Longitudinal changes in PCOS-related reproductive and metabolic markers in female patients with bipolar disorder: a six-month observational study

Female patients with bipolar disorder (BD) have a relatively high burden of polycystic ovary syndrome (PCOS)-related reproductive abnormalities. This six-month longitudinal observational study aimed to examine changes in PCOS incidence and PCOS-related reproductive and metabolic markers in drug-naive female patients with BD managed without medication, with valproate (VPA), or with non-VPA mood stabilizers. A total of 72 drug-naive female outpatients with BD were recruited, and 50 patients ultimately completed the six-month follow-up. At the baseline and six-month time points, the menstrual status of each subject was recorded, the levels of sex hormones and routine metabolic indicators were measured, and ovarian ultrasound examinations were performed. The diagnosis of PCOS was carried out according to the Rotterdam criteria. After six months, no statistically significant increase in PCOS incidence was observed in any treatment group. In the No-Drug group, PCOS incidence and related reproductive indicators did not significantly worsen. In the VPA group, PCOS incidence showed a nonsignificant numerical increase, while oligomenorrhea/amenorrhea, anti-Müllerian hormone (AMH), and free androgen index (FAI) increased significantly after follow-up. These findings suggest longitudinal changes in PCOS-related reproductive markers. In this exploratory six-month longitudinal observational study, early-stage female BD patients with relatively mild symptoms did not show a statistically significant increase in PCOS incidence when untreated. VPA treatment was associated with significant increases in oligomenorrhea/amenorrhea, AMH, and FAI, suggesting changes in PCOS-related reproductive markers. These findings support careful reproductive and metabolic monitoring when VPA is prescribed to women with BD, while larger and longer-term studies are needed to clarify the long-term clinical trajectory of these reproductive marker changes.