How is anxiety related to low testosterone levels treated?

Treatment of Anxiety Related to Low Testosterone

For men with documented low testosterone (<300 ng/dL on two morning measurements) and anxiety symptoms, treat the anxiety directly with anxiolytics, antidepressants, or integrative therapies (yoga, meditation), while considering testosterone replacement therapy only if concurrent sexual dysfunction or other hypogonadism symptoms are present. 1

Primary Treatment Approach for Anxiety

The NCCN Survivorship Guidelines explicitly recommend treating anxiety symptoms with: 1

• Anxiolytics as first-line pharmacotherapy
• Antidepressants (particularly SSRIs such as paroxetine, sertraline, citalopram, or fluoxetine)
• Integrative therapies including yoga and meditation

Role of Testosterone Replacement Therapy

When to Consider TRT for Anxiety

Testosterone therapy should be considered for anxiety only when:

• Total morning testosterone is consistently <300 ng/dL on at least two measurements 1, 2
• Patient has concurrent symptoms of testosterone deficiency beyond anxiety (reduced libido, erectile dysfunction, decreased energy, reduced muscle mass) 2, 3
• No contraindications to testosterone replacement exist 1

Evidence Limitations

The American College of Physicians' 2020 systematic review found that testosterone treatment showed only a less-than-small improvement in depressive symptoms (SMD -0.19), and notably, most men enrolled in these trials did not have baseline depression or anxiety. 1 This suggests testosterone's direct anxiolytic effects are minimal in the general hypogonadal population.

Clinical Algorithm

Step 1: Confirm Low Testosterone

• Obtain two morning total testosterone measurements 2
• Diagnosis requires levels <300 ng/dL on both occasions 2

Step 2: Assess Symptom Profile

• If anxiety is the sole symptom: Treat anxiety directly with anxiolytics/antidepressants 1
• If anxiety occurs with sexual dysfunction, fatigue, or other hypogonadism symptoms: Consider TRT as adjunctive therapy 1, 4

Step 3: Initial Anxiety Treatment

• Start SSRI (paroxetine, sertraline, citalopram, or fluoxetine) 1
• Consider anxiolytics for acute symptom control 1
• Implement integrative therapies (yoga, meditation) 1

Step 4: Consider TRT if Appropriate

• Initiate TRT only when multiple hypogonadism symptoms are present 1, 3
• Monitor response at 3 months 5
• Continue anxiety-specific treatments concurrently 1

Important Clinical Caveats

Subpopulations That May Respond Better to TRT

Research suggests certain patient groups show greater improvement in mood/anxiety symptoms with testosterone: 5

• Men with HIV/AIDS
• Those with mild depression (rather than severe)
• Patients with more severe testosterone deficiency (<150 ng/dL)
• Men not responding to SSRIs alone

Combination Therapy Considerations

SSRIs may increase testosterone levels (effect size 0.26), which could theoretically provide additive benefit, though this finding requires cautious interpretation. 6 Men already on SSRIs who remain symptomatic may experience further improvement after adding TRT. 5

Quality of Life Improvements

The American College of Physicians found testosterone treatment produced a small improvement in quality of life (SMD -0.33 on the AMS scale), but this improvement may be driven primarily by sexual function improvements rather than mood or anxiety reduction. 1

Monitoring and Follow-Up

• Reassess anxiety symptoms at 3 months after initiating any treatment 5
• If TRT is used, measure testosterone levels at each monitoring visit to ensure mid-normal range 7
• Check hematocrit every 3-6 months initially when on TRT 7
• Continue anxiety-specific treatments even if TRT is added 1

Critical Pitfall to Avoid

Do not use testosterone replacement therapy as monotherapy for anxiety in hypogonadal men. The evidence supports treating anxiety with established anxiolytic/antidepressant therapies, with TRT serving as adjunctive treatment only when broader hypogonadism symptoms are present. 1