Older men whose low testosterone is restored to normal through gels, patches, or injections have a lower risk of heart attack, stroke, or death from any cause, compared to men who are not treated, scientists, including one of Indian-origin, have found.
The US Veterans Affairs database study of more than 83,000 patients also found that men who were treated but did not attain normal levels did not see the same benefits as those whose levels did reach normal.
"It is the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalise the total testosterone levels," said corresponding author Rajat Barua, assistant professor of medicine at the University of Kansas and his colleagues.
"Patients who failed to achieve the therapeutic range after testosterone replacement therapy did not see a reduction in (heart attack) or stroke and had significantly less benefit on mortality," said Barua, who is also with the Kansas City Veterans Affairs Medical Centre.
The study team looked at data on more than 83,000 men in US with low testosterone, all age 50 or above, who received care in Veteran Affairs between 1999 and 2014.
The researchers divided the men into three clinical groups - those who were treated to the point where their total testosterone levels returned to normal; those who were treated but without reaching normal; and those who were untreated and remained at low levels.
All three groups were "propensity matched" so the comparisons would be between men with similar health profiles.
The average follow-up across the groups ranged from 4.6 to 6.2 years.
The sharpest contrast emerged between those who were treated and attained normal levels and those whose low testosterone went untreated.
The treated men were 56 per cent less likely to die during the follow-up period, 24 per cent less likely to suffer a heart attack, and 36 per cent less likely to have a stroke.
The differences between those who were treated and attained normal levels and those who were treated but did not attain normal levels were similar but less pronounced.
Little difference emerged between those who were treated but did not attain normal levels and those whose low testosterone went untreated, except for a slight benefit in survival for those who were treated.
Barua and colleagues said that they don't know the exact reasons for testosterone's apparent benefits for the heart and overall survival.
Possible explanations, they said, could involve body fat, insulin sensitivity, lipids, blood platelets, inflammation, or other biological pathways.
While the study results do seem to advocate for testosterone replacement therapy, Barua stressed the need for "appropriate screening, selection, dosing, and follow-up of patients to maximise the benefit of testosterone therapy."
The study was published in the European Heart Journal.