Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.
BACKGROUND
The risks of testosterone therapy in men remain poorly understood.


OBJECTIVE
The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men.


METHODS
We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies.


METHODS
Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility.


METHODS
Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data.


RESULTS
The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes.


CONCLUSIONS
The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.
Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
M Mercè
MM
Fernández-Balsells
Mohammad Hassan
MH
Murad
Melanie
M
Lane
Juliana F
JF
Lampropulos
Felipe
F
Albuquerque
Rebecca J
RJ
Mullan
Neera
N
Agrwal
Mohamed B
MB
Elamin
Juan F
JF
Gallegos-Orozco
Amy T
AT
Wang
Patricia J
PJ
Erwin
Shalender
S
Bhasin
Victor M
VM
Montori
D000328:Adult; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D003627:Data Interpretation, Statistical; D006801:Humans; D008297:Male; D009026:Mortality; D011086:Polycythemia / Q000139:chemically induced / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000592:standards; D012307:Risk Factors; D013739:Testosterone / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014570:Urologic Diseases / Q000139:chemically induced / Q000453:epidemiology
D013739:Testosterone