Testosterone energy and mood: an honest read of the evidence

Testosterone energy and mood evidence points one way for quality of life and another for depression. The TestES evidence synthesis, published as a UK Health Technology Assessment in 2024, found treatment improved quality of life and sexual function in almost all patient subgroups. Walther 2019 in JAMA Psychiatry found a small effect on depressive symptoms, Hedges g 0.21.

Key takeaways

• The TestES evidence synthesis, published by Cruickshank and Brazzelli in Health Technology Assessment in 2024 and funded by the UK National Institute for Health and Care Research, concluded that testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups.
• Hudson 2023 in Lancet Healthy Longevity, using individual participant data from 3,431 men, found improvement in Aging Males’ Symptoms scores and in several SF-12 and SF-36 quality of life subscores.
• Walther 2019 in JAMA Psychiatry, pooling 27 randomized placebo-controlled trials with 1,890 men, found a reduction in depressive symptoms (Hedges g 0.21, 95 percent CI 0.10 to 0.32) and a response odds ratio of 2.30 (95 percent CI 1.30 to 4.06).
• The same Hudson 2023 analysis found no significant improvement on the Beck Depression Inventory, and Li 2020 in the International Journal of Endocrinology found Aging Males’ Symptoms scores improved while IIEF-5 erectile function scores did not.
• The Endocrine Society clinical practice guideline, published by Bhasin and colleagues in 2018, requires symptoms plus consistently low morning fasting total testosterone confirmed on repeat testing, not symptoms alone.

Who does this evidence apply to?

All of it applies to men with confirmed low testosterone. Health Canada’s product monograph for oral testosterone undecanoate, authorized 12 December 2025, requires deficiency to be clearly demonstrated by clinical features and confirmed by two separate validated biochemical assays of morning testosterone, and states the product should not be used to treat non-specific symptoms suggestive of hypogonadism if testosterone deficiency has not been demonstrated. What testing your own case needs is a decision for your doctor or nurse practitioner.

None of it applies to men whose testosterone is normal. Health Canada’s information update of 15 July 2014 advises that testosterone products should not be used in men for non-specific symptoms if laboratory tests have not been done to confirm a low testosterone level and other possible causes for the symptoms have not been excluded. Tiredness and low mood are exactly the non-specific symptoms that sentence is about. For the diagnostic steps themselves, see how low testosterone is diagnosed in Canada.

What does the testosterone energy and mood evidence actually show?

It shows a measurable improvement in general quality of life scores, a small effect on depressive symptoms that one large analysis found and another did not, and no demonstrated benefit for vitality or walking distance in the trials that measured those endpoints directly.

The strongest single line comes from the TestES evidence synthesis, published by Cruickshank and Brazzelli in Health Technology Assessment in 2024, which pooled 35 trials with 5,601 randomized participants, 17 of which supplied individual participant data covering 3,431 men. In the authors’ own words, testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups, without adverse effects on blood pressure, serum lipids or glycaemic markers. That report is a government-funded health technology assessment rather than an industry study.

Figures used on this page

What do the quality of life scales show?

Two different measurement traditions point the same way. Nian 2017 in Andrologia pooled 5 randomized controlled trials with 1,212 patients and found an Aging Males’ Symptoms total score change of -2.96 (95 percent CI -4.21 to -1.71, p less than 0.00001), with improvement in the psychological subscale (-0.89), the somatic subscale (-0.89) and the sexual subscale (-1.29, 95 percent CI -1.75 to -0.83). On that scale a negative number is an improvement, because it counts symptoms.

Hudson 2023 in Lancet Healthy Longevity reached the same conclusion from a stronger evidence base: raw participant-level data from 3,431 men with a median age of 67. It found improvement in the Aging Males’ Symptoms score and in several SF-12 and SF-36 quality of life subscores, and an IIEF-15 total score mean difference of 5.52 (95 percent CI 3.95 to 7.10). The benefit was not dependent on age, obesity, diabetes, or how low the baseline testosterone was.

Two caveats belong with those numbers. Nian 2017 rests on only 5 trials in a lower-profile journal and is support rather than a lead citation. Hudson 2023 reports that men who start with worse symptoms finish at a lower absolute score even though they improve by the same amount.

What about depression?

The best result in favour is Walther 2019 in JAMA Psychiatry, which pooled 27 randomized placebo-controlled trials with 1,890 men and found a significant reduction in depressive symptoms versus placebo, Hedges g 0.21 (95 percent CI 0.10 to 0.32). The response odds ratio was 2.30 (95 percent CI 1.30 to 4.06), and acceptability was no different from placebo (odds ratio 0.79, 95 percent CI 0.61 to 1.01), meaning men were not more likely to drop out. A Hedges g of 0.21 is a small effect. It is real, and it is small.

The best result against is Hudson 2023, which found no significant improvement on the Beck Depression Inventory in the same program of work that found quality of life scores improving.

Why do two good analyses disagree about depression?

Because they asked slightly different questions of different data. Walther 2019 pooled published results from 27 trials across a range of depression measures and populations, and the authors themselves report high heterogeneity, note that the effect held most clearly at higher doses in carefully selected samples, and call for trials with depression as the primary endpoint. Hudson 2023 used individual participant data on one specific instrument, the Beck Depression Inventory, in trials that were mostly designed to study something else.

So the disagreement is less a contradiction than a difference in scope: a broad pooled signal across many scales, versus a null result on one scale in a narrower dataset. Neither analysis studied men recruited because they had depression.

What a reader should take from this is modest and specific. There is some evidence of a small mood benefit in men with confirmed low testosterone, no trial in this evidence base with depression as its primary endpoint, and no basis for choosing testosterone over treatment for a diagnosed depressive illness. That is a conversation for your doctor or pharmacist.

Did testosterone improve vitality and physical function?

No. The Testosterone Trials main paper, published by Snyder and colleagues in the New England Journal of Medicine in 2016, randomized 790 men aged 65 and older with a serum testosterone below 275 ng/dL and symptoms suggesting androgen deficiency to testosterone gel or placebo gel for 1 year. Each man took part in one or more of three trials: Sexual Function, Physical Function and Vitality.

There was no significant benefit for vitality on the FACIT-Fatigue scale. The proportion of men with an increase of at least 50 m in 6-minute walking distance did not differ significantly within the Physical Function Trial, although it did differ when men from all three trials were included, 20.5 percent on testosterone versus 12.6 percent on placebo (P = 0.003). The same paper reports that men on testosterone reported slightly better mood and lower severity of depressive symptoms, which sits alongside the Beck Depression Inventory null from Hudson 2023 rather than cancelling it.

The same program did find sexual benefit. Snyder 2016 reports significantly increased sexual activity on the Psychosexual Daily Questionnaire (P less than 0.001), with increased sexual desire and erectile function, and Cunningham 2016 in the Journal of Clinical Endocrinology and Metabolism found testosterone significantly improved 10 of 12 measures of sexual activity in 470 men aged 65 and older. The detail is in what the trials show on testosterone and erectile function.

Fatigue has many causes. Where does low testosterone fit?

Low testosterone is one possible cause of fatigue among many, and it is not the most common one. That is why the diagnostic rule is built the way it is. The Endocrine Society clinical practice guideline, published by Bhasin and colleagues in the Journal of Clinical Endocrinology and Metabolism in 2018, requires symptoms plus consistently low morning fasting total testosterone confirmed on repeat testing, plus evaluation of the cause. Symptoms alone do not meet the standard, and neither does a single low reading.

The European Academy of Andrology guidelines on functional hypogonadism in males, published in Andrology in 2020, go further for men whose low testosterone has no organic cause: lifestyle modification and weight reduction come first, before testosterone, and organic causes must be excluded.

Put plainly: if tiredness is the whole reason for the question, the work is to find out what is causing it, and testosterone is one thing to rule in or out rather than the default answer.

What the evidence does not show

• No significant improvement on the Beck Depression Inventory. Hudson 2023 in Lancet Healthy Longevity, using individual participant data from 3,431 men across 17 trials, reported this null result alongside its positive quality of life findings.
• No improvement in erectile function on the IIEF-5 in the metabolic population. Li 2020 in the International Journal of Endocrinology, pooling 18 randomized controlled trials with 1,415 patients, found Aging Males’ Symptoms scores improved while IIEF-5 did not.
• No erectile function benefit in the TRAVERSE sexual function substudy. Pencina 2024 in the Journal of Clinical Endocrinology and Metabolism, in 1,161 men with low libido drawn from the 5,204-man trial, found greater improvement in sexual activity but no improvement in erectile function specifically.
• No significant vitality benefit on the FACIT-Fatigue scale in the Testosterone Trials (Snyder 2016), and no significant difference in the proportion gaining at least 50 m in 6-minute walking distance within the Physical Function Trial.
• No improvement in blood pressure or HDL cholesterol, and no significant change in body weight, waist circumference or BMI. Corona 2015 in the European Journal of Endocrinology pooled 59 randomized controlled trials with 3,029 treated and 2,049 controls.

Frequently asked questions

Does testosterone therapy improve energy levels?

The evidence is mixed and depends on what is measured. General quality of life scores improve: the TestES evidence synthesis, published in Health Technology Assessment in 2024 across 35 trials and 5,601 participants, found improved quality of life in almost all patient subgroups. The Testosterone Trials main paper, published by Snyder and colleagues in the New England Journal of Medicine in 2016 in 790 men aged 65 and older, found no significant benefit for vitality on the FACIT-Fatigue scale.

Does testosterone help with depression?

Walther 2019 in JAMA Psychiatry, pooling 27 randomized placebo-controlled trials with 1,890 men, found a small reduction in depressive symptoms, Hedges g 0.21 (95 percent CI 0.10 to 0.32), with a response odds ratio of 2.30. Hudson 2023 in Lancet Healthy Longevity found no significant improvement on the Beck Depression Inventory. No trial in this evidence base was designed with depression as its primary endpoint.

What is the Aging Males’ Symptoms score and did it improve?

The Aging Males’ Symptoms score is a symptom questionnaire with psychological, somatic and sexual subscales that European guidelines reference. Nian 2017 in Andrologia, pooling 5 randomized controlled trials with 1,212 patients, found a total score change of -2.96 (95 percent CI -4.21 to -1.71), where a negative number means fewer symptoms. Hudson 2023 and Li 2020 also reported improvement on this scale.

If I am tired all the time, does that mean my testosterone is low?

Not on its own. Fatigue has many causes, and low testosterone is only one of them. Health Canada’s information update of 15 July 2014 advises that testosterone products should not be used for non-specific symptoms if laboratory tests have not confirmed a low testosterone level and other possible causes have not been excluded. The Endocrine Society 2018 guideline requires symptoms plus confirmed low morning testosterone, not symptoms alone.

Why do different studies give different answers on mood?

They measure different things in different ways. Walther 2019 pooled published results across 27 trials and many depression scales, and its authors report high heterogeneity and note the effect held most clearly at higher doses in carefully selected samples. Hudson 2023 analysed individual participant data on one instrument, the Beck Depression Inventory. A broad signal and a narrow null are not the same claim.

Does this evidence apply to men with normal testosterone?

No. Every figure on this page comes from trials in men with confirmed low testosterone. The European Medicines Agency states that testosterone medicines are licensed in the EU to treat men with abnormally low levels of the hormone and are not approved for use in healthy older men. Health Canada’s product monograph for oral testosterone undecanoate, authorized 12 December 2025, sets the same requirement.

Related reading: what testosterone therapy actually does, by the numbers, what the TRAVERSE trial found and what gets monitored on testosterone therapy.

References

1. Cruickshank M, Brazzelli M, et al. 2024. The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation. Health Technology Assessment. PMID 39248210. DOI: https://doi.org/10.3310/JRYT3981
2. Hudson J, et al. 2023. Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis. Lancet Healthy Longevity. PMID 37804846. DOI: https://doi.org/10.1016/S2666-7568(23)00169-1
3. Nian Y, et al. 2017. Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials. Andrologia. PMID 27389320. DOI: https://doi.org/10.1111/and.12630
4. Walther A, et al. 2019. Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis. JAMA Psychiatry. PMID 30427999. DOI: https://doi.org/10.1001/jamapsychiatry.2018.2734
5. Li SY, et al. 2020. Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis. International Journal of Endocrinology. PMID 33061966. DOI: https://doi.org/10.1155/2020/4732021
6. Snyder PJ, et al. 2016. Effects of Testosterone Treatment in Older Men. New England Journal of Medicine. PMID 26886521. DOI: https://doi.org/10.1056/NEJMoa1506119
7. Cunningham GR, et al. 2016. Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels. Journal of Clinical Endocrinology and Metabolism. PMID 27355400. DOI: https://doi.org/10.1210/jc.2016-1645
8. Pencina KM, et al. 2024. Effect of Testosterone Replacement Therapy on Sexual Function and Hypogonadal Symptoms in Men with Hypogonadism. Journal of Clinical Endocrinology and Metabolism. PMID 37589949. DOI: https://doi.org/10.1210/clinem/dgad484
9. Corona G, et al. 2015. THERAPY OF ENDOCRINE DISEASE: Testosterone supplementation and body composition: results from a meta-analysis study. European Journal of Endocrinology. PMID 26537862. DOI: https://doi.org/10.1530/EJE-15-0262
10. Bhasin S, et al. 2018. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism 103(5):1715-1744. PMID 29562364. DOI: https://doi.org/10.1210/jc.2018-00229
11. European Academy of Andrology. Guidelines on functional hypogonadism in males. Andrology 2020;8(5):970-987. DOI: https://doi.org/10.1111/andr.12770
12. European Association of Urology. Guidelines on Sexual and Reproductive Health, male hypogonadism chapter. 2026 edition, limited update March 2026. https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-hypogonadism
13. European Medicines Agency. Testosterone-containing medicines referral. CMDh position 8 January 2015. https://www.ema.europa.eu/en/medicines/human/referrals/testosterone-containing-medicines
14. Health Canada. Product Monograph, oral testosterone undecanoate capsules. Authorized 12 December 2025. https://pdf.hres.ca/dpd_pm/00082762.PDF
15. Health Canada. Information Update, Possible cardiovascular problems associated with testosterone products. 15 July 2014. https://recalls-rappels.canada.ca/en/alert-recall/information-update-possible-cardiovascular-problems-associated-testosterone-products

This page is educational information, not medical advice. Testosterone is a prescription medication and a controlled substance in Canada. Talk to your doctor or pharmacist about your own situation.