Insulin resistance is associated with depression risk in polycystic ovary syndrome

Objective: To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). Design: Secondary analysis of data from a multicenter randomized trial. Setting: Multicenter university-based clinical practices. Patient(s): Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. Intervention(s): The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. Main Outcome Measure(s): Demographic, endocrine, and metabolic parameters associated with depression. Result(s): In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28–4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11–4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00–4.16). Conclusion(s): Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.