A meta-analysis of data from more than 3,400 patients with hypogonadism, from 17 clinical trials, has found little evidence that testosterone treatment increases the risk of cardiovascular events such as arrhythmia, heart attack, and stroke, in the short-to-medium term.
The findings, published in The Lancet Healthy Longevity on the 8th of June, showed that the rate of cardiovascular events was not significantly higher for participants receiving testosterone treatment (7·5%) compared to those taking a placebo (7·2%).
Fewer deaths were reported during testosterone treatment (0·4%) compared to those using a placebo (0·8%), but numbers were too small to establish whether testosterone reduced mortality risk.
Testosterone replacement therapy is the standard treatment for hypogonadism, yet despite being widely used, up until now the cardiovascular safety of testosterone treatment has remained unclear due to inconsistent findings.
Lead author Jemma Hudson, from the University of Aberdeen, explained that most previous clinical studies relied on aggregate data, rather than individual participant data, and have not published details of individual adverse events.
“Prescribing of testosterone for hypogonadism is increasing globally, but conflicting messages about its safety may have led to many patients not receiving the treatment,” Ms Hudson said.
“Ongoing studies should help to determine the longer-term safety of testosterone but, in the meantime, our results provide much-needed reassurance about its short-to-medium term safety.
“Our findings could have important implications for the treatment of men with hypogonadism worldwide.”
Hypogonadism can cause sexual dysfunction, weakening of bones and muscles, and reduced quality of life, and risk factors for the condition include aging (as testosterone levels decline with age), obesity, and diabetes.
The authors conducted a systematic review identifying 35 eligible clinical trials published since 1992, in which 1,750 people received testosterone to treat the condition, and 1,681 were given a placebo.
Only 17 trials provided individual participant data, which revealed that the average length of testosterone treatment was 9.5 months; the average age of participants was 65 years; their average BMI was 30 kg/m2, which is considered obese; and most were white and did not smoke.
A blinded analysis by two independent clinicians enabled the classification of every cardiovascular event, allowing for a more robust analysis of the cardiovascular safety of testosterone treatment.
Surprisingly, patient age, smoking or diabetes status did not affect cardiovascular risk, and the researchers actually found that testosterone treatment significantly reduced serum total cholesterol, high-density lipoprotein, and triglycerides.