White Matter Microstructure and Cognitive Function in Young Women With Polycystic Ovary Syndrome

CONTEXT Polycystic ovary syndrome (PCOS) is a disorder characterized by insulin resistance and hyperandrogenism, which leads to an increased risk of type 2 diabetes in later life. Androgens and insulin signaling affect brain function but little is known about brain structure and function in younger adults with PCOS. OBJECTIVE To establish whether young women with PCOS display altered white matter microstructure and cognitive function. PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Eighteen individuals with PCOS (age, 31 ± 6 y; body mass index [BMI] 30 ± 6 kg/m(2)) and 18 control subjects (age, 31 ± 7 y; BMI, 29 ± 6 kg/m(2)), matched for age, IQ, and BMI, underwent anthropometric and metabolic evaluation, diffusion tensor MRI, a technique especially sensitive to brain white matter structure, and cognitive assessment. Cognitive scores and white matter diffusion metrics were compared between groups. White matter microstructure was evaluated across the whole white matter skeleton using tract-based spatial statistics. Associations with metabolic indices were also evaluated. RESULTS PCOS was associated with a widespread reduction in axial diffusivity (diffusion along the main axis of white matter fibers) and increased tissue volume fraction (the proportion of volume filled by white or grey matter rather than cerebrospinal fluid) in the corpus callosum. Cognitive performance was reduced compared with controls (first principal component, t = 2.9, P = .007), reflecting subtle decrements across a broad range of cognitive tests, despite similar education and premorbid intelligence. In PCOS, there was a reversal of the relationship seen in controls between brain microstructure and both androgens and insulin resistance. CONCLUSIONS White matter microstructure is altered, and cognitive performance is compromised, in young adults with PCOS. These alterations in brain structure and function are independent of age, education and BMI. If reversible, these changes represent a potential target for treatment.