Can testosterone replacement therapy improve energy and mood in a patient with low testosterone levels, in the absence of libido issues?

Testosterone Therapy for Low Testosterone Without Libido Issues

Testosterone replacement therapy provides minimal to no meaningful benefit for energy or mood in men with low testosterone who lack sexual symptoms, and should generally not be initiated for these indications alone.

Evidence for Energy and Vitality Improvements

The American College of Physicians' comprehensive evidence review demonstrates that testosterone therapy produces only minimal improvements in energy and fatigue, with a standardized mean difference of just 0.17 (CI, 0.01 to 0.32) across three RCTs involving 665 men 1. This effect size is classified as "less-than-small" and is clinically insignificant in real-world practice 1.

• The weighted mean improvement in vitality scores was barely distinguishable from placebo, with high-quality evidence showing no substantial benefit for fatigue complaints 1
• These findings indicate that testosterone therapy should not be prescribed primarily for energy or vitality concerns 2

Evidence for Mood Improvements

For depressive symptoms and mood, the evidence is similarly underwhelming:

• Five pooled RCTs (n=872) showed testosterone produced a "less-than-small improvement" in depressive symptoms with an SMD of -0.19 (CI, -0.32 to -0.05) 1
• Critically, none of these trials required depression at enrollment, and most men had minimal depressive symptoms at baseline 1
• The American College of Physicians explicitly states that testosterone has "little to no effect on depressive symptoms, energy and vitality, or cognition" in older men with hypogonadism 2

Quality of Life Considerations

While testosterone showed a small improvement in quality of life scores (SMD -0.33 on the AMS scale), this primarily reflected improvements in sexual function domains rather than energy or mood 1:

• Men moved from "moderate to mild symptom severity" on average, but this 3.3-point difference was driven largely by sexual symptom improvements 1
• The evidence quality was rated as "low-certainty" 1

Clinical Recommendation Algorithm

Step 1: Confirm the diagnosis properly

• Obtain two separate morning (8-10 AM) total testosterone measurements to establish persistent hypogonadism, with levels <300 ng/dL indicating deficiency 2
• Measure free testosterone by equilibrium dialysis and SHBG, especially in men with obesity 2
• Measure LH and FSH to distinguish primary from secondary hypogonadism 2

Step 2: Assess for appropriate indications

• The primary evidence-based indication for testosterone therapy is diminished libido and sexual dysfunction, not energy or mood 2, 3
• The European Association of Urology explicitly recommends against testosterone therapy in men seeking treatment for energy, vitality, or mood in the absence of sexual symptoms 2

Step 3: If patient insists on trial therapy despite lack of sexual symptoms

• Set realistic expectations: explain that improvements in energy and mood are minimal at best, with effect sizes too small to be clinically meaningful 1
• Reevaluate at 12 months and discontinue if no improvement, as continuing therapy without benefit exposes patients to unnecessary risks 2
• Monitor hematocrit (withhold if >54%), PSA in men over 40, and cardiovascular risk factors 2

Critical Pitfalls to Avoid

• Never diagnose hypogonadism based on symptoms alone without confirmed biochemical testing 2
• Never prescribe testosterone for "age-related decline" in energy without documented low testosterone and sexual symptoms 2
• Approximately 20-30% of men receiving testosterone in the U.S. lack documented low testosterone before treatment initiation—this violates evidence-based guidelines 2
• Testosterone therapy is absolutely contraindicated in men seeking fertility preservation, as it causes azoospermia; gonadotropin therapy (hCG plus FSH) should be offered instead 2

Alternative Approaches to Consider First

Before considering testosterone therapy for energy/mood complaints:

• Evaluate for sleep disorders, thyroid dysfunction, anemia, and vitamin D deficiency 2
• Assess for metabolic syndrome and cardiovascular risk factors 2
• Recommend weight loss through low-calorie diets and regular exercise, which can improve testosterone levels in men with obesity-associated secondary hypogonadism 2
• Address depression with evidence-based treatments (SSRIs, psychotherapy) rather than testosterone 4

The Bottom Line

The evidence does not support initiating testosterone therapy in men whose primary complaints are low energy or mood, even when testosterone levels are low. The effect sizes are too small to justify the treatment burden, cost, and potential risks (erythrocytosis, cardiovascular concerns) 1, 2. The patient should be counseled that testosterone is not an effective treatment for these symptoms and that alternative explanations and treatments should be pursued 2.