Highlights
- •Few studies have evaluated the risk of stroke among testosterone-treated men.
- •Existing studies have methodological limitations which preclude valid conclusions.
- •The association between testosterone and the risk of stroke in men remains unclear.
Abstract
In recent years, questions have been raised regarding the cardiovascular safety of
testosterone replacement therapy (TRT). The objective of this study was to systematically
review the available evidence on TRT safety in men, specifically with respect to the
risk of stroke. We identified publications from MEDLINE, EMBASE, and the Cochrane
Central Register of Controlled Trials up to May 2017. Articles eligible for review
included observational studies evaluating TRT and the risk of stroke among men aged
18 or older. Randomized controlled trials (RCTs) comparing testosterone to placebo
in men were also eligible, provided stroke was identified as an adverse event. Among
seven cohort studies of hypogonadal men, one study reported that TRT was associated
with a significant decrease in the risk of ischemic stroke (hazard ratio (HR) 0.64;
95% confidence interval (CI) 0.52–0.80). Another reported a similar decrease in risk
(HR 0.64; 95% CI 0.43–0.96) among treated men who achieved normalized levels of testosterone.
Limitations in study design, including immortal time bias and residual confounding,
may have influenced both of these results. The remaining observational studies did
not report measures of association to estimate the independent risk of stroke associated
with TRT. Among eight RCTs, a low frequency of stroke events (<5) was observed across
both testosterone and control groups, thus precluding any definitive conclusions.
Based on these findings, the association between TRT and the risk of stroke in men
remains unclear, and further large and methodologically robust studies are needed
to establish this relationship.
Keywords
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Article info
Publication history
Published online: August 30, 2017
Accepted:
August 29,
2017
Received in revised form:
August 25,
2017
Received:
August 7,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
