SAN DIEGO — Testosterone supplementation trims visceral fat, builds skeletal muscle, improves muscle strength, and promotes overall sexual function in healthy older men, according to studies presented at the annual meeting of the Endocrine Society.
The findings from small but well-controlled trials, although not definitive, add credence to the theory that testosterone can have a positive impact on the health and vigor of older, as well as younger, men.
In a cautionary note, however, researchers found an alarming number of adverse effects—some of them severe—in men who received the highest doses of testosterone, 600 mg/wk.
For example, an institutional safety review board cut short the high-dose arm of one study when 10 subjects experienced a total of 147 adverse events, including 12 serious adverse events, halfway into a 20-week trial conducted at Charles R. Drew Medical Center in Los Angeles.
The adverse events included polycythemia, leg edema, and two cases of prostate cancer that may have been indolent prior to the patients' receiving high-dose testosterone.
Despite some encouraging findings, principal investigator Thomas W. Storer, Ph.D., said, “It's very important to tell the public that when you get up to these very high doses, clearly you're going to have problems.”
Dr. Storer's study evaluated the effect of testosterone on muscle mass and strength in 60 healthy men aged 60–75 years and 61 healthy men aged 18–34 years. A long-acting GnRH agonist suppressed endogenous testosterone production in all subjects.
Participants were then randomly assigned to receive weekly testosterone enanthate in intramuscular doses of 25 mg, 50 mg, 125 mg, 300 mg, or 600 mg.
Both older and younger men significantly improved their muscle strength in a dose-dependent fashion, as measured by maximal performance on a leg press. Younger men, but not older men, also significantly increased leg power, the speed with which they were able to perform leg exercises.
In contrast to the many side effects encountered on the 600-mg dose and a substantial number of adverse events in men taking 300 mg, few side effects were seen in men assigned to the 125-mg dose. Yet the men taking the 125-mg dose had impressive gains.
“On average, they gained the equivalent of 10 pounds of lean muscle mass in 20 weeks,” Dr. Storer, an exercise physiologist, said at a press briefing. “You have to train pretty hard to gain 10 pounds of lean mass in 20 weeks.”
“We've gone on record as saying that we think the optimal dose, with the most improvement and the least adverse events, is 125 mg,” he added.
A related Drew University study of men in the same age ranges, directed by Peter Gray, Ph.D., found improvements in overall sexual function, a category including libido, sexual activity, and erectile function. Changes in these parameters were highly correlated with testosterone dose for overall sexual function (P = .0002). Libido improved, but only if men were engaged in a sexual relationship at the onset of the study.
No impact was seen on mood or on performance on visuospatial cognition tests in older or younger men taking testosterone.
Meanwhile, an Australian study examined the impact of testosterone replacement on fat and muscle in 60 nonobese men aged 55 years and older with symptoms of androgen deficiency.
Testosterone replacement therapy did not decrease total body fat or abdominal subcutaneous fat during the yearlong study, reported Carolyn Allan, Ph.D., and colleagues at Prince Henry's Institute of Medical Research at Monash University, Victoria, Australia.
Abdominal visceral fat, however, increased by 16.6% in the placebo group, and decreased by 6.8% in men taking testosterone. Those results represented a significant difference between the groups, according to the invesigators.
“These men were not obese, and yet we saw changes in visceral fat,” suggesting that testosterone replacement may have potential for modifying cardiovascular risk, Dr. Allan said.