There is a risk of slighly increased blood pressure, it says, but an Australian expert says men should be reassured.
The FDA has recommended that boxed warnings relating to increased adverse cardiovascular events be removed from testosterone products.
The recommendations come after the 2023 TRAVERSE trial showed no increased risk of major adverse cardiac events in men who took testosterone for hypogonadism, including in those who had pre-existing or high risk of cardiovascular disease.
But the FDA also said a new warning should be added regarding a risk of increased blood pressure for testosterone, after ambulatory blood pressure studies showed an increase in blood pressure with the use of all testosterone products.
Australian endocrinologist Associate Professor Carolyn Allan, from Monash Health, said the results of the TRAVERSE trial were reassuring.
“The take-home message from TRAVERSE is that there is no increase in cardiovascular disease in a group of men at very high risk,” Professor Allan said.
“But some of the more detailed blood pressure studies have raised a question about whether oral testosterone in particular may lead to a very slight increase in systolic blood pressure.”
The oral formulation of testosterone previously listed on the PBS was withdrawn from the Australian market in 2023, she said.
Professor Allan said some ambulatory blood pressure studies had shown a 2-4mmHg increase in systolic blood pressure in men who took oral testosterone.
“There is some suggestion that perhaps men who have an increase in hematocrit, an increase in red blood cells which we know testosterone can lead to, seem to be more prone to that effect, as well as men who already had high blood pressure.
“That is a minor effect, and the question is whether it is a class effect.”
Professor Allan said product information for testosterone preparations available in Australia currently included precautions about use of the product in patients with heart failure, ischaemic heart disease and high blood pressure.
In Australia, men can be prescribed testosterone if they have underlying testicular or pituitary conditions or are aged at least 40, in certain clinical circumstances, she said.
Professor Allan is a member of the Testosterone Treatment and Lifestyle Program for Type 2 Diabetes (T4DM) research group. The T4DM study included 1000 men who were obese with pre-diabetes and low testosterone levels.
“Our primary outcome was prevention of progression to type 2 diabetes in men at high risk of diabetes,” she said.
“All the men underwent a lifestyle program and half the men had intramuscular testosterone. Those who received testosterone were significantly less likely to have diabetes at the end of the two-year study.
“We looked at a number of cardiovascular parameters, blood pressure included, and we didn’t see a change in blood pressure, but that was just a single blood pressure measure when men came along to the study centre.”
Professor Allan said up to one in 200 Australian men had low testosterone and those men should be reassured that testosterone replacement therapy was safe and effective.
It’s also estimated that one in 600 men in Australia have Klinefelter syndrome – an extra X chromosome – leading to small testes, low testosterone and infertility, but many remain undiagnosed, she said.
“We want GPs to screen men if they think they may be at risk of low testosterone. We want them to examine their patients, if appropriate, to find if they’ve got small testes to make a diagnosis. Not all men with low testosterone will have small testes, but men with small testes will almost certainly have some concern about their pituitary testicular axis.
“We want GPs to be out there making the diagnosis, and we want them to be confident that if you are diagnosing a man with a low testosterone level, that when you treat him with testosterone it is quite safe to do so because we are replacing a missing or deficient hormone.”
Professor Allan said testosterone levels often declined as men aged, but this was often driven by other medical conditions, mainly obesity.
“We now know that if men have their obesity treated, often their testosterone levels will improve,” she said.
“Maintaining good general health is the best way for men to preserve their testosterone levels as they age.”
