Researchers have found that men whose low levels of testosterone were treated with testosterone replacement therapy also experienced a reduced risk of heart attack, stroke and all-cause mortality.
The study, published in the European Heart Journal, utilizes data obtained from the Veterans Affairs database for more than 83,000 patients.
"It is the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the total testosterone levels," the authors write. "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."
Last month, Medical News Today ran a Spotlight feature on the debate surrounding testosterone therapy, with clinicians in conflict on when such treatment is appropriate and what its risks and benefits are.
One aspect of this debate has been whether or not testosterone therapy can be harmful. Earlier this year, the US Food and Drug Administration (FDA) updated testosterone product labels to include a warning about a possible increased risk of heart attack and stroke.
However, due to the large number of patients involved and the length of its long follow-up period, the findings of the new study could be influential.
In the study, a team of researchers examined health outcomes for men with documented low levels of testosterone aged 50 and above who received treatment in Veteran Affairs medical facilities between 1999 and 2014.
The men were categorized into one of three groups:
- Group 1: men who were treated until their testosterone levels returned to normal
- Group 2: men who were treated whose testosterone levels did not return to normal
- Group 3: men who did not receive testosterone replacement treatment whose levels remained low.
Across the groups, the average follow-up period ranged from 4.6 to 6.2 years.
Men successfully treated with testosterone 56% less likely to die during follow-up
The researchers made sure that men with similar health profiles were involved in the study, meaning that fair comparisons could be made between the groups. In addition, the study excluded patients with a history of heart attack or stroke, although it did include patients with existing heart disease.
Between the men in Group 1 whose testosterone levels returned normal and the men in Group 3 whose low testosterone was untreated, a significant contrast in health outcomes was observed. The men who received treatment were 56% less likely to die, 24% less likely to have a heart attack and 36% less likely to have a stroke than those who were untreated.
Similar differences were observed between Group 1 and the men in Group 2 - who received treatment but whose testosterone levels did not return to normal - but not to the same degree as between Groups 1 and 3.
- Testosterone is the male sex hormone
- It is thought to regulate many bodily functions, including bone mass, fat distribution and muscle size and strength
- Testosterone levels naturally decline in men, typically falling by around 1% each year after men enter their 30s.
There was little difference in the health outcomes of Groups 2 and 3, apart from those who received treatment having a slightly reduced risk of all-cause mortality compared with those who were untreated.
The researchers state that the mechanisms behind these effects remain speculative and more research is needed. They suggest that potential factors include body fat, insulin sensitivity, blood platelets, lipids and inflammation.
However, despite the results suggesting that patients could derive benefit from testosterone replacement therapy, co-author Dr. Rajat Barua - of the Kansas City (Mo.) Veteran Affairs Medical Center - says that there must be "appropriate screening, selection, dosing, and follow-up of patients to maximize the benefit of testosterone therapy."
Several clinicians currently believe that if testosterone therapy can benefit a patient - even if an associated medical condition is not apparent - such treatment is justified. The authors of the study state that off-label use of testosterone is a concern, and that testosterone replacement therapy should only be used for men who have an associated medical condition.
Previously, MNT reported on a study of veterans published in JAMA Psychiatry that estimates around 15-17% of war veterans have had post-traumatic stress disorder (PTSD) at some point in their lifetime.