Testosterone and Depression in Men

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Testosterone produced a small average improvement in depressive symptoms across 27 placebo-controlled trials covering 1,890 men (Walther and colleagues, JAMA Psychiatry, 2019). The pooled effect size was 0.21, and the authors found larger effects at higher doses. Most of those trials measured mood as a secondary outcome, and the authors called for trials designed with depression as the primary endpoint.

Men with depression that hasn't responded to treatment often ask about testosterone, frequently after reading that low testosterone mimics depression. Some of them do have low testosterone, and finding it matters. The evidence supports checking for it and treating it when it's confirmed. It does not support testosterone as an antidepressant for men with normal levels.

What the trials show

The pooled data show a small effect. In the 2019 meta-analysis, men receiving testosterone were more likely to show an antidepressant response than men receiving placebo (odds ratio 2.30), and dropout did not differ between groups. The trials varied widely in dose, population, and outcome measures, so the average likely blends men who benefited with men who did not.

In men with confirmed low testosterone, mood improves modestly. The Testosterone Trials enrolled 790 men aged 65 and older with low levels; after a year, men on testosterone reported slightly better mood and lower depressive symptom severity (Snyder and colleagues, New England Journal of Medicine, 2016). The TRAVERSE depression study followed men aged 45 to 80 with two fasting levels below 300 ng/dL and found modest but significant improvements in mood and energy, with no change in sleep or cognition (Bhasin and colleagues, Journal of Clinical Endocrinology & Metabolism, 2024).

The broader reviews are cooler. An individual-patient meta-analysis of 17 trials and 3,431 men found improvements in sexual function and quality-of-life scores, without a significant change in depressive symptoms on the Beck Depression Inventory (Hudson and colleagues, Lancet Healthy Longevity, 2023). The American College of Physicians' 2020 evidence review concluded testosterone had little to no effect on depressive symptoms in men with age-related low testosterone.

Read together, these studies are broadly consistent with a modest benefit concentrated in men whose testosterone is genuinely low, and little benefit for men whose levels are normal.

Testosterone in treatment-resistant depression

Four randomized trials have tested testosterone in men whose depression had not responded to antidepressants or who met criteria for major depression. Their results do not line up.

• Pope and colleagues, 2003 (American Journal of Psychiatry): 22 men with refractory depression and low or borderline testosterone added testosterone gel or placebo to their antidepressant for eight weeks. The testosterone group improved more on clinician-rated depression scales, though not on self-report.
• Pope and colleagues, 2010 (Journal of Clinical Psychopharmacology): a larger trial of 100 men with low testosterone and partial or no response to a serotonergic antidepressant. Testosterone gel did no better than placebo, and the authors concluded it "is not generally effective for depressed men."
• Seidman and colleagues, 2001 (Journal of Clinical Psychiatry): 30 hypogonadal men with major depression received weekly testosterone injections or placebo as monotherapy. Depression improved similarly in both groups; sexual function improved with testosterone.
• Seidman and colleagues, 2005 (Journal of Clinical Psychopharmacology): 26 men with SSRI-resistant depression, mostly with normal testosterone levels, received injections or placebo added to their SSRI. Response was 53.8% with testosterone and 23.1% with placebo, a difference that did not reach statistical significance in a trial this small.

In other words, the one positive trial was the smallest, and the largest was null. Testosterone has not earned a place among the established augmentation options for treatment-resistant depression, such as lithium, thyroid hormone, or an atypical antipsychotic, which the treatment-resistant depression page covers. Where it does belong is in the workup: low testosterone is one of several medical contributors worth finding before concluding that depression is truly resistant.

Who should have testosterone checked

I check testosterone in men with persistent depression who also report low libido, erectile dysfunction, or fatigue that seems out of proportion to their mood. Those symptoms overlap with depression and with antidepressant side effects, which is exactly why a lab value helps.

A single low result is not a diagnosis. Testosterone varies through the day and from one day to the next, so the American Urological Association recommends two early-morning total testosterone measurements and treats a level below 300 ng/dL as a reasonable cut-off (Mulhall and colleagues, Journal of Urology, 2018). The Endocrine Society likewise requires symptoms together with consistently low morning levels before treatment.

How I use it

When hypogonadism is confirmed, I prescribe testosterone and manage the monitoring myself, alongside the depression treatment. The goal is correcting a measured deficiency, with the antidepressant plan continuing in parallel. I don't prescribe testosterone as an antidepressant to men whose levels are normal; the trials don't support it, and the risks below apply regardless of the reason it's prescribed.

Monitoring follows the urology and endocrine guidelines: hematocrit, because testosterone raises red cell counts; PSA in men over 40; blood pressure; and a check that levels land in the intended range. Depression outcomes are tracked with the same rating scales I use for any treatment change, so it's clear whether mood actually moved.

The risks

Testosterone is approved by the FDA for men with a deficiency or absence of their own testosterone. Its labeling states that safety and efficacy in age-related hypogonadism have not been established, and depression is not an approved indication.

• Heart and blood vessels. In TRAVERSE, 5,246 men with low testosterone and cardiovascular risk were followed on testosterone gel or placebo. Major cardiovascular events were similar (7.0% vs 7.3%), while atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%), and pulmonary embolism (0.9% vs 0.5%) were more common with testosterone (Lincoff and colleagues, New England Journal of Medicine, 2023, and current FDA labeling).
• Blood pressure. In February 2025 the FDA added a class-wide warning about blood pressure increases to testosterone labeling, alongside the TRAVERSE results.
• Red blood cells. Testosterone raises hematocrit, and high levels increase clotting risk. This is the most common reason to adjust the dose.
• Fertility. Testosterone suppresses sperm production. The American Urological Association advises against prescribing it to men who are trying to conceive.
• Prostate. PSA monitoring is part of treatment for men over 40.

Who this practice fits, and when to go elsewhere

This fits men whose depression has not responded as expected and who have symptoms that suggest low testosterone, especially when no one has checked. It also fits men already on testosterone from another prescriber whose mood hasn't improved and who want the depression evaluated on its own terms.

Some situations belong elsewhere. Men planning a pregnancy soon should see a urologist or reproductive specialist about alternatives that preserve fertility. A history of prostate cancer, or an abnormal PSA, warrants urology involvement first. Men with normal testosterone who want it as an antidepressant are better served by the established options, and I'll say so at the first visit. An active suicidal crisis needs an emergency department today.

Cost and booking

The practice is out-of-network with all insurance plans. You pay directly and receive a superbill to submit for reimbursement; many NYC plans with out-of-network benefits reimburse a meaningful share of the fee once the deductible is met. The numbers are laid out at fees and out-of-network costs. Laboratory testing is billed separately by the lab, usually to your insurance.

Bring your medication history with doses, and any prior testosterone or other lab results. Schedule a consultation.

Related

Treatment-resistant depression · Depression · Medication management · Second opinions · Ketamine for depression

When Depression Becomes an Emergency

Depression that has resisted treatment carries elevated suicide risk, and starting or changing any treatment, testosterone included, is a time to watch mood closely. If you are not in immediate crisis but are having suicidal thoughts, that warrants same-day or next-day psychiatric evaluation rather than a wait-and-see approach.

Frequently Asked Questions

Does testosterone help depression in men?

On average, a little. A 2019 JAMA Psychiatry meta-analysis of 27 randomized trials found a small reduction in depressive symptoms (Hedges g 0.21), and most of those trials did not have depression as their main outcome. The benefit is clearest in men with confirmed low testosterone, where large trials found modest improvement in mood and energy.

Can testosterone treat treatment-resistant depression?

The evidence is mixed. A 2003 trial of 22 men with low or borderline testosterone found improvement when testosterone gel was added to an antidepressant; a larger 2010 trial of 100 men found no difference from placebo. Testosterone is reasonable when resistant depression coexists with confirmed hypogonadism, and it should not replace established augmentation strategies.

Should men with treatment-resistant depression have testosterone checked?

Yes, when there are symptoms that suggest low testosterone, such as low libido, erectile dysfunction, or fatigue out of proportion to the depression. Diagnosis requires two early-morning total testosterone measurements; the American Urological Association treats below 300 ng/dL as a reasonable cut-off.

Can testosterone replace an antidepressant?

No. Testosterone is approved for hypogonadism, and the trials do not support it as a stand-alone treatment for depression. When I prescribe it for confirmed low testosterone, depression treatment continues alongside it.

Is testosterone safe for the heart?

In the TRAVERSE trial of 5,246 men (2023), testosterone did not increase major cardiovascular events compared with placebo (7.0% vs 7.3%). It was associated with more atrial fibrillation, acute kidney injury, and pulmonary embolism, and FDA labeling now includes a warning about blood pressure increases. Those risks are why treatment requires monitoring.

Will testosterone affect fertility?

Yes. Testosterone therapy suppresses sperm production, and the American Urological Association advises against prescribing it to men who are trying to conceive. Men planning a pregnancy in the near future should discuss alternatives before starting.

Sources

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2. Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160(1):105–111. PMID 12505808
3. Pope HG Jr, Amiaz R, Brennan BP, et al. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol. 2010;30(2):126–134. PMID 20520285
4. Seidman SN, Spatz E, Rizzo C, Roose SP. Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. J Clin Psychiatry. 2001;62(6):406–412. PMID 11465516
5. Seidman SN, Miyazaki M, Roose SP. Intramuscular testosterone supplementation to selective serotonin reuptake inhibitor in treatment-resistant depressed men: randomized placebo-controlled clinical trial. J Clin Psychopharmacol. 2005;25(6):584–588. PMID 16282843
6. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–624. PMID 26886521
7. Bhasin S, Seidman S, Travison TG, et al. Depressive syndromes in men with hypogonadism in the TRAVERSE trial: response to testosterone-replacement therapy. J Clin Endocrinol Metab. 2024;109(7):1814–1826. PMID 38205962
8. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107–117. PMID 37326322
9. Hudson J, Cruickshank M, Quinton R, et al. Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis. Lancet Healthy Longev. 2023;4(10):e561–e572. PMID 37804846
10. Diem SJ, Greer NL, MacDonald R, et al. Efficacy and safety of testosterone treatment in men: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2020;172(2):105–118. PMID 31905375
11. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432. PMID 29601923
12. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. PMID 29562364
13. U.S. Food and Drug Administration. FDA issues class-wide labeling changes for testosterone products. February 28, 2025. fda.gov