Insulin resistance is associated with depression risk in polycystic ovary syndrome

Fertil Steril. 2018 Jul 1;110(1):27-34. doi: 10.1016/j.fertnstert.2018.03.009. Epub 2018 Jun 13.


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.

Keywords: Polycystic ovary syndrome (PCOS); depression; insulin resistance.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Clomiphene / therapeutic use
  • Depression / etiology*
  • Depression / metabolism
  • Female
  • Humans
  • Infertility, Female / drug therapy
  • Infertility, Female / etiology
  • Infertility, Female / metabolism
  • Infertility, Female / psychology
  • Insulin Resistance / physiology*
  • Letrozole / therapeutic use
  • Polycystic Ovary Syndrome / complications*
  • Polycystic Ovary Syndrome / drug therapy
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / psychology*
  • Retrospective Studies
  • Risk Factors
  • Young Adult


  • Clomiphene
  • Letrozole