Testosterone for Hypogonadism Not Associated With Short- to Medium-Term CV Risk

A systematic review and meta-analysis found no evidence of short- to medium-term cardiovascular risk associated with testosterone use among patients with hypogonadism. These findings were published in The Lancet Healthy Longevity.

Investigators from the University of Aberdeen in the United Kingdom searched publication databases through August 2018 for randomized controlled trials among patients with a screening testosterone level of 12 nmol/L or less who used testosterone for at least 3 months.

A total of 35 studies from 109 publications were included in this analysis. Individual participant data were provided in 17 of the studies (n=3431) and were not provided in 18 (n=2127) of the studies.

Patients were randomly assigned to receive testosterone (n=1724) or placebo (n=1656) and were aged mean 64.5±11.0 and 65.3±10.8 years; 87.5% and 87.6% were White; and 8.4% and 8.6% had a previous myocardial infarction, respectively.

Among the testosterone cohort, the mean duration of treatment was 9.5 months (range, 12 weeks-3 years).

Testosterone treatment was associated with increased testosterone (mean difference [MD], 7.24; 95% CI, 5.07-9.41 nmol/L), free testosterone (MD, 186.40; 95% CI, 115.91-256.90 pmol/L), hemoglobin (MD, 10.87; 95% CI, 8.19-13.55 g/L), and hematocrit (MD, 3.15%; 95% CI, 2.42%-3.88%).

A total of 14 studies reported mortality data, with causes of death including ruptured aortic aneurysm and myocardial infarction. In 3 studies, cause of death was undetermined. Mortality risks did not differ between cohorts (odds ratio [OR], 0.46; 95% CI, 0.17-1.24; P =.13).

A total of 13 studies reported data on cardiovascular or cerebrovascular events. The most common events in the testosterone group were the following:

  • arrhythmia (n=52)
  • heart failure (n=22)
  • coronary heart disease (n=33)
  • myocardial infarction (n=10)
  • stable angina (n=7)
  • aortic aneurysm (n=6)

Cardiovascular and cerebrovascular risk was similar between the 2 cohorts (OR, 1.07; 95% CI, 0.81-1.42; P =.62).

In the 2-stage meta-analysis using combined data, there was no evidence of increased mortality (OR, 0.63; 95% CI, 0.30-1.32; I2, 0%) or cardiovascular or cerebrovascular (OR, 0.96; 95% CI, 0.72-1.27; I2, 0%) risk.

There was no evidence to support an association between testosterone and new-onset diabetes, prostate cancer, hypertension, venous thromboembolism, and nonstroke cerebrovascular pathology.

The major limitation of this analysis was the overall low event rates and paucity of longer-term data.

“Testosterone treatment did not increase cardiovascular event risk in the short term to medium term. Furthermore, we did not identify subgroups with high cardiovascular risk,” the study authors wrote. “However, the current results provide some reassurance about the short-term to medium-term safety of testosterone to treat male hypogonadism.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Hudson J, Cruickshank M, Quinton R, et al. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longev. Published online June 1, 2022. doi:10.1016/S2666-7568(22)00096-4