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Updated: Feb 8, 2026
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Insulin resistance is associated with depression risk in polycystic ovary syndrome
Eleni A Greenwood1, Lauri A Pasch1, Marcelle I Cedars1
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, San Francisco, California.
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.
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