Can hypogonadism (low testosterone) contribute to the development of depression?

The Relationship Between Low Testosterone and Depression

Yes, low testosterone (hypogonadism) can contribute to the development of depression in men, as evidenced by clinical guidelines and research showing a significant association between testosterone deficiency and depressive symptoms. 1, 2

Testosterone Deficiency and Depression: The Evidence

The American Urological Association guidelines specifically identify depression as one of the patient-reported symptoms associated with low testosterone, along with reduced energy, reduced motivation, poor concentration, irritability, and other psychological symptoms 1. This connection is further supported by clinical evidence showing:

• Men with hypogonadism commonly experience depressive symptoms as part of their clinical presentation 2
• Testosterone treatment is associated with modest but significant improvements in depressive symptoms in men with low testosterone 1
• A meta-analysis of 5 randomized controlled trials (n=872) demonstrated that testosterone treatment was associated with improvement in depressive symptoms (SMD, −0.19 [CI, −0.32 to −0.05]) 1

Diagnostic Considerations

When evaluating a patient with suspected testosterone deficiency and depression:

• Confirm testosterone deficiency with two separate morning testosterone measurements below 300 ng/dL 1, 2
• Look for other symptoms commonly associated with low testosterone:
  • Reduced energy and endurance
  • Fatigue
  • Poor concentration and memory impairment
  • Irritability
  • Reduced sex drive and erectile dysfunction
  • Changes in body composition 1, 2

Strength of the Association

The relationship between testosterone deficiency and depression appears bidirectional:

• Men with hypogonadism have a higher prevalence of depression compared to eugonadal men 3
  • One study found that hypogonadal men were 1.94 times more likely to have overt depression symptoms compared to eugonadal counterparts 3
• Young men with congenital hypogonadotropic hypogonadism show significantly higher scores on depression scales than age-matched healthy controls 4
• The most recent evidence from the TRAVERSE trial (2024) confirms that depressive symptoms are common in middle-aged and older men with hypogonadism 5

Treatment Implications

For men with both depression and confirmed testosterone deficiency:

• Testosterone replacement therapy (TRT) can improve depressive symptoms, particularly in:

  • Men with mild depression 6
  • Those with more severe testosterone deficiency 6
  • Patients who haven't responded adequately to SSRIs 6

• The TRAVERSE trial (2024) showed that TRT is associated with modest but significant improvements in mood and energy in hypogonadal men with depressive symptoms 5

• Six months of testosterone replacement therapy has been shown to significantly improve depression scores in young men with congenital hypogonadotropic hypogonadism 4

Important Caveats

• The improvement in depressive symptoms with testosterone treatment is generally modest (SMD, −0.19) 1
• Severe depressive symptoms may not respond adequately to TRT alone and may require conventional antidepressant treatment 7
• The relationship is complex because many conditions are independently associated with both depression and testosterone deficiency, including:
  • Medical illnesses (HIV/AIDS)
  • Obesity
  • Stress
  • Smoking
  • Alcohol abuse 6

Clinical Approach

1. In men presenting with depressive symptoms, consider measuring testosterone levels, especially if they have other symptoms suggestive of hypogonadism
2. For men with confirmed testosterone deficiency (<300 ng/dL on two separate morning measurements) and depressive symptoms:
   • Consider a trial of testosterone replacement therapy for at least 3 months 6
   • Monitor for improvement in mood, energy, and other symptoms
   • For severe depression, conventional antidepressant therapy may still be necessary
   • Men already on SSRIs may experience additional improvement with TRT 6

The evidence clearly supports that low testosterone can contribute to depression in men, and addressing the hormonal deficiency may be an important component of treatment for these patients.