Los Angeles—Testosterone replacement therapy appears to be a mixed blessing for older men with low levels of the hormone, according recently published studies.

Results of four trials published online by JAMA and JAMA Internal Medicine suggest users showed improved bone density and strength, as well as reduced anemia, after 1 year of testosterone therapy. On the other hand, the therapy is linked with a 20% increase in arterial plaque, according to a fifth trial that was not part of the Testosterone Trials (TTrials), and it also appears to have no effect on improving cognitive function.

The TTrials are the largest studies to examine the efficacy of testosterone treatment in men >65 years whose testosterone levels are reduced due to age. Conducted at 12 study sites across the country, 790 participants were given testosterone gel or a placebo applied daily to the skin. Over a year, the National Institutes of Health (NIH)– funded clinical research trial sought to determine if testosterone treatment of men aged >65 years improved their mobility, vitality, sexual function, memory, blood count, and cardiovascular risk.

Cardiac effects ended up being most disturbing, according to the additional study’s researchers who reported that the participants who received a placebo had just a 1% rise in plaque volumes versus 20% for those receiving the actual testosterone treatments for a year.

“Heart disease remains the number one cause of death in the U. S., and measuring coronary artery atherosclerosis has become a most effective method for evaluating cardiovascular risk,” said primary author Matthew J. Budoff, MD, from the Los Angeles Biomedical Research Institute (LA BioMed) an independent non-profit biomedical research organization associated with UCLA. “While physicians are increasingly prescribing testosterone replacement for their older male patients, recent studies had reached conflicting conclusions about the potential cardiovascular risks. This finding of a significant increase in plaque volumes among men undergoing testosterone treatments indicates they may face a potentially increased risk of heart disease. However, longer-term research is needed to determine the actual risk.”

Here are the key findings of the TTrials, published at the same time:
• Anemia trial: After one year of treatment with testosterone, 54% of the men with unexplained anemia and 52% of those with anemia from known causes had clinically significant increases in hemoglobin levels, compared with 15% and 12%, respectively, of those in the placebo group.
• Bone trial: After 1 year of testosterone treatment, participants significantly increased volumetric bone mineral density and estimated bone strength compared to controls, with results greater in the spine than the hip.
• Cognition trial: After 1 year, there was no significant change in either the treatment or the placebo group in cognition, as measured by verbal memory, visual memory, executive function, and spatial ability.
• Cardiovascular outcomes trial: Among men as young as 40 with low testosterone, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of about 3 years in an observational study.
These are the second set of results from the long-term TTrials, which demonstrated the benefit of testosterone therapy on sexual function in older men with low testosterone in a report published last year.

“Looking globally at testosterone therapy, the strongest evidence is for sexual function,” said Thomas Gill, MD, a lead author from Yale University.

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