ORIGINAL ARTICLETestosterone and Cardiovascular Risk in Men: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials
Section snippets
METHODS
We developed a systematic review protocol (available by request) in collaboration with the members of the Endocrine Society Task Force on Testosterone in Men with Androgen Deficiency. This report adheres to the Quality of Reporting of Meta-analyses standards for reporting systematic reviews of randomized trials.3
Study Characteristics
Figure 1 shows the results of our systematic search. We found 30 eligible trials that enrolled 1642 men, 808 of whom were treated with testosterone.
Methodological Quality
Table 1 provides the methodological characteristics of the included trials. Overall, the included trials had limited reporting of methodological features that protect trials from the introduction of bias. All but 6 trials (20%)9, 12, 17, 19, 24, 26 inadequately reported allocation concealment; 2 had inadequate blinding.25, 37 The median loss to
Principal Findings
The best available evidence suggests small and clinically negligible effects of testosterone use on lipid fractions, blood pressure, and glycemic control in men with different degrees of androgen deficiency. On the basis of the width of the 95% CI, the pooled data are consistent with both a 1-fold decrease and a 4-fold increase in the odds of cardiac events in patients using testosterone.
Limitations and Strengths
A key limitation of this review refers to the extent to which authors did not explicitly report on all
CONCLUSION
Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Large randomized trials that enroll men with and without cardiovascular disease and measure cardiovascular end points are needed to better inform the decision to use long-term testosterone for other indications.
Acknowledgments
We thank Gunjan Y. Gandhi, MD, Theophilus E. Owan, MD, and Laura I. Pelaez, MD, for their assistance with study selection, data collection, and author contact. We are grateful for the ongoing input and advice from the Endocrine Society Task Force on Testosterone in Men with Androgen Deficiency. We extend our gratitude to the research team at the Knowledge and Encounter Research Unit at Mayo Clinic College of Medicine.
REFERENCES (44)
- et al.
Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis
Am J Med
(2001) - et al.
Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement
Lancet
(1999) - et al.
Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age
Am J Med
(2001) - et al.
Testosterone treatment improves body composition and sexual function in men with COPD, in a 6-month randomized controlled trial
Respir Med
(2004) - et al.
Steroid sex hormones for lower limb atherosclerosis. [update of Cochrane Database Syst Rev. 2000;2:CD000188]
Cochrane Database Syst Rev
(2002) - et al.
Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinicalpractice guideline
J Clin Endocrinol Metab
(2006 Jun) - et al.
Estimators of the Mantel-Haenszel variance consistent in both sparse data and large-strata limiting models
Biometrics
(1986) - et al.
What to add to nothing? use and avoidance of continuity corrections in meta-analysis of sparse data
Stat Med
(2004) - et al.
Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials [published correction appears in JAMA. 2006;295:2482]
JAMA
(2006) - et al.
Interaction revisited: the difference between two estimates
BMJ
(2003)
Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery
J Am Geriatr Soc
Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction
Clin Endocrinol (Oxf)
Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men
Int J Androl
Testosterone treatment of men with alcoholic cirrhosis: a double-blind study
Hepatology
Testosterone therapy in obliterating arterial lesions in the lower limbs
Angiology
Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study
Circulation
Testosterone administration to older men improves muscle function: molecular and physiological mechanisms
Am J Physiol Endocrinol Metab
The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men
Horm Res
Testosterone in the treatment of arterial insufficiency of the lower limbs
Scand J Clin Lab Invest Suppl
Randomized placebo-controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy
Clin Endocrinol (Oxf)
Effect of testosterone cypionate on postexercise ST segment depression
Br Heart J
The short-term effects of high-dose testosterone on sleep, breathing, and function in older men
J Clin Endocrinol Metab
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This work was funded by a Mayo Foundation scholarship to Dr Montori and supported by the Department of Medicine, Mayo Clinic College of Medicine.