Testosterone Replacement Trials Proceed Slowly

(part 2 of 2 posts)

Alerting men to screening and treatment for low testosterone may get them in to their doctors faster, but they may be astounded to learn that the science in the field is wanting. The National Institute of Aging only enrolled its first patient in a testosterone replacement trial a little over a year ago, according to Peter Snyder, MD, principal investigator of the trial, and endocrinologist at the University of Pennsylvania, Philadelphia.”You can’t make any conclusions about whether it does any good,” said Snyder, who added that in 2003, an Institute of Medicine Panel urged systematic study in older men and recommended against “widespread, generalized use to prevent possible age-related diseases or for enhancing strength or mood in otherwise healthy older men.”

On the day that the report was released, a New York Times editorial titled “The Testosterone Gamble” opened with this question: “Can American men be rushing into the same reckless use of hormones that brought grief and anxiety to so many unsuspecting women?”

Although proponents of testosterone liken testosterone levels declining in a similar fashion to female menopause and refer to “male menopause” or “andropause,” the IOM Committee concluded that there is “scant evidence” for a shutdown like there is among women. In fact, the Committee concluded that supplements “are only appropriate for indications approved by the FDA (the primary indication is hypogonadism in men who make little or no testosterone.)”

The Committee is not alone in this assessment: many physicians told me that they worry that men will use testosterone replacement therapy before studies of effectiveness, benefits, and any problems are known.

Research Priorities

The wheels of science proceed slowly, perhaps too slowly for those who want to try the latest drug. Without rigorous study, there could be harm. In fact, some research has raised concerns about testosterone accelerating prostate cancer and an enlarged prostate (BPH); one  study was halted because of heart effects.

The IOM Committee pressed for studies that would show whether testosterone is an effective treatment in men with low testosterone levels. Unless a clear benefit is demonstrated, the Committee urged not proceeding to studies of long-term risks.

A top priority is to test testosterone replacement among men age 65 and older whose testosterone levels are below the physiologic levels of young adults. These would be randomized, short-term, placebo-controlled randomized trials. Outcomes should be measured in four areas, weakness/frailty/disability; sexual dysfunction; cognitive dysfunction; and well-being/quality of life. If clinically significant benefit is demonstrated in the early trials, long-term studies should follow,according to the Committee. Safety should be assured in all the trials. Further study of age-related changes in testosterone levels should also be done.

The Testosterone Trial

A coordinated set of six trials is being done at 12 sites around the country, under the direction of the National Institute of Aging, according to Snyder. “We are selecting men age 65 and over with unequivocally low testosterone, 275 ngs on two separate early mornings because these are the men we would anticipate might get the most benefit,” said Snyder. Overall, 80 percent of men have values over 275 at 2 separate times.

Testing testosterone replacement in men age 65 and over is in contrast to the advertising, which focuses on men age 45 and over. “We have strict entry criteria so that men have a very low risk for prostate cancer and at least one of the following conditions: anemia, decreased physical function, low vitality, impaired cognition, or reduced sexual function,” Snyder added. Men in the study either get a testosterone gel (AndroGel/Abbott) or placebo gel to be applied to the torso, abdomen, or upper arms. The testosterone is given first as a loading dose and then adjusted so that the gel brings testosterone into the normal range.

“Of every 100 men who call into our sites, one ends up satisfying enrollment criteria and gets enrolled.” In contrast,  advertising suggests that as many as 38 percent of men age 45 and over have low testosterone and may benefit from treatment.

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