This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.
Treatment with testosterone (the primary male sex hormone) does not increase the risk of heart attack, stroke or other diseases of the heart and blood vessels (cardiovascular disease), research found. The treatment was safe when given for less than a year to men with low levels of testosterone (hypogonadism). Longer term follow up is ongoing.
Men with hypogonadism can experience loss of muscle mass, sexual problems, and reduced quality of life. Testosterone treatment can successfully address these changes. However, many doctors are reluctant to prescribe this treatment because of concerns about its safety.
In a large analysis of safety data on testosterone treatment, researchers found no evidence that testosterone increased cardiovascular problems in the short- to medium-term. Few men died when receiving treatment. There were no groups (such as elderly men) at increased risk of cardiovascular events such as heart attacks.
An ongoing study by another research group is assessing the long-term safety of testosterone.
More information on hypogonadism is available on the NHS website.
UPDATE (27/12/2023): Further research from the same team found that testosterone treatment improved sexual function and quality of life compared with placebo in men with low serum testosterone (less than 12 nmol/L) but without classic hypogonadism. This was irrespective of age, obesity, or degree of low testosterone. However, researchers said that older men and those with obesity were less likely than others to reach adequate sexual function.
The issue: how safe is testosterone treatment?
Testosterone plays a key role in male physical development and sexual behaviour. A lack of testosterone (hypogonadism) can impact men’s physical health (weakened muscle and bone), appearance (body shape, loss of body hair), sexual function, and quality of life. Men with hypogonadism often start testosterone treatment between the ages of 40 and 65.
There is conflicting evidence on whether testosterone could increase the risk of cardiovascular events such as heart attacks. Testosterone improves blood sugar levels and reduces body fat, which could be beneficial. But other effects, such thickening the blood (increasing the likelihood of blood clots) could potentially increase the risk of problems. Uncertainty about its safety has made many doctors reluctant to prescribe testosterone to men who could benefit from it.
Researchers analysed safety data from multiple studies on testosterone treatment.
What’s new?
This review included studies from 1992 onwards, in which testosterone was compared to a dummy treatment (placebo) in men with testosterone deficiency. Across 17 studies, 1,750 men received testosterone and 1,681 received placebo. Men were 65 years on average; most were White and non-smokers. On average, they were on the border between being overweight and obese (body mass index of 30).
The men in the studies were treated for an average of just over 9 months.
The study found:
- similar numbers with cardiovascular disease in the testosterone (8%) and placebo group (7%)
- similar, low numbers of deaths in the testosterone (0.4%) and placebo group (0.8%)
- the chance of cardiovascular disease was not increased by age, the level of testosterone before treatment, smoking or diabetes status.
Testosterone treatment did not increase blood pressure, blood clots or blood sugar levels. It reduced levels of fat (cholesterol) in the blood compared with placebo.
Why is this important?
Testosterone treatment does not increase the risk of cardiovascular disease in the short- to medium-term, this research found. Few deaths occurred during trials of testosterone. No patient characteristics (such as age) increased the risk of cardiovascular disease. This review used international data, so its findings could apply to men worldwide.
Men in this review were at higher risk of cardiovascular disease than the general population because of their weight, age, and other characteristics (risk factors). Despite this, few developed cardiovascular disease, regardless of whether they received testosterone or placebo.
Clinicians should therefore be reassured that they can prescribe testosterone to men with cardiovascular risk factors without increasing their risk of cardiovascular events (such as a heart attack) in the short- to medium-term. However, men were followed up for just over 9 months on average, and cardiovascular disease can take longer to become apparent.
An ongoing study by another research group is assessing the long-term safety of testosterone. Men will be followed up for 5 years in this research.
What’s next?
As a result of this study, international clinical guidelines are being updated. They state that no short-term increase in adverse events has been seen in men with hypogonadism who are prescribed testosterone and followed up appropriately.
In further work, the researchers are assessing the value for money of testosterone treatment, and whether some groups of men (such as younger men) benefit especially from treatment.
You may be interested to read
This Alert is based on: Hudson J, and others. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longevity 2022; 3:e381–e393.
Updated clinical guidelines on testosterone treatment for men with testosterone deficiency.
A short summary of the study on the Imperial College London website.
Further research by the same team: Hudson J, and others. Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis. The Lancet Healthy Longevity 2023; 4(10): E561-E572.
Research on cost-effectiveness by the same team: Hernández R, and others. Cost-effectiveness of testosterone treatment utilising individual patient data from randomised controlled trials in men with low testosterone levels. Andrology and Humanities 2024; 12(3): 477-486.
Funding: This study was funded by the NIHR Health and Technology Assessment Programme.
Conflicts of Interest: See the full paper for the conflicts of interest.
Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.
