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Cited by 341Hormonal and reproductive studiesTreatment of Major DepressionStress Responses and Cortisol

Testosterone Gel Supplementation for Men With Refractory Depression: A Randomized, Placebo-Controlled Trial

Pope, Harrison G., Cohane, Geoffrey H., Kanayama, Gen, Siegel, Arthur J., Hudson, James I.·2003·American Journal of Psychiatry
DOI 10.1176/appi.ajp.160.1.105
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Abstract

OBJECTIVE: Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65 who had refractory depression and low or borderline testosterone levels. METHOD: Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial. RESULTS: The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone. CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.

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  • Early studies in men suggest testosterone may be effective in treatment-resistant depression and as an adjunct to SSRI treatment.

    “Early studies in men suggest that testosterone may be effective in treatment–resistant depression and as an adjunct to SSRI treatment17.”

    From Neurobiology of resilience (2012) · cites this paper as [17]

  • Lower circulating testosterone levels are often found in individuals with PTSD or MDD.

    “lower circulating levels are often found in individuals with PTSD or MDD16, 17.”

    From Neurobiology of resilience (2012) · cites this paper as [17]

  • Epidemiological data show that women are significantly more vulnerable to developing major depressive disorder and post-traumatic stress disorder than men.

    “epidemiological data showing that woman are significantly more vulnerable to developing these disorders than men 16, 17”

    From Neurobiology of resilience (2012) · cites this paper as [17]

  • Testosterone in males promotes resilience in major depressive disorder and post-traumatic stress disorder.

    “there is evidence that testosterone in males promotes resilience in MDD and PTSD”

    From Neurobiology of resilience (2012) · cites this paper as [17]

  • Improvement in depression on the Hamilton Depression Rating Scale occurs after 6 weeks or 8 weeks of testosterone treatment.

    “Two studies using the Hamilton Depression Rating Scale found an improvement in depression after 6 weeks (75) or 8 weeks (76).”

    From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [76]

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Related

Authors
Pope, H. G., Cohane, G. H., Kanayama, G., Siegel, A. J., & Hudson, J. I.
Affiliations
Harvard University (US)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2003-01-01
Volume
160
Issue
1
Pages
105-111
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.160.1.105
OpenAlex
W2120109795
Cited by
341
References
35
Citations by year
2026: 3 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 15 · 2016: 11 · 2015: 15 · 2014: 13 · 2013: 21 · 2012: 15
FWCI
10.64
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
testosterone gel, testosterone supplementation, treatment-resistant depression, male depression, androgen deficiency, transdermal testosterone, antidepressant effects, benign prostatic hyperplasia, Hamilton Depression Rating Scale
MeSH terms
Adult, Aged, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Gels, Humans, Male, Middle Aged, Testosterone, Treatment Outcome

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