CRD summary

This review concluded that testosterone replacement therapy may have an antidepressant effect, especially for patients who also have hypogonadism or HIV infection. Limitations in the review methods and the evidence base suggest that the conclusions should be treated with caution. The conclusions are unlikely to be applicable to the general population of patients with depression.

Authors' objectives

To evaluate the effect of testosterone administration on depression.

Searching

The authors searched MEDLINE, the Clinical Trials Registry and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to February 2008. The search was limited to English language publications. Search terms were reported. Reference lists were scanned to identify additional studies.

Study selection

Randomised controlled trials (RCTs) comparing testosterone-based treatment with placebo were eligible for the review. Participants had to be diagnosed with a depressive disorder based on diagnostic and statistical manual of mental disorders (DSM) criteria. The primary outcome was depression response, defined as a 50% or greater decrease in Hamilton Rating Scale for Depression (HAM-D) score compared with baseline. Studies that used other scales to assess depression were excluded.

Included trials used a range of different doses and forms of testosterone therapy. Treatment duration ranged from six to 12 weeks. All except one included trial recruited patients with hypogonadism and/or patients who were human immunodeficiency virus (HIV)-positive in addition to being depressed. Two trials included patients with normal testosterone levels at baseline.

Two reviewers independently selected studies for inclusion. Disagreements were resolved by discussion or by consensus of all reviewers.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Data on numbers of participants and outcomes in each group were used to derive the risk ratio and odds ratio (OR) and associated 95% confidence intervals (95% CIs) for depression response. Trial authors were contacted for additional data if necessary.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

Trials were pooled by meta-analysis using a fixed-effect (Mantel-Haenszel) model. Statistical heterogeneity was assessed using the χ² test and I² statistic. Subgroup analyses were performed for patients with and without hypogonadism, those with and without HIV infection, and for different methods of testosterone administration (injection or gel). Publication bias was assessed using the Begg rank correlation method, Egger weighted regression method, calculation of a 'fail-safe N' and examination of funnel plots.

Results of the review

Seven RCTs (n=355 patients) were included in the meta-analysis. Across all trials, testosterone significantly improved depression response compared with placebo (OR 0.40, 95% CI 0.26 to 0.63).

In subgroup analyses, testosterone had a positive effect for patients with hypogonadism and for those with and without HIV infection, but not for those with eugonadism. Testosterone gels were significantly superior to placebo (OR 0.18, 95% CI 0.04 to 0.77, two RCTs) but injections were not (OR 0.54, 95% CI 0.28 to 1.03, four RCTs).

No evidence of significant publication bias was found.

Authors' conclusions

Testosterone may have an antidepressant effect, especially for patients who also have hypogonadism or HIV infection. The route of administration may also affect treatment response.

CRD commentary

The review had clear inclusion criteria for participants, intervention, study design and outcomes. Outcomes had to be evaluated using a particular scale, which meant that relevant studies using other scales would have been excluded. The authors searched a number of relevant sources, but limiting the search to English language studies meant that relevant studies could have been missed (language bias). Unpublished studies were not sought, but publication bias was assessed using standard methods. Two reviewers independently selected studies for the review, but it was unclear whether similar methods to reduce errors and bias were used in data extraction.

The authors did not assess validity of the included trials, which meant that the reliability of the included trials and the synthesis based on them was uncertain. Trials were combined in a meta-analysis; statistical heterogeneity was assessed and differences between trials were investigated using subgroup analyses.

The authors' conclusions reflected the evidence presented, but the lack of validity assessment and small numbers of trials and participants (particularly in the subgroup analyses), suggest that the conclusions should be treated with caution. A high proportion of patients in the included trials had comorbid conditions, such as hypogonadism or HIV infection, and the conclusions are unlikely to be applicable to the general population of patients with depression.

Implications of the review for practice and research

Practice: The authors stated that clinicians may consider evaluating testosterone levels in depressed patients; any testosterone replacement therapy should only be initiated after a thorough discussion of the potential benefits and disadvantages, and the monitoring required.

Research: The authors stated that further trials are required to compare different routes of testosterone administration.

Funding

Charleston Area Medical Center (CAMC) Health Education and Research Institute; CAMC Foundation, Inc., West Virginia.

Bibliographic details

Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. Journal of Psychiatric Practice 2009; 15(4): 289-305. [PubMed: 19625884]

Original Paper URL

http://journals.lww.com/practicalpsychiatry/Abstract/2009/07000/Testosterone_and_Depression__Systematic_Review_and.5.aspx

Indexing Status

Subject indexing assigned by NLM

MeSH

Depressive Disorder, Major /diagnosis /epidemiology; Diagnostic and Statistical Manual of Mental Disorders; Hormone Replacement Therapy; Humans; Hypogonadism /drug therapy /epidemiology; Male; Quality of Life /psychology; Registries; Sexual Behavior /drug effects; Testosterone /adverse effects /therapeutic use

AccessionNumber

12009109209

Database entry date

28/04/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.