Testosterone and depressive symptoms among men in the Diabetes Prevention Program

Psychoneuroendocrinology. 2016 Oct;72:63-71. doi: 10.1016/j.psyneuen.2016.06.009. Epub 2016 Jun 15.


Objective: We examined associations between intensive lifestyle intervention (ILS) and changes in testosterone and associations with mood among middle-aged men.

Design: Secondary analysis of men (n=886) participating in the Diabetes Prevention Program which randomized glucose-intolerant, overweight men to ILS, metformin, or placebo between 1996 and 1999.

Main outcome measures: Changes in testosterone between baseline and 1-year follow-up asnd associations of these changes with mood measures (Beck Depression Inventory [BDI-II], Beck Anxiety Inventory [BAI]).

Results: Median baseline testosterone was 10.98nmol/l and 44% (n=385) had testosterone<10.41nmol/l or 300ng/dl. Testosterone increases were greater among men randomized to ILS vs. metformin vs. placebo (1.15nmol/l vs. -0.12nmol/l vs. -0.27nmol/l, p<0.001). The association between changes in testosterone and mood differed by study arm (p<0.001 for interaction); there were no significant associations between changes in testosterone and mood changes among men in the ILS or placebo arms. Among men in the metformin arm, increases in testosterone were significantly associated with decreases in BDI-II (improved depressive symptoms) (β-coefficient -0.2336, p=0.0002) indicating a 0.23 decrease in BDI-II for every 1nmol/l increase in testosterone and decreases in BAI (improved anxiety symptoms) (β-coefficient -0.2147, p=0.0014). Similar patterns were observed for bioavailable testosterone.

Conclusions: Among overweight middle-aged men with glucose-intolerance, ILS increased endogenous testosterone slightly but without significant improvements in mood. Metformin did not increase testosterone, but among metformin users, testosterone increases were associated with improvements in mood. Thus, interventions that increase endogenous testosterone may not also improve mood.

Trial registration: ClinicalTrials.gov NCT00004992.

Keywords: Androgens; Glucose-intolerance; Mood; Testosterone.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Depression / metabolism*
  • Depression / therapy
  • Diabetes Mellitus / prevention & control
  • Follow-Up Studies
  • Glucose Metabolism Disorders / metabolism*
  • Glucose Metabolism Disorders / therapy
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Metformin / administration & dosage
  • Metformin / pharmacology
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Overweight / metabolism*
  • Overweight / therapy
  • Testosterone / metabolism*
  • Weight Reduction Programs / methods*


  • Hypoglycemic Agents
  • Testosterone
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00004992