SUN-171 - Effects of First-Line PCOS Therapies on Cognitive Function Across Multiple Domains

Background:
The reproductive and cardiometabolic risks associated with polycystic ovary syndrome (PCOS) are well recognized. Current guidelines support management with combined oral contraceptive pills (COCP) and metformin. PCOS is associated with cognitive dysfunction spanning multiple domains however, the effects of first line therapies on cognition remain poorly characterized.

Methods:
We prospectively evaluated neurocognitive outcomes across three treatment arms of the COMET-PCOS trial over 24 weeks. Women with hyperandrogenic PCOS (ages 18-40) and elevated BMI (>25kg/m2) were randomized to low-dose OCP, 2000mg metforminXR, or combination. A comprehensive neuropsychological battery assessing visuospatial construction, visual and verbal memory, psychomotor speed, executive function, attention, and crystallized intelligence was administered at baseline and end of study. Continuous score changes were analyzed using paired t-tests; transitions from deficient to normal range were modeled using GEE-derived odds ratios.

Results:
The mean age of the cohort was 30years, mean BMI was 35kg/m2 and 24% identified as Black. Psychomotor speed showed the most robust and consistent improvements across all three arms. Trails 1 improved significantly in OCP (+7.13, p< 0.001, n=54), metformin (+2.46, p=0.001, n=55), and combined groups (+3.30, p=0.003, n=59). Rey Copy Time pass rates increased significantly in OCP (60.4%→86.8%, OR 4.31, p< 0.001) and combined groups (84.5%→94.8%, OR 3.37, p=0.003). Verbal memory improved significantly across all arms on Logical Memory Immediate and 20-Minute Delay measures (all p< 0.01). Executive function gains were most prominent in the combined arm, with Toolbox Flanker Inhibitory Control improving significantly (+3.52, p=0.002) an effect not seen with either therapy alone. Phonemic Fluency F improved in metformin and combined arms but not OCP alone. Visuospatial construction improved modestly across all arms. Semantic memory and crystallized intelligence showed no significant changes in any arm. No statistically significant between-group differences were identified.

Conclusion:
OCP, metformin, or combined therapy in women with PCOS was associated with broad cognitive improvements, particularly in psychomotor speed and verbal memory, reflecting a combination of treatment benefit and practice effects. To our knowledge this is the first study to comprehensively show that the impact of COCPs and metformin may extend beyond mitigating reproductive and metabolic risks and include a neuroprotective role.

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