Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study

J Psychosom Res. 2012 Mar;72(3):205-13. doi: 10.1016/j.jpsychores.2011.11.014. Epub 2012 Jan 11.


Objective: Low circulating levels of testosterone have been associated with major depression, but there is more limited evidence for differences in patients with anxiety disorders. The use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants is associated with sexual side effects, warranting testing for interactions with testosterone.

Methods: Data are from 722 male and 1380 female participants of The Netherlands Study of Depression and Anxiety (NESDA), who were recruited from the community, general practice care, and specialized mental health care. Depressive and anxiety diagnoses were assessed using the DSM-IV Composite International Diagnostic Interview. To smooth the episodic secretion, the four morning saliva samples per participant and the two evening samples were pooled before testosterone analysis.

Results: Morning median testosterone levels were 25.2 pg/ml in men and 16.2 pg/ml in women, with lower evening levels of 18.2 and 14.1 pg/ml, respectively. Significant determinants of testosterone levels were sex, age, time of the day, use of contraceptives, and smoking status. Female patients with a current (1-month) depressive disorder (effect size 0.29; P=0.002), generalized anxiety disorder (0.25; P=0.01), social phobia (0.30; P<0.001), and agoraphobia without panic disorder (0.30; P=0.02) had lower salivary testosterone levels than female controls. Higher testosterone levels were found in male and female participants using SSRIs than in non-users (effect size 0.26; P<0.001).

Conclusion: Salivary testosterone levels are lower in female patients with a depressive disorder, generalized anxiety disorder, social phobia, and agoraphobia as compared to female controls. SSRIs may increase salivary testosterone in men and women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Agoraphobia / diagnosis
  • Agoraphobia / drug therapy
  • Agoraphobia / metabolism*
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Cohort Studies
  • Contraceptive Agents / adverse effects
  • Contraceptive Agents / metabolism
  • Depression / diagnosis
  • Depression / drug therapy
  • Depression / metabolism*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Male
  • Middle Aged
  • Personality Inventory
  • Phobic Disorders / diagnosis
  • Phobic Disorders / drug therapy
  • Phobic Disorders / metabolism*
  • Psychiatric Status Rating Scales
  • Psychophysiology
  • Saliva
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Sex Factors
  • Smoking / adverse effects
  • Smoking / metabolism
  • Testosterone* / analysis
  • Testosterone* / metabolism
  • Time Factors


  • Antidepressive Agents
  • Contraceptive Agents
  • Serotonin Uptake Inhibitors
  • Testosterone