females during 2001-2018 in Sweden. Individuals with PCOS were identified from clinical diagnoses recorded in the Swedish national registers (<i>n</i> = 41,515) and PMDs were identified based on clinical diagnoses and prescriptions with a clear indication of PMDs during follow-up. Using multivariable Cox regression, hazard ratio (HRs) of PMDs were estimated by comparing individuals with PCOS to those without. To account for confounders such as genetics or family environment, we conducted sibling comparison (<i>N</i> = 160,566). <b>Results:</b> During a median follow-up of 15.3 years, 1308 (1.9%) individuals with PCOS had a premenstrual disorder (PMD) (4.67/1000 person-years). Compared to individuals without PCOS they had more than doubled risk of PMDs (age-adjusted HR: 2.26, 95% CI 2.14- 2.39). The association was attenuated after adjustment for demographic and socioeconomic factors as well as for comorbid psychiatric disorders and obesity yet remained significant (HR: 1.54, 95% CI 1.46-1.63). The sibling comparison showed similar findings (full-adjusted HR: 1.61, 95% CI 1.36-1.92). The association between PCOS and PMDs remained statistically significant regardless of the presence of psychiatric comorbidities, with HR of 1.33 (95% CI 1.20-1.47) for individuals with psychiatric comorbidities and 1.55 (95% CI 1.45-1.65) for those without. <b>Conclusions:</b> Our findings suggest that individuals diagnosed with PCOS were at increased risk for PMDs. This association could not be entirely explained by shared risk factors, including such that sisters share.