Longitudinal Follow-up of Reproductive and Metabolic Features of Valproate-Associated Polycystic Ovarian Syndrome Features: A Preliminary Report

Background In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. Methods Women with valproate-associated PCOS and those at risk for PCOS (valproate use ≤6 months) were re-evaluated for PCOS. Results Follow-up (mean 17 months) assessments were completed in 14 women (5 with treatment-emergent PCOS, 9 on valproate ≤6-month). Of seven women who developed valproate-associated PCOS, PCOS reproductive features remitted in three of four discontinuing valproate and persisted in all 3 continuing valproate. Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS features remitted (p = 0.01). There was a trend toward lower serum testosterone (p = 0.06). Body-weight and polycystic ovarian morphology did not change. Conclusions In the first longitudinal bipolar-disorder study of valproate-associated PCOS, most valproate-discontinuers had improved reproductive features of PCOS despite static body-weight.